4_5886761542598268666.Gastrointestinal liver

Gastrointestinal course hepatic

1. Alcohol and the Liver

Alcohol and the Liver
• There is a broad spectrum of clinical and
laboratory findings in patients with alcoholic
liver disease, ranging from asymptomatic
fatty liver to alcoholic hepatitis to end-stage
liver failure with jaundice, coagulopathy, and
encephalopathy
Loading…
Alcohol and the Liver
• FINDINGS IN ALCOHOLIC LIVER
DISEASE

–moderate alcohol intake appears to have
cardiovascular benefits

– excessive alcohol intake can be associated with
significant social and physical consequences

–for the development of cirrhosis:
•requirement for 80 grams of ethanol daily for 10 to 20
Alcohol and the liver

•In 2009, WHO listed alcohol use as one of the
leading causes of the global burden of
disease and injury, surpassed only slightly by
childhood malnourishment and unsafe sex.


•This placed alcohol use ahead of unsafe water
and sanitation, hypertension, high cholesterol,
and tobacco use, and clearly affirms that
alcohol is the most widely abused substance
Loading…
Alcoholism and the Effects of
Alcohol

•In the United States, approximately 100 000
deaths per year are attributed to alcohol abuse.

•Alcohol use is an underlying cause of more
than 30 conditions and a definite contributing
factor to many more, including
–psychotic disorder
–alcoholic cardiomyopathy
–amnesic syndrome
–alcoholic liver disease.
Alcoholism and the Effects of
Alcohol

•The Mayo Clinic defined alcoholism as a
chronic disease in which the body becomes
reliant upon alcohol (ethanol).

•Furthermore, it has been referred to as a
syndrome that consists of 2 phases:
–problem drinking
and
–alcohol addiction.

Alcoholic Liver Disease
•Beverage Alcohol

–Beer 5%

–Wine 12%

–Hard Liquor 40%
(Brandy, wisky, Rum)

–Arrack 40 – 50%
Alcoholism and the Effects of
Alcohol
•A standard alcoholic beverage has been described as any drink that
contains 14 g of pure alcohol.
•Irrespective of what form of alcohol is consumed, the greatest risk
factor appears to be the quantity of alcohol consumed.
•The definition for low-risk drinking for men and women differs,
because
–women suffer from hepatic damage and cirrhosis with considerably smaller
amounts of alcohol consumption.
–A man should not drink more than 4 drinks per day and no more than 14 drinks
per week.
–A woman should not drink more than 3 drinks per day and no more than 7 drinks
per week.
Risk for the development of ALD
Time to develop ALD = to amount of alcohol
consumed

•Men: 60-80 gm/day for 10 years

•Women: 20-40 gm/day for 10 years


Alcoholic cirrhosis, develops ONLY in 10 to 20% of
those who are chronically heavy drinkers.
Loading…
Risk for the development of ALD
•Epidemiology

–Over 90% of chronic heavy drinkers will develop
steatosis

–10 to 20% will develop alcoholic hepatitis

–ALD cause death of 1 in 50 people in Scotland

–4 fold increase in deaths from ALD in past 30
years
Risk for the development of ALD
•Risk of liver disease
–Amount of alcohol consumed
–Genetic factors
–Female sex
–Obesity
–Chronic viral hepatitis
–Nutritional impairment
–drugs
Alcohol Metabolism and the Liver
•The liver is the principal organ for alcohol metabolism.
•The body naturally recognizes ethanol alcohol as a foreign, toxic
agent that can disrupt normal homeostasis.
•When we consume ethanol, it is rapidly absorbed by the upper
gastrointestinal tract.
•Ethanol is
–diffused throughout the body, but exposure is greatest to the liver, via the
main portal vein.
–metabolized by the body in the gastric mucosa and the liver. These organs
manage an enzyme referred to as alcohol dehydrogenase, which is used by
the body to oxidize ethanol and convert it into acetaldehyde and other
metabolites.
–Acetaldehyde ultimately is converted by the body into acetic acid, and then
acetate. Acetaldehyde affects protein synthesis.
Alcohol Metabolism and the Liver


•Alcohol’s metabolites, especially acetaldehyde, damage vital liver
cells because of the excessive generation of free radicals.


•Excessive amount of this type of free radical causes oxidative
stress, which results in the body’s inability to prevent and repair
hepatic damage and the destruction of deoxyribonucleic acid.
Alcohol Metabolism and the Liver
•In addition to the immediate damage of acetaldehyde and the free
radicals, the phagocytic cells of the liver, the Kupffer cells, also
mount an immune response.
•This response is the result of an increase in toxins in the blood that
leak from the intestinal wall and enter the blood stream because of
alcohol consumption.
•The activation of Kupffer cells is responsible for early ethanol-
induced liver injury that ultimately leads to the death of
hepatocytes.
•This damage results in the manifestation of alcoholic liver disease,
and eventually to the development of fibrosis, or scar tissue, within
the liver.

Alcohol Metabolism and the Liver
•Alcohol metabolism differs dramatically between sexes.
–Women are much more likely to suffer from liver damage than men as a
result of alcohol consumption. However, this phenomenon is not clearly
understood.

•In addition to sex, the incidence of liver damage depends on the
– individual’s ethnicity
–genetic predisposition
–nutritional state.
Alcohol and the Liver
•Physical examination :

–vary from normal to evidence of cirrhosis or
hepatic decompensation
•Abdominal wall collaterals (caput medusa),
•Ascites,
•Cutaneous telangiectasias,
•Digital clubbing,
•Dupuytren's contractures,
•Gynecomastia,
•Jaundice,
•Malnutrition ,
•Palmar erythema,
•Peripheral neuropathy,
Alcohol and the Liver
•Laboratory findings:

–serum AST (SGOT), ALT (SGPT), and
gammaglutamyl transferase (GGT) are often
abnormal in alcoholic liver disease

–disproportionate elevation of serum AST (SGOT)
compared to ALT (SGPT) ratio is usually greater
than 2.0

–absolute values of serum AST and ALT are almost
always less than 500 IU/L
Alcohol and the Liver

–Consumption of alcohol can lead to a variety of
histopathologic changes in the liver ranging from
steatosis to cirrhosis
• Steatosis,
•alcoholic hepatitis,
•cirrhosis

–The mechanism behind the development of ALD is not
completely understood, because it is estimated that
only 10% to 20% of alcoholics develop cirrhosis.

Alcoholic Liver Disease
•Signs and symptoms
–Steatosis:
•usually asymptomatic, hepatomegaly

–Alcoholic hepatitis:
•malaise, jaundice, tender hepatomegaly, fever, weight
loss, abdominal discomfort

–Cirrhosis:
•similar to other causes of cirrhosis.
•Hepatomegaly, splenomegaly, malaise, jaundice, weight
loss, ascites, signs of CLD
Alcoholic Liver Disease and
Alcoholic Cirrhosis
•Hepatic steatosis;

–commonly referred to as fatty liver, is a frequent diagnosis that is not
exclusive to patients suffering from ALD.

–Fatty liver is the accumulation of triglycerides in the hepatocytes.

–Fatty liver has been demonstrated in 90% to 100% of all heavy drinkers.

–Short-term exposure to 80 g of alcohol (about 8 beers) over several days can
produce hepatic changes consistent with fatty liver disease.

–Fatty liver may develop after a single large binge and does not predict progression to
hepatitis
Alcohol and the Liver
•ALCOHOLIC FATTY LIVER:
–Fatty liver disease can be reversed if alcohol
consumption is stopped or significantly reduced.
–progression to fibrosis or cirrhosis occurred only in
patients who continued to ingest alcohol

–there are often no clinical symptoms, so fatty
liver may be undiagnosed. The only
complaint may be mild tender
hepatomegaly.

Alcohol and the Liver
•ALCOHOLIC FATTY LIVER:
•Pathology:
– macrovesicular fatty infiltration
–inflammatory changes are minimal
–fatty liver is not pathognomonic of ethanol ingestion:
• starvation,
•fatty liver of pregnancy,
•drug toxicity (valproic acid, tetracycline,
•antiviral agents such as zidovudine and dideoxyinosine),
•nonalcoholic steatohepatitis,
•viral hepatitis, particularly hepatitis C virus,
•Reye's syndrome,
•inborn errors of metabolism (such as defects in mitochondrial beta
oxidation)
Alcoholic Liver Disease and
Alcoholic Cirrhosis
•Alcoholic hepatitis
–fatty liver with the development of hepatitis, referred to as steatohepatitis, has
been acknowledged as a precursor for the development of cirrhosis.

–Alcoholic hepatitis results directly from alcohol abuse and is observed in as
many as 35% of heavy drinkers.

–Like other forms of hepatitis, alcoholic hepatitis can be subclinical.

–Laboratory findings are more predictive if the disease has progressed.

–Approximately 40% of patients with alcoholic hepatitis who continue to
drink will develop alcoholic cirrhosis within 1 to 2 years.
Alcohol and the Liver

•ALCOHOLIC HEPATITIS:

2. Alcohol and the Liver

Alcohol and the Liver
• There is a broad spectrum of clinical and
laboratory findings in patients with alcoholic
liver disease, ranging from asymptomatic
fatty liver to alcoholic hepatitis to end-stage
liver failure with jaundice, coagulopathy, and
encephalopathy
Loading…
Alcohol and the Liver
• FINDINGS IN ALCOHOLIC LIVER
DISEASE

–moderate alcohol intake appears to have
cardiovascular benefits

– excessive alcohol intake can be associated with
significant social and physical consequences

–for the development of cirrhosis:
•requirement for 80 grams of ethanol daily for 10 to 20
Alcohol and the liver

•In 2009, WHO listed alcohol use as one of the
leading causes of the global burden of
disease and injury, surpassed only slightly by
childhood malnourishment and unsafe sex.


•This placed alcohol use ahead of unsafe water
and sanitation, hypertension, high cholesterol,
and tobacco use, and clearly affirms that
alcohol is the most widely abused substance
Loading…
Alcoholism and the Effects of
Alcohol

•In the United States, approximately 100 000
deaths per year are attributed to alcohol abuse.

•Alcohol use is an underlying cause of more
than 30 conditions and a definite contributing
factor to many more, including
–psychotic disorder
–alcoholic cardiomyopathy
–amnesic syndrome
–alcoholic liver disease.
Alcoholism and the Effects of
Alcohol

•The Mayo Clinic defined alcoholism as a
chronic disease in which the body becomes
reliant upon alcohol (ethanol).

•Furthermore, it has been referred to as a
syndrome that consists of 2 phases:
–problem drinking
and
–alcohol addiction.

Alcoholic Liver Disease
•Beverage Alcohol

–Beer 5%

–Wine 12%

–Hard Liquor 40%
(Brandy, wisky, Rum)

–Arrack 40 – 50%
Alcoholism and the Effects of
Alcohol
•A standard alcoholic beverage has been described as any drink that
contains 14 g of pure alcohol.
•Irrespective of what form of alcohol is consumed, the greatest risk
factor appears to be the quantity of alcohol consumed.
•The definition for low-risk drinking for men and women differs,
because
–women suffer from hepatic damage and cirrhosis with considerably smaller
amounts of alcohol consumption.
–A man should not drink more than 4 drinks per day and no more than 14 drinks
per week.
–A woman should not drink more than 3 drinks per day and no more than 7 drinks
per week.
Risk for the development of ALD
Time to develop ALD = to amount of alcohol
consumed

•Men: 60-80 gm/day for 10 years

•Women: 20-40 gm/day for 10 years


Alcoholic cirrhosis, develops ONLY in 10 to 20% of
those who are chronically heavy drinkers.
Loading…
Risk for the development of ALD
•Epidemiology

–Over 90% of chronic heavy drinkers will develop
steatosis

–10 to 20% will develop alcoholic hepatitis

–ALD cause death of 1 in 50 people in Scotland

–4 fold increase in deaths from ALD in past 30
years
Risk for the development of ALD
•Risk of liver disease
–Amount of alcohol consumed
–Genetic factors
–Female sex
–Obesity
–Chronic viral hepatitis
–Nutritional impairment
–drugs
Alcohol Metabolism and the Liver
•The liver is the principal organ for alcohol metabolism.
•The body naturally recognizes ethanol alcohol as a foreign, toxic
agent that can disrupt normal homeostasis.
•When we consume ethanol, it is rapidly absorbed by the upper
gastrointestinal tract.
•Ethanol is
–diffused throughout the body, but exposure is greatest to the liver, via the
main portal vein.
–metabolized by the body in the gastric mucosa and the liver. These organs
manage an enzyme referred to as alcohol dehydrogenase, which is used by
the body to oxidize ethanol and convert it into acetaldehyde and other
metabolites.
–Acetaldehyde ultimately is converted by the body into acetic acid, and then
acetate. Acetaldehyde affects protein synthesis.
Alcohol Metabolism and the Liver


•Alcohol’s metabolites, especially acetaldehyde, damage vital liver
cells because of the excessive generation of free radicals.


•Excessive amount of this type of free radical causes oxidative
stress, which results in the body’s inability to prevent and repair
hepatic damage and the destruction of deoxyribonucleic acid.
Alcohol Metabolism and the Liver
•In addition to the immediate damage of acetaldehyde and the free
radicals, the phagocytic cells of the liver, the Kupffer cells, also
mount an immune response.
•This response is the result of an increase in toxins in the blood that
leak from the intestinal wall and enter the blood stream because of
alcohol consumption.
•The activation of Kupffer cells is responsible for early ethanol-
induced liver injury that ultimately leads to the death of
hepatocytes.
•This damage results in the manifestation of alcoholic liver disease,
and eventually to the development of fibrosis, or scar tissue, within
the liver.

Alcohol Metabolism and the Liver
•Alcohol metabolism differs dramatically between sexes.
–Women are much more likely to suffer from liver damage than men as a
result of alcohol consumption. However, this phenomenon is not clearly
understood.

•In addition to sex, the incidence of liver damage depends on the
– individual’s ethnicity
–genetic predisposition
–nutritional state.
Alcohol and the Liver
•Physical examination :

–vary from normal to evidence of cirrhosis or
hepatic decompensation
•Abdominal wall collaterals (caput medusa),
•Ascites,
•Cutaneous telangiectasias,
•Digital clubbing,
•Dupuytren's contractures,
•Gynecomastia,
•Jaundice,
•Malnutrition ,
•Palmar erythema,
•Peripheral neuropathy,
Alcohol and the Liver
•Laboratory findings:

–serum AST (SGOT), ALT (SGPT), and
gammaglutamyl transferase (GGT) are often
abnormal in alcoholic liver disease

–disproportionate elevation of serum AST (SGOT)
compared to ALT (SGPT) ratio is usually greater
than 2.0

–absolute values of serum AST and ALT are almost
always less than 500 IU/L
Alcohol and the Liver

–Consumption of alcohol can lead to a variety of
histopathologic changes in the liver ranging from
steatosis to cirrhosis
• Steatosis,
•alcoholic hepatitis,
•cirrhosis

–The mechanism behind the development of ALD is not
completely understood, because it is estimated that
only 10% to 20% of alcoholics develop cirrhosis.

Alcoholic Liver Disease
•Signs and symptoms
–Steatosis:
•usually asymptomatic, hepatomegaly

–Alcoholic hepatitis:
•malaise, jaundice, tender hepatomegaly, fever, weight
loss, abdominal discomfort

–Cirrhosis:
•similar to other causes of cirrhosis.
•Hepatomegaly, splenomegaly, malaise, jaundice, weight
loss, ascites, signs of CLD
Alcoholic Liver Disease and
Alcoholic Cirrhosis
•Hepatic steatosis;

–commonly referred to as fatty liver, is a frequent diagnosis that is not
exclusive to patients suffering from ALD.

–Fatty liver is the accumulation of triglycerides in the hepatocytes.

–Fatty liver has been demonstrated in 90% to 100% of all heavy drinkers.

–Short-term exposure to 80 g of alcohol (about 8 beers) over several days can
produce hepatic changes consistent with fatty liver disease.

–Fatty liver may develop after a single large binge and does not predict progression to
hepatitis
Alcohol and the Liver
•ALCOHOLIC FATTY LIVER:
–Fatty liver disease can be reversed if alcohol
consumption is stopped or significantly reduced.
–progression to fibrosis or cirrhosis occurred only in
patients who continued to ingest alcohol

–there are often no clinical symptoms, so fatty
liver may be undiagnosed. The only
complaint may be mild tender
hepatomegaly.

Alcohol and the Liver
•ALCOHOLIC FATTY LIVER:
•Pathology:
– macrovesicular fatty infiltration
–inflammatory changes are minimal
–fatty liver is not pathognomonic of ethanol ingestion:
• starvation,
•fatty liver of pregnancy,
•drug toxicity (valproic acid, tetracycline,
•antiviral agents such as zidovudine and dideoxyinosine),
•nonalcoholic steatohepatitis,
•viral hepatitis, particularly hepatitis C virus,
•Reye's syndrome,
•inborn errors of metabolism (such as defects in mitochondrial beta
oxidation)
Alcoholic Liver Disease and
Alcoholic Cirrhosis
•Alcoholic hepatitis
–fatty liver with the development of hepatitis, referred to as steatohepatitis, has
been acknowledged as a precursor for the development of cirrhosis.

–Alcoholic hepatitis results directly from alcohol abuse and is observed in as
many as 35% of heavy drinkers.

–Like other forms of hepatitis, alcoholic hepatitis can be subclinical.

–Laboratory findings are more predictive if the disease has progressed.

–Approximately 40% of patients with alcoholic hepatitis who continue to
drink will develop alcoholic cirrhosis within 1 to 2 years.
Alcohol and the Liver

•ALCOHOLIC HEPATITIS:

3. Alcohol and the Liver

Alcohol and the Liver
• There is a broad spectrum of clinical and
laboratory findings in patients with alcoholic
liver disease, ranging from asymptomatic
fatty liver to alcoholic hepatitis to end-stage
liver failure with jaundice, coagulopathy, and
encephalopathy
Loading…
Alcohol and the Liver
• FINDINGS IN ALCOHOLIC LIVER
DISEASE

–moderate alcohol intake appears to have
cardiovascular benefits

– excessive alcohol intake can be associated with
significant social and physical consequences

–for the development of cirrhosis:
•requirement for 80 grams of ethanol daily for 10 to 20
Alcohol and the liver

•In 2009, WHO listed alcohol use as one of the
leading causes of the global burden of
disease and injury, surpassed only slightly by
childhood malnourishment and unsafe sex.


•This placed alcohol use ahead of unsafe water
and sanitation, hypertension, high cholesterol,
and tobacco use, and clearly affirms that
alcohol is the most widely abused substance
Loading…
Alcoholism and the Effects of
Alcohol

•In the United States, approximately 100 000
deaths per year are attributed to alcohol abuse.

•Alcohol use is an underlying cause of more
than 30 conditions and a definite contributing
factor to many more, including
–psychotic disorder
–alcoholic cardiomyopathy
–amnesic syndrome
–alcoholic liver disease.
Alcoholism and the Effects of
Alcohol

•The Mayo Clinic defined alcoholism as a
chronic disease in which the body becomes
reliant upon alcohol (ethanol).

•Furthermore, it has been referred to as a
syndrome that consists of 2 phases:
–problem drinking
and
–alcohol addiction.

Alcoholic Liver Disease
•Beverage Alcohol

–Beer 5%

–Wine 12%

–Hard Liquor 40%
(Brandy, wisky, Rum)

–Arrack 40 – 50%
Alcoholism and the Effects of
Alcohol
•A standard alcoholic beverage has been described as any drink that
contains 14 g of pure alcohol.
•Irrespective of what form of alcohol is consumed, the greatest risk
factor appears to be the quantity of alcohol consumed.
•The definition for low-risk drinking for men and women differs,
because
–women suffer from hepatic damage and cirrhosis with considerably smaller
amounts of alcohol consumption.
–A man should not drink more than 4 drinks per day and no more than 14 drinks
per week.
–A woman should not drink more than 3 drinks per day and no more than 7 drinks
per week.
Risk for the development of ALD
Time to develop ALD = to amount of alcohol
consumed

•Men: 60-80 gm/day for 10 years

•Women: 20-40 gm/day for 10 years


Alcoholic cirrhosis, develops ONLY in 10 to 20% of
those who are chronically heavy drinkers.
Loading…
Risk for the development of ALD
•Epidemiology

–Over 90% of chronic heavy drinkers will develop
steatosis

–10 to 20% will develop alcoholic hepatitis

–ALD cause death of 1 in 50 people in Scotland

–4 fold increase in deaths from ALD in past 30
years
Risk for the development of ALD
•Risk of liver disease
–Amount of alcohol consumed
–Genetic factors
–Female sex
–Obesity
–Chronic viral hepatitis
–Nutritional impairment
–drugs
Alcohol Metabolism and the Liver
•The liver is the principal organ for alcohol metabolism.
•The body naturally recognizes ethanol alcohol as a foreign, toxic
agent that can disrupt normal homeostasis.
•When we consume ethanol, it is rapidly absorbed by the upper
gastrointestinal tract.
•Ethanol is
–diffused throughout the body, but exposure is greatest to the liver, via the
main portal vein.
–metabolized by the body in the gastric mucosa and the liver. These organs
manage an enzyme referred to as alcohol dehydrogenase, which is used by
the body to oxidize ethanol and convert it into acetaldehyde and other
metabolites.
–Acetaldehyde ultimately is converted by the body into acetic acid, and then
acetate. Acetaldehyde affects protein synthesis.
Alcohol Metabolism and the Liver


•Alcohol’s metabolites, especially acetaldehyde, damage vital liver
cells because of the excessive generation of free radicals.


•Excessive amount of this type of free radical causes oxidative
stress, which results in the body’s inability to prevent and repair
hepatic damage and the destruction of deoxyribonucleic acid.
Alcohol Metabolism and the Liver
•In addition to the immediate damage of acetaldehyde and the free
radicals, the phagocytic cells of the liver, the Kupffer cells, also
mount an immune response.
•This response is the result of an increase in toxins in the blood that
leak from the intestinal wall and enter the blood stream because of
alcohol consumption.
•The activation of Kupffer cells is responsible for early ethanol-
induced liver injury that ultimately leads to the death of
hepatocytes.
•This damage results in the manifestation of alcoholic liver disease,
and eventually to the development of fibrosis, or scar tissue, within
the liver.

Alcohol Metabolism and the Liver
•Alcohol metabolism differs dramatically between sexes.
–Women are much more likely to suffer from liver damage than men as a
result of alcohol consumption. However, this phenomenon is not clearly
understood.

•In addition to sex, the incidence of liver damage depends on the
– individual’s ethnicity
–genetic predisposition
–nutritional state.
Alcohol and the Liver
•Physical examination :

–vary from normal to evidence of cirrhosis or
hepatic decompensation
•Abdominal wall collaterals (caput medusa),
•Ascites,
•Cutaneous telangiectasias,
•Digital clubbing,
•Dupuytren's contractures,
•Gynecomastia,
•Jaundice,
•Malnutrition ,
•Palmar erythema,
•Peripheral neuropathy,
Alcohol and the Liver
•Laboratory findings:

–serum AST (SGOT), ALT (SGPT), and
gammaglutamyl transferase (GGT) are often
abnormal in alcoholic liver disease

–disproportionate elevation of serum AST (SGOT)
compared to ALT (SGPT) ratio is usually greater
than 2.0

–absolute values of serum AST and ALT are almost
always less than 500 IU/L
Alcohol and the Liver

–Consumption of alcohol can lead to a variety of
histopathologic changes in the liver ranging from
steatosis to cirrhosis
• Steatosis,
•alcoholic hepatitis,
•cirrhosis

–The mechanism behind the development of ALD is not
completely understood, because it is estimated that
only 10% to 20% of alcoholics develop cirrhosis.

Alcoholic Liver Disease
•Signs and symptoms
–Steatosis:
•usually asymptomatic, hepatomegaly

–Alcoholic hepatitis:
•malaise, jaundice, tender hepatomegaly, fever, weight
loss, abdominal discomfort

–Cirrhosis:
•similar to other causes of cirrhosis.
•Hepatomegaly, splenomegaly, malaise, jaundice, weight
loss, ascites, signs of CLD
Alcoholic Liver Disease and
Alcoholic Cirrhosis
•Hepatic steatosis;

–commonly referred to as fatty liver, is a frequent diagnosis that is not
exclusive to patients suffering from ALD.

–Fatty liver is the accumulation of triglycerides in the hepatocytes.

–Fatty liver has been demonstrated in 90% to 100% of all heavy drinkers.

–Short-term exposure to 80 g of alcohol (about 8 beers) over several days can
produce hepatic changes consistent with fatty liver disease.

–Fatty liver may develop after a single large binge and does not predict progression to
hepatitis
Alcohol and the Liver
•ALCOHOLIC FATTY LIVER:
–Fatty liver disease can be reversed if alcohol
consumption is stopped or significantly reduced.
–progression to fibrosis or cirrhosis occurred only in
patients who continued to ingest alcohol

–there are often no clinical symptoms, so fatty
liver may be undiagnosed. The only
complaint may be mild tender
hepatomegaly.

Alcohol and the Liver
•ALCOHOLIC FATTY LIVER:
•Pathology:
– macrovesicular fatty infiltration
–inflammatory changes are minimal
–fatty liver is not pathognomonic of ethanol ingestion:
• starvation,
•fatty liver of pregnancy,
•drug toxicity (valproic acid, tetracycline,
•antiviral agents such as zidovudine and dideoxyinosine),
•nonalcoholic steatohepatitis,
•viral hepatitis, particularly hepatitis C virus,
•Reye's syndrome,
•inborn errors of metabolism (such as defects in mitochondrial beta
oxidation)
Alcoholic Liver Disease and
Alcoholic Cirrhosis
•Alcoholic hepatitis
–fatty liver with the development of hepatitis, referred to as steatohepatitis, has
been acknowledged as a precursor for the development of cirrhosis.

–Alcoholic hepatitis results directly from alcohol abuse and is observed in as
many as 35% of heavy drinkers.

–Like other forms of hepatitis, alcoholic hepatitis can be subclinical.

–Laboratory findings are more predictive if the disease has progressed.

–Approximately 40% of patients with alcoholic hepatitis who continue to
drink will develop alcoholic cirrhosis within 1 to 2 years.
Alcohol and the Liver

•ALCOHOLIC HEPATITIS:

4. Alcohol and the Liver

Alcohol and the Liver
• There is a broad spectrum of clinical and
laboratory findings in patients with alcoholic
liver disease, ranging from asymptomatic
fatty liver to alcoholic hepatitis to end-stage
liver failure with jaundice, coagulopathy, and
encephalopathy
Loading…
Alcohol and the Liver
• FINDINGS IN ALCOHOLIC LIVER
DISEASE

–moderate alcohol intake appears to have
cardiovascular benefits

– excessive alcohol intake can be associated with
significant social and physical consequences

–for the development of cirrhosis:
•requirement for 80 grams of ethanol daily for 10 to 20
Alcohol and the liver

•In 2009, WHO listed alcohol use as one of the
leading causes of the global burden of
disease and injury, surpassed only slightly by
childhood malnourishment and unsafe sex.


•This placed alcohol use ahead of unsafe water
and sanitation, hypertension, high cholesterol,
and tobacco use, and clearly affirms that
alcohol is the most widely abused substance
Loading…
Alcoholism and the Effects of
Alcohol

•In the United States, approximately 100 000
deaths per year are attributed to alcohol abuse.

•Alcohol use is an underlying cause of more
than 30 conditions and a definite contributing
factor to many more, including
–psychotic disorder
–alcoholic cardiomyopathy
–amnesic syndrome
–alcoholic liver disease.
Alcoholism and the Effects of
Alcohol

•The Mayo Clinic defined alcoholism as a
chronic disease in which the body becomes
reliant upon alcohol (ethanol).

•Furthermore, it has been referred to as a
syndrome that consists of 2 phases:
–problem drinking
and
–alcohol addiction.

Alcoholic Liver Disease
•Beverage Alcohol

–Beer 5%

–Wine 12%

–Hard Liquor 40%
(Brandy, wisky, Rum)

–Arrack 40 – 50%
Alcoholism and the Effects of
Alcohol
•A standard alcoholic beverage has been described as any drink that
contains 14 g of pure alcohol.
•Irrespective of what form of alcohol is consumed, the greatest risk
factor appears to be the quantity of alcohol consumed.
•The definition for low-risk drinking for men and women differs,
because
–women suffer from hepatic damage and cirrhosis with considerably smaller
amounts of alcohol consumption.
–A man should not drink more than 4 drinks per day and no more than 14 drinks
per week.
–A woman should not drink more than 3 drinks per day and no more than 7 drinks
per week.
Risk for the development of ALD
Time to develop ALD = to amount of alcohol
consumed

•Men: 60-80 gm/day for 10 years

•Women: 20-40 gm/day for 10 years


Alcoholic cirrhosis, develops ONLY in 10 to 20% of
those who are chronically heavy drinkers.
Loading…
Risk for the development of ALD
•Epidemiology

–Over 90% of chronic heavy drinkers will develop
steatosis

–10 to 20% will develop alcoholic hepatitis

–ALD cause death of 1 in 50 people in Scotland

–4 fold increase in deaths from ALD in past 30
years
Risk for the development of ALD
•Risk of liver disease
–Amount of alcohol consumed
–Genetic factors
–Female sex
–Obesity
–Chronic viral hepatitis
–Nutritional impairment
–drugs
Alcohol Metabolism and the Liver
•The liver is the principal organ for alcohol metabolism.
•The body naturally recognizes ethanol alcohol as a foreign, toxic
agent that can disrupt normal homeostasis.
•When we consume ethanol, it is rapidly absorbed by the upper
gastrointestinal tract.
•Ethanol is
–diffused throughout the body, but exposure is greatest to the liver, via the
main portal vein.
–metabolized by the body in the gastric mucosa and the liver. These organs
manage an enzyme referred to as alcohol dehydrogenase, which is used by
the body to oxidize ethanol and convert it into acetaldehyde and other
metabolites.
–Acetaldehyde ultimately is converted by the body into acetic acid, and then
acetate. Acetaldehyde affects protein synthesis.
Alcohol Metabolism and the Liver


•Alcohol’s metabolites, especially acetaldehyde, damage vital liver
cells because of the excessive generation of free radicals.


•Excessive amount of this type of free radical causes oxidative
stress, which results in the body’s inability to prevent and repair
hepatic damage and the destruction of deoxyribonucleic acid.
Alcohol Metabolism and the Liver
•In addition to the immediate damage of acetaldehyde and the free
radicals, the phagocytic cells of the liver, the Kupffer cells, also
mount an immune response.
•This response is the result of an increase in toxins in the blood that
leak from the intestinal wall and enter the blood stream because of
alcohol consumption.
•The activation of Kupffer cells is responsible for early ethanol-
induced liver injury that ultimately leads to the death of
hepatocytes.
•This damage results in the manifestation of alcoholic liver disease,
and eventually to the development of fibrosis, or scar tissue, within
the liver.

Alcohol Metabolism and the Liver
•Alcohol metabolism differs dramatically between sexes.
–Women are much more likely to suffer from liver damage than men as a
result of alcohol consumption. However, this phenomenon is not clearly
understood.

•In addition to sex, the incidence of liver damage depends on the
– individual’s ethnicity
–genetic predisposition
–nutritional state.
Alcohol and the Liver
•Physical examination :

–vary from normal to evidence of cirrhosis or
hepatic decompensation
•Abdominal wall collaterals (caput medusa),
•Ascites,
•Cutaneous telangiectasias,
•Digital clubbing,
•Dupuytren's contractures,
•Gynecomastia,
•Jaundice,
•Malnutrition ,
•Palmar erythema,
•Peripheral neuropathy,
Alcohol and the Liver
•Laboratory findings:

–serum AST (SGOT), ALT (SGPT), and
gammaglutamyl transferase (GGT) are often
abnormal in alcoholic liver disease

–disproportionate elevation of serum AST (SGOT)
compared to ALT (SGPT) ratio is usually greater
than 2.0

–absolute values of serum AST and ALT are almost
always less than 500 IU/L
Alcohol and the Liver

–Consumption of alcohol can lead to a variety of
histopathologic changes in the liver ranging from
steatosis to cirrhosis
• Steatosis,
•alcoholic hepatitis,
•cirrhosis

–The mechanism behind the development of ALD is not
completely understood, because it is estimated that
only 10% to 20% of alcoholics develop cirrhosis.

Alcoholic Liver Disease
•Signs and symptoms
–Steatosis:
•usually asymptomatic, hepatomegaly

–Alcoholic hepatitis:
•malaise, jaundice, tender hepatomegaly, fever, weight
loss, abdominal discomfort

–Cirrhosis:
•similar to other causes of cirrhosis.
•Hepatomegaly, splenomegaly, malaise, jaundice, weight
loss, ascites, signs of CLD
Alcoholic Liver Disease and
Alcoholic Cirrhosis
•Hepatic steatosis;

–commonly referred to as fatty liver, is a frequent diagnosis that is not
exclusive to patients suffering from ALD.

–Fatty liver is the accumulation of triglycerides in the hepatocytes.

–Fatty liver has been demonstrated in 90% to 100% of all heavy drinkers.

–Short-term exposure to 80 g of alcohol (about 8 beers) over several days can
produce hepatic changes consistent with fatty liver disease.

–Fatty liver may develop after a single large binge and does not predict progression to
hepatitis
Alcohol and the Liver
•ALCOHOLIC FATTY LIVER:
–Fatty liver disease can be reversed if alcohol
consumption is stopped or significantly reduced.
–progression to fibrosis or cirrhosis occurred only in
patients who continued to ingest alcohol

–there are often no clinical symptoms, so fatty
liver may be undiagnosed. The only
complaint may be mild tender
hepatomegaly.

Alcohol and the Liver
•ALCOHOLIC FATTY LIVER:
•Pathology:
– macrovesicular fatty infiltration
–inflammatory changes are minimal
–fatty liver is not pathognomonic of ethanol ingestion:
• starvation,
•fatty liver of pregnancy,
•drug toxicity (valproic acid, tetracycline,
•antiviral agents such as zidovudine and dideoxyinosine),
•nonalcoholic steatohepatitis,
•viral hepatitis, particularly hepatitis C virus,
•Reye's syndrome,
•inborn errors of metabolism (such as defects in mitochondrial beta
oxidation)
Alcoholic Liver Disease and
Alcoholic Cirrhosis
•Alcoholic hepatitis
–fatty liver with the development of hepatitis, referred to as steatohepatitis, has
been acknowledged as a precursor for the development of cirrhosis.

–Alcoholic hepatitis results directly from alcohol abuse and is observed in as
many as 35% of heavy drinkers.

–Like other forms of hepatitis, alcoholic hepatitis can be subclinical.

–Laboratory findings are more predictive if the disease has progressed.

–Approximately 40% of patients with alcoholic hepatitis who continue to
drink will develop alcoholic cirrhosis within 1 to 2 years.
Alcohol and the Liver

•ALCOHOLIC HEPATITIS:

5. Alcohol and the Liver

Alcohol and the Liver
• There is a broad spectrum of clinical and
laboratory findings in patients with alcoholic
liver disease, ranging from asymptomatic
fatty liver to alcoholic hepatitis to end-stage
liver failure with jaundice, coagulopathy, and
encephalopathy
Loading…
Alcohol and the Liver
• FINDINGS IN ALCOHOLIC LIVER
DISEASE

–moderate alcohol intake appears to have
cardiovascular benefits

– excessive alcohol intake can be associated with
significant social and physical consequences

–for the development of cirrhosis:
•requirement for 80 grams of ethanol daily for 10 to 20
Alcohol and the liver

•In 2009, WHO listed alcohol use as one of the
leading causes of the global burden of
disease and injury, surpassed only slightly by
childhood malnourishment and unsafe sex.


•This placed alcohol use ahead of unsafe water
and sanitation, hypertension, high cholesterol,
and tobacco use, and clearly affirms that
alcohol is the most widely abused substance
Loading…
Alcoholism and the Effects of
Alcohol

•In the United States, approximately 100 000
deaths per year are attributed to alcohol abuse.

•Alcohol use is an underlying cause of more
than 30 conditions and a definite contributing
factor to many more, including
–psychotic disorder
–alcoholic cardiomyopathy
–amnesic syndrome
–alcoholic liver disease.
Alcoholism and the Effects of
Alcohol

•The Mayo Clinic defined alcoholism as a
chronic disease in which the body becomes
reliant upon alcohol (ethanol).

•Furthermore, it has been referred to as a
syndrome that consists of 2 phases:
–problem drinking
and
–alcohol addiction.

Alcoholic Liver Disease
•Beverage Alcohol

–Beer 5%

–Wine 12%

–Hard Liquor 40%
(Brandy, wisky, Rum)

–Arrack 40 – 50%
Alcoholism and the Effects of
Alcohol
•A standard alcoholic beverage has been described as any drink that
contains 14 g of pure alcohol.
•Irrespective of what form of alcohol is consumed, the greatest risk
factor appears to be the quantity of alcohol consumed.
•The definition for low-risk drinking for men and women differs,
because
–women suffer from hepatic damage and cirrhosis with considerably smaller
amounts of alcohol consumption.
–A man should not drink more than 4 drinks per day and no more than 14 drinks
per week.
–A woman should not drink more than 3 drinks per day and no more than 7 drinks
per week.
Risk for the development of ALD
Time to develop ALD = to amount of alcohol
consumed

•Men: 60-80 gm/day for 10 years

•Women: 20-40 gm/day for 10 years


Alcoholic cirrhosis, develops ONLY in 10 to 20% of
those who are chronically heavy drinkers.
Loading…
Risk for the development of ALD
•Epidemiology

–Over 90% of chronic heavy drinkers will develop
steatosis

–10 to 20% will develop alcoholic hepatitis

–ALD cause death of 1 in 50 people in Scotland

–4 fold increase in deaths from ALD in past 30
years
Risk for the development of ALD
•Risk of liver disease
–Amount of alcohol consumed
–Genetic factors
–Female sex
–Obesity
–Chronic viral hepatitis
–Nutritional impairment
–drugs
Alcohol Metabolism and the Liver
•The liver is the principal organ for alcohol metabolism.
•The body naturally recognizes ethanol alcohol as a foreign, toxic
agent that can disrupt normal homeostasis.
•When we consume ethanol, it is rapidly absorbed by the upper
gastrointestinal tract.
•Ethanol is
–diffused throughout the body, but exposure is greatest to the liver, via the
main portal vein.
–metabolized by the body in the gastric mucosa and the liver. These organs
manage an enzyme referred to as alcohol dehydrogenase, which is used by
the body to oxidize ethanol and convert it into acetaldehyde and other
metabolites.
–Acetaldehyde ultimately is converted by the body into acetic acid, and then
acetate. Acetaldehyde affects protein synthesis.
Alcohol Metabolism and the Liver


•Alcohol’s metabolites, especially acetaldehyde, damage vital liver
cells because of the excessive generation of free radicals.


•Excessive amount of this type of free radical causes oxidative
stress, which results in the body’s inability to prevent and repair
hepatic damage and the destruction of deoxyribonucleic acid.
Alcohol Metabolism and the Liver
•In addition to the immediate damage of acetaldehyde and the free
radicals, the phagocytic cells of the liver, the Kupffer cells, also
mount an immune response.
•This response is the result of an increase in toxins in the blood that
leak from the intestinal wall and enter the blood stream because of
alcohol consumption.
•The activation of Kupffer cells is responsible for early ethanol-
induced liver injury that ultimately leads to the death of
hepatocytes.
•This damage results in the manifestation of alcoholic liver disease,
and eventually to the development of fibrosis, or scar tissue, within
the liver.

Alcohol Metabolism and the Liver
•Alcohol metabolism differs dramatically between sexes.
–Women are much more likely to suffer from liver damage than men as a
result of alcohol consumption. However, this phenomenon is not clearly
understood.

•In addition to sex, the incidence of liver damage depends on the
– individual’s ethnicity
–genetic predisposition
–nutritional state.
Alcohol and the Liver
•Physical examination :

–vary from normal to evidence of cirrhosis or
hepatic decompensation
•Abdominal wall collaterals (caput medusa),
•Ascites,
•Cutaneous telangiectasias,
•Digital clubbing,
•Dupuytren's contractures,
•Gynecomastia,
•Jaundice,
•Malnutrition ,
•Palmar erythema,
•Peripheral neuropathy,
Alcohol and the Liver
•Laboratory findings:

–serum AST (SGOT), ALT (SGPT), and
gammaglutamyl transferase (GGT) are often
abnormal in alcoholic liver disease

–disproportionate elevation of serum AST (SGOT)
compared to ALT (SGPT) ratio is usually greater
than 2.0

–absolute values of serum AST and ALT are almost
always less than 500 IU/L
Alcohol and the Liver

–Consumption of alcohol can lead to a variety of
histopathologic changes in the liver ranging from
steatosis to cirrhosis
• Steatosis,
•alcoholic hepatitis,
•cirrhosis

–The mechanism behind the development of ALD is not
completely understood, because it is estimated that
only 10% to 20% of alcoholics develop cirrhosis.

Alcoholic Liver Disease
•Signs and symptoms
–Steatosis:
•usually asymptomatic, hepatomegaly

–Alcoholic hepatitis:
•malaise, jaundice, tender hepatomegaly, fever, weight
loss, abdominal discomfort

–Cirrhosis:
•similar to other causes of cirrhosis.
•Hepatomegaly, splenomegaly, malaise, jaundice, weight
loss, ascites, signs of CLD
Alcoholic Liver Disease and
Alcoholic Cirrhosis
•Hepatic steatosis;

–commonly referred to as fatty liver, is a frequent diagnosis that is not
exclusive to patients suffering from ALD.

–Fatty liver is the accumulation of triglycerides in the hepatocytes.

–Fatty liver has been demonstrated in 90% to 100% of all heavy drinkers.

–Short-term exposure to 80 g of alcohol (about 8 beers) over several days can
produce hepatic changes consistent with fatty liver disease.

–Fatty liver may develop after a single large binge and does not predict progression to
hepatitis
Alcohol and the Liver
•ALCOHOLIC FATTY LIVER:
–Fatty liver disease can be reversed if alcohol
consumption is stopped or significantly reduced.
–progression to fibrosis or cirrhosis occurred only in
patients who continued to ingest alcohol

–there are often no clinical symptoms, so fatty
liver may be undiagnosed. The only
complaint may be mild tender
hepatomegaly.

Alcohol and the Liver
•ALCOHOLIC FATTY LIVER:
•Pathology:
– macrovesicular fatty infiltration
–inflammatory changes are minimal
–fatty liver is not pathognomonic of ethanol ingestion:
• starvation,
•fatty liver of pregnancy,
•drug toxicity (valproic acid, tetracycline,
•antiviral agents such as zidovudine and dideoxyinosine),
•nonalcoholic steatohepatitis,
•viral hepatitis, particularly hepatitis C virus,
•Reye's syndrome,
•inborn errors of metabolism (such as defects in mitochondrial beta
oxidation)
Alcoholic Liver Disease and
Alcoholic Cirrhosis
•Alcoholic hepatitis
–fatty liver with the development of hepatitis, referred to as steatohepatitis, has
been acknowledged as a precursor for the development of cirrhosis.

–Alcoholic hepatitis results directly from alcohol abuse and is observed in as
many as 35% of heavy drinkers.

–Like other forms of hepatitis, alcoholic hepatitis can be subclinical.

–Laboratory findings are more predictive if the disease has progressed.

–Approximately 40% of patients with alcoholic hepatitis who continue to
drink will develop alcoholic cirrhosis within 1 to 2 years.
Alcohol and the Liver

•ALCOHOLIC HEPATITIS:

6. Alcohol and the Liver

Alcohol and the Liver
• There is a broad spectrum of clinical and
laboratory findings in patients with alcoholic
liver disease, ranging from asymptomatic
fatty liver to alcoholic hepatitis to end-stage
liver failure with jaundice, coagulopathy, and
encephalopathy
Loading…
Alcohol and the Liver
• FINDINGS IN ALCOHOLIC LIVER
DISEASE

–moderate alcohol intake appears to have
cardiovascular benefits

– excessive alcohol intake can be associated with
significant social and physical consequences

–for the development of cirrhosis:
•requirement for 80 grams of ethanol daily for 10 to 20
Alcohol and the liver

•In 2009, WHO listed alcohol use as one of the
leading causes of the global burden of
disease and injury, surpassed only slightly by
childhood malnourishment and unsafe sex.


•This placed alcohol use ahead of unsafe water
and sanitation, hypertension, high cholesterol,
and tobacco use, and clearly affirms that
alcohol is the most widely abused substance
Loading…
Alcoholism and the Effects of
Alcohol

•In the United States, approximately 100 000
deaths per year are attributed to alcohol abuse.

•Alcohol use is an underlying cause of more
than 30 conditions and a definite contributing
factor to many more, including
–psychotic disorder
–alcoholic cardiomyopathy
–amnesic syndrome
–alcoholic liver disease.
Alcoholism and the Effects of
Alcohol

•The Mayo Clinic defined alcoholism as a
chronic disease in which the body becomes
reliant upon alcohol (ethanol).

•Furthermore, it has been referred to as a
syndrome that consists of 2 phases:
–problem drinking
and
–alcohol addiction.

Alcoholic Liver Disease
•Beverage Alcohol

–Beer 5%

–Wine 12%

–Hard Liquor 40%
(Brandy, wisky, Rum)

–Arrack 40 – 50%
Alcoholism and the Effects of
Alcohol
•A standard alcoholic beverage has been described as any drink that
contains 14 g of pure alcohol.
•Irrespective of what form of alcohol is consumed, the greatest risk
factor appears to be the quantity of alcohol consumed.
•The definition for low-risk drinking for men and women differs,
because
–women suffer from hepatic damage and cirrhosis with considerably smaller
amounts of alcohol consumption.
–A man should not drink more than 4 drinks per day and no more than 14 drinks
per week.
–A woman should not drink more than 3 drinks per day and no more than 7 drinks
per week.
Risk for the development of ALD
Time to develop ALD = to amount of alcohol
consumed

•Men: 60-80 gm/day for 10 years

•Women: 20-40 gm/day for 10 years


Alcoholic cirrhosis, develops ONLY in 10 to 20% of
those who are chronically heavy drinkers.
Loading…
Risk for the development of ALD
•Epidemiology

–Over 90% of chronic heavy drinkers will develop
steatosis

–10 to 20% will develop alcoholic hepatitis

–ALD cause death of 1 in 50 people in Scotland

–4 fold increase in deaths from ALD in past 30
years
Risk for the development of ALD
•Risk of liver disease
–Amount of alcohol consumed
–Genetic factors
–Female sex
–Obesity
–Chronic viral hepatitis
–Nutritional impairment
–drugs
Alcohol Metabolism and the Liver
•The liver is the principal organ for alcohol metabolism.
•The body naturally recognizes ethanol alcohol as a foreign, toxic
agent that can disrupt normal homeostasis.
•When we consume ethanol, it is rapidly absorbed by the upper
gastrointestinal tract.
•Ethanol is
–diffused throughout the body, but exposure is greatest to the liver, via the
main portal vein.
–metabolized by the body in the gastric mucosa and the liver. These organs
manage an enzyme referred to as alcohol dehydrogenase, which is used by
the body to oxidize ethanol and convert it into acetaldehyde and other
metabolites.
–Acetaldehyde ultimately is converted by the body into acetic acid, and then
acetate. Acetaldehyde affects protein synthesis.
Alcohol Metabolism and the Liver


•Alcohol’s metabolites, especially acetaldehyde, damage vital liver
cells because of the excessive generation of free radicals.


•Excessive amount of this type of free radical causes oxidative
stress, which results in the body’s inability to prevent and repair
hepatic damage and the destruction of deoxyribonucleic acid.
Alcohol Metabolism and the Liver
•In addition to the immediate damage of acetaldehyde and the free
radicals, the phagocytic cells of the liver, the Kupffer cells, also
mount an immune response.
•This response is the result of an increase in toxins in the blood that
leak from the intestinal wall and enter the blood stream because of
alcohol consumption.
•The activation of Kupffer cells is responsible for early ethanol-
induced liver injury that ultimately leads to the death of
hepatocytes.
•This damage results in the manifestation of alcoholic liver disease,
and eventually to the development of fibrosis, or scar tissue, within
the liver.

Alcohol Metabolism and the Liver
•Alcohol metabolism differs dramatically between sexes.
–Women are much more likely to suffer from liver damage than men as a
result of alcohol consumption. However, this phenomenon is not clearly
understood.

•In addition to sex, the incidence of liver damage depends on the
– individual’s ethnicity
–genetic predisposition
–nutritional state.
Alcohol and the Liver
•Physical examination :

–vary from normal to evidence of cirrhosis or
hepatic decompensation
•Abdominal wall collaterals (caput medusa),
•Ascites,
•Cutaneous telangiectasias,
•Digital clubbing,
•Dupuytren's contractures,
•Gynecomastia,
•Jaundice,
•Malnutrition ,
•Palmar erythema,
•Peripheral neuropathy,
Alcohol and the Liver
•Laboratory findings:

–serum AST (SGOT), ALT (SGPT), and
gammaglutamyl transferase (GGT) are often
abnormal in alcoholic liver disease

–disproportionate elevation of serum AST (SGOT)
compared to ALT (SGPT) ratio is usually greater
than 2.0

–absolute values of serum AST and ALT are almost
always less than 500 IU/L
Alcohol and the Liver

–Consumption of alcohol can lead to a variety of
histopathologic changes in the liver ranging from
steatosis to cirrhosis
• Steatosis,
•alcoholic hepatitis,
•cirrhosis

–The mechanism behind the development of ALD is not
completely understood, because it is estimated that
only 10% to 20% of alcoholics develop cirrhosis.

Alcoholic Liver Disease
•Signs and symptoms
–Steatosis:
•usually asymptomatic, hepatomegaly

–Alcoholic hepatitis:
•malaise, jaundice, tender hepatomegaly, fever, weight
loss, abdominal discomfort

–Cirrhosis:
•similar to other causes of cirrhosis.
•Hepatomegaly, splenomegaly, malaise, jaundice, weight
loss, ascites, signs of CLD
Alcoholic Liver Disease and
Alcoholic Cirrhosis
•Hepatic steatosis;

–commonly referred to as fatty liver, is a frequent diagnosis that is not
exclusive to patients suffering from ALD.

–Fatty liver is the accumulation of triglycerides in the hepatocytes.

–Fatty liver has been demonstrated in 90% to 100% of all heavy drinkers.

–Short-term exposure to 80 g of alcohol (about 8 beers) over several days can
produce hepatic changes consistent with fatty liver disease.

–Fatty liver may develop after a single large binge and does not predict progression to
hepatitis
Alcohol and the Liver
•ALCOHOLIC FATTY LIVER:
–Fatty liver disease can be reversed if alcohol
consumption is stopped or significantly reduced.
–progression to fibrosis or cirrhosis occurred only in
patients who continued to ingest alcohol

–there are often no clinical symptoms, so fatty
liver may be undiagnosed. The only
complaint may be mild tender
hepatomegaly.

Alcohol and the Liver
•ALCOHOLIC FATTY LIVER:
•Pathology:
– macrovesicular fatty infiltration
–inflammatory changes are minimal
–fatty liver is not pathognomonic of ethanol ingestion:
• starvation,
•fatty liver of pregnancy,
•drug toxicity (valproic acid, tetracycline,
•antiviral agents such as zidovudine and dideoxyinosine),
•nonalcoholic steatohepatitis,
•viral hepatitis, particularly hepatitis C virus,
•Reye's syndrome,
•inborn errors of metabolism (such as defects in mitochondrial beta
oxidation)
Alcoholic Liver Disease and
Alcoholic Cirrhosis
•Alcoholic hepatitis
–fatty liver with the development of hepatitis, referred to as steatohepatitis, has
been acknowledged as a precursor for the development of cirrhosis.

–Alcoholic hepatitis results directly from alcohol abuse and is observed in as
many as 35% of heavy drinkers.

–Like other forms of hepatitis, alcoholic hepatitis can be subclinical.

–Laboratory findings are more predictive if the disease has progressed.

–Approximately 40% of patients with alcoholic hepatitis who continue to
drink will develop alcoholic cirrhosis within 1 to 2 years.
Alcohol and the Liver

•ALCOHOLIC HEPATITIS:

7. Alcohol and the Liver

Alcohol and the Liver
• There is a broad spectrum of clinical and
laboratory findings in patients with alcoholic
liver disease, ranging from asymptomatic
fatty liver to alcoholic hepatitis to end-stage
liver failure with jaundice, coagulopathy, and
encephalopathy
Loading…
Alcohol and the Liver
• FINDINGS IN ALCOHOLIC LIVER
DISEASE

–moderate alcohol intake appears to have
cardiovascular benefits

– excessive alcohol intake can be associated with
significant social and physical consequences

–for the development of cirrhosis:
•requirement for 80 grams of ethanol daily for 10 to 20
Alcohol and the liver

•In 2009, WHO listed alcohol use as one of the
leading causes of the global burden of
disease and injury, surpassed only slightly by
childhood malnourishment and unsafe sex.


•This placed alcohol use ahead of unsafe water
and sanitation, hypertension, high cholesterol,
and tobacco use, and clearly affirms that
alcohol is the most widely abused substance
Loading…
Alcoholism and the Effects of
Alcohol

•In the United States, approximately 100 000
deaths per year are attributed to alcohol abuse.

•Alcohol use is an underlying cause of more
than 30 conditions and a definite contributing
factor to many more, including
–psychotic disorder
–alcoholic cardiomyopathy
–amnesic syndrome
–alcoholic liver disease.
Alcoholism and the Effects of
Alcohol

•The Mayo Clinic defined alcoholism as a
chronic disease in which the body becomes
reliant upon alcohol (ethanol).

•Furthermore, it has been referred to as a
syndrome that consists of 2 phases:
–problem drinking
and
–alcohol addiction.

Alcoholic Liver Disease
•Beverage Alcohol

–Beer 5%

–Wine 12%

–Hard Liquor 40%
(Brandy, wisky, Rum)

–Arrack 40 – 50%
Alcoholism and the Effects of
Alcohol
•A standard alcoholic beverage has been described as any drink that
contains 14 g of pure alcohol.
•Irrespective of what form of alcohol is consumed, the greatest risk
factor appears to be the quantity of alcohol consumed.
•The definition for low-risk drinking for men and women differs,
because
–women suffer from hepatic damage and cirrhosis with considerably smaller
amounts of alcohol consumption.
–A man should not drink more than 4 drinks per day and no more than 14 drinks
per week.
–A woman should not drink more than 3 drinks per day and no more than 7 drinks
per week.
Risk for the development of ALD
Time to develop ALD = to amount of alcohol
consumed

•Men: 60-80 gm/day for 10 years

•Women: 20-40 gm/day for 10 years


Alcoholic cirrhosis, develops ONLY in 10 to 20% of
those who are chronically heavy drinkers.
Loading…
Risk for the development of ALD
•Epidemiology

–Over 90% of chronic heavy drinkers will develop
steatosis

–10 to 20% will develop alcoholic hepatitis

–ALD cause death of 1 in 50 people in Scotland

–4 fold increase in deaths from ALD in past 30
years
Risk for the development of ALD
•Risk of liver disease
–Amount of alcohol consumed
–Genetic factors
–Female sex
–Obesity
–Chronic viral hepatitis
–Nutritional impairment
–drugs
Alcohol Metabolism and the Liver
•The liver is the principal organ for alcohol metabolism.
•The body naturally recognizes ethanol alcohol as a foreign, toxic
agent that can disrupt normal homeostasis.
•When we consume ethanol, it is rapidly absorbed by the upper
gastrointestinal tract.
•Ethanol is
–diffused throughout the body, but exposure is greatest to the liver, via the
main portal vein.
–metabolized by the body in the gastric mucosa and the liver. These organs
manage an enzyme referred to as alcohol dehydrogenase, which is used by
the body to oxidize ethanol and convert it into acetaldehyde and other
metabolites.
–Acetaldehyde ultimately is converted by the body into acetic acid, and then
acetate. Acetaldehyde affects protein synthesis.
Alcohol Metabolism and the Liver


•Alcohol’s metabolites, especially acetaldehyde, damage vital liver
cells because of the excessive generation of free radicals.


•Excessive amount of this type of free radical causes oxidative
stress, which results in the body’s inability to prevent and repair
hepatic damage and the destruction of deoxyribonucleic acid.
Alcohol Metabolism and the Liver
•In addition to the immediate damage of acetaldehyde and the free
radicals, the phagocytic cells of the liver, the Kupffer cells, also
mount an immune response.
•This response is the result of an increase in toxins in the blood that
leak from the intestinal wall and enter the blood stream because of
alcohol consumption.
•The activation of Kupffer cells is responsible for early ethanol-
induced liver injury that ultimately leads to the death of
hepatocytes.
•This damage results in the manifestation of alcoholic liver disease,
and eventually to the development of fibrosis, or scar tissue, within
the liver.

Alcohol Metabolism and the Liver
•Alcohol metabolism differs dramatically between sexes.
–Women are much more likely to suffer from liver damage than men as a
result of alcohol consumption. However, this phenomenon is not clearly
understood.

•In addition to sex, the incidence of liver damage depends on the
– individual’s ethnicity
–genetic predisposition
–nutritional state.
Alcohol and the Liver
•Physical examination :

–vary from normal to evidence of cirrhosis or
hepatic decompensation
•Abdominal wall collaterals (caput medusa),
•Ascites,
•Cutaneous telangiectasias,
•Digital clubbing,
•Dupuytren's contractures,
•Gynecomastia,
•Jaundice,
•Malnutrition ,
•Palmar erythema,
•Peripheral neuropathy,
Alcohol and the Liver
•Laboratory findings:

–serum AST (SGOT), ALT (SGPT), and
gammaglutamyl transferase (GGT) are often
abnormal in alcoholic liver disease

–disproportionate elevation of serum AST (SGOT)
compared to ALT (SGPT) ratio is usually greater
than 2.0

–absolute values of serum AST and ALT are almost
always less than 500 IU/L
Alcohol and the Liver

–Consumption of alcohol can lead to a variety of
histopathologic changes in the liver ranging from
steatosis to cirrhosis
• Steatosis,
•alcoholic hepatitis,
•cirrhosis

–The mechanism behind the development of ALD is not
completely understood, because it is estimated that
only 10% to 20% of alcoholics develop cirrhosis.

Alcoholic Liver Disease
•Signs and symptoms
–Steatosis:
•usually asymptomatic, hepatomegaly

–Alcoholic hepatitis:
•malaise, jaundice, tender hepatomegaly, fever, weight
loss, abdominal discomfort

–Cirrhosis:
•similar to other causes of cirrhosis.
•Hepatomegaly, splenomegaly, malaise, jaundice, weight
loss, ascites, signs of CLD
Alcoholic Liver Disease and
Alcoholic Cirrhosis
•Hepatic steatosis;

–commonly referred to as fatty liver, is a frequent diagnosis that is not
exclusive to patients suffering from ALD.

–Fatty liver is the accumulation of triglycerides in the hepatocytes.

–Fatty liver has been demonstrated in 90% to 100% of all heavy drinkers.

–Short-term exposure to 80 g of alcohol (about 8 beers) over several days can
produce hepatic changes consistent with fatty liver disease.

–Fatty liver may develop after a single large binge and does not predict progression to
hepatitis
Alcohol and the Liver
•ALCOHOLIC FATTY LIVER:
–Fatty liver disease can be reversed if alcohol
consumption is stopped or significantly reduced.
–progression to fibrosis or cirrhosis occurred only in
patients who continued to ingest alcohol

–there are often no clinical symptoms, so fatty
liver may be undiagnosed. The only
complaint may be mild tender
hepatomegaly.

Alcohol and the Liver
•ALCOHOLIC FATTY LIVER:
•Pathology:
– macrovesicular fatty infiltration
–inflammatory changes are minimal
–fatty liver is not pathognomonic of ethanol ingestion:
• starvation,
•fatty liver of pregnancy,
•drug toxicity (valproic acid, tetracycline,
•antiviral agents such as zidovudine and dideoxyinosine),
•nonalcoholic steatohepatitis,
•viral hepatitis, particularly hepatitis C virus,
•Reye's syndrome,
•inborn errors of metabolism (such as defects in mitochondrial beta
oxidation)
Alcoholic Liver Disease and
Alcoholic Cirrhosis
•Alcoholic hepatitis
–fatty liver with the development of hepatitis, referred to as steatohepatitis, has
been acknowledged as a precursor for the development of cirrhosis.

–Alcoholic hepatitis results directly from alcohol abuse and is observed in as
many as 35% of heavy drinkers.

–Like other forms of hepatitis, alcoholic hepatitis can be subclinical.

–Laboratory findings are more predictive if the disease has progressed.

–Approximately 40% of patients with alcoholic hepatitis who continue to
drink will develop alcoholic cirrhosis within 1 to 2 years.
Alcohol and the Liver

•ALCOHOLIC HEPATITIS:

8. Alcohol and the Liver

Alcohol and the Liver
• There is a broad spectrum of clinical and
laboratory findings in patients with alcoholic
liver disease, ranging from asymptomatic
fatty liver to alcoholic hepatitis to end-stage
liver failure with jaundice, coagulopathy, and
encephalopathy
Loading…
Alcohol and the Liver
• FINDINGS IN ALCOHOLIC LIVER
DISEASE

–moderate alcohol intake appears to have
cardiovascular benefits

– excessive alcohol intake can be associated with
significant social and physical consequences

–for the development of cirrhosis:
•requirement for 80 grams of ethanol daily for 10 to 20
Alcohol and the liver

•In 2009, WHO listed alcohol use as one of the
leading causes of the global burden of
disease and injury, surpassed only slightly by
childhood malnourishment and unsafe sex.


•This placed alcohol use ahead of unsafe water
and sanitation, hypertension, high cholesterol,
and tobacco use, and clearly affirms that
alcohol is the most widely abused substance
Loading…
Alcoholism and the Effects of
Alcohol

•In the United States, approximately 100 000
deaths per year are attributed to alcohol abuse.

•Alcohol use is an underlying cause of more
than 30 conditions and a definite contributing
factor to many more, including
–psychotic disorder
–alcoholic cardiomyopathy
–amnesic syndrome
–alcoholic liver disease.
Alcoholism and the Effects of
Alcohol

•The Mayo Clinic defined alcoholism as a
chronic disease in which the body becomes
reliant upon alcohol (ethanol).

•Furthermore, it has been referred to as a
syndrome that consists of 2 phases:
–problem drinking
and
–alcohol addiction.

Alcoholic Liver Disease
•Beverage Alcohol

–Beer 5%

–Wine 12%

–Hard Liquor 40%
(Brandy, wisky, Rum)

–Arrack 40 – 50%
Alcoholism and the Effects of
Alcohol
•A standard alcoholic beverage has been described as any drink that
contains 14 g of pure alcohol.
•Irrespective of what form of alcohol is consumed, the greatest risk
factor appears to be the quantity of alcohol consumed.
•The definition for low-risk drinking for men and women differs,
because
–women suffer from hepatic damage and cirrhosis with considerably smaller
amounts of alcohol consumption.
–A man should not drink more than 4 drinks per day and no more than 14 drinks
per week.
–A woman should not drink more than 3 drinks per day and no more than 7 drinks
per week.
Risk for the development of ALD
Time to develop ALD = to amount of alcohol
consumed

•Men: 60-80 gm/day for 10 years

•Women: 20-40 gm/day for 10 years


Alcoholic cirrhosis, develops ONLY in 10 to 20% of
those who are chronically heavy drinkers.
Loading…
Risk for the development of ALD
•Epidemiology

–Over 90% of chronic heavy drinkers will develop
steatosis

–10 to 20% will develop alcoholic hepatitis

–ALD cause death of 1 in 50 people in Scotland

–4 fold increase in deaths from ALD in past 30
years
Risk for the development of ALD
•Risk of liver disease
–Amount of alcohol consumed
–Genetic factors
–Female sex
–Obesity
–Chronic viral hepatitis
–Nutritional impairment
–drugs
Alcohol Metabolism and the Liver
•The liver is the principal organ for alcohol metabolism.
•The body naturally recognizes ethanol alcohol as a foreign, toxic
agent that can disrupt normal homeostasis.
•When we consume ethanol, it is rapidly absorbed by the upper
gastrointestinal tract.
•Ethanol is
–diffused throughout the body, but exposure is greatest to the liver, via the
main portal vein.
–metabolized by the body in the gastric mucosa and the liver. These organs
manage an enzyme referred to as alcohol dehydrogenase, which is used by
the body to oxidize ethanol and convert it into acetaldehyde and other
metabolites.
–Acetaldehyde ultimately is converted by the body into acetic acid, and then
acetate. Acetaldehyde affects protein synthesis.
Alcohol Metabolism and the Liver


•Alcohol’s metabolites, especially acetaldehyde, damage vital liver
cells because of the excessive generation of free radicals.


•Excessive amount of this type of free radical causes oxidative
stress, which results in the body’s inability to prevent and repair
hepatic damage and the destruction of deoxyribonucleic acid.
Alcohol Metabolism and the Liver
•In addition to the immediate damage of acetaldehyde and the free
radicals, the phagocytic cells of the liver, the Kupffer cells, also
mount an immune response.
•This response is the result of an increase in toxins in the blood that
leak from the intestinal wall and enter the blood stream because of
alcohol consumption.
•The activation of Kupffer cells is responsible for early ethanol-
induced liver injury that ultimately leads to the death of
hepatocytes.
•This damage results in the manifestation of alcoholic liver disease,
and eventually to the development of fibrosis, or scar tissue, within
the liver.

Alcohol Metabolism and the Liver
•Alcohol metabolism differs dramatically between sexes.
–Women are much more likely to suffer from liver damage than men as a
result of alcohol consumption. However, this phenomenon is not clearly
understood.

•In addition to sex, the incidence of liver damage depends on the
– individual’s ethnicity
–genetic predisposition
–nutritional state.
Alcohol and the Liver
•Physical examination :

–vary from normal to evidence of cirrhosis or
hepatic decompensation
•Abdominal wall collaterals (caput medusa),
•Ascites,
•Cutaneous telangiectasias,
•Digital clubbing,
•Dupuytren's contractures,
•Gynecomastia,
•Jaundice,
•Malnutrition ,
•Palmar erythema,
•Peripheral neuropathy,
Alcohol and the Liver
•Laboratory findings:

–serum AST (SGOT), ALT (SGPT), and
gammaglutamyl transferase (GGT) are often
abnormal in alcoholic liver disease

–disproportionate elevation of serum AST (SGOT)
compared to ALT (SGPT) ratio is usually greater
than 2.0

–absolute values of serum AST and ALT are almost
always less than 500 IU/L
Alcohol and the Liver

–Consumption of alcohol can lead to a variety of
histopathologic changes in the liver ranging from
steatosis to cirrhosis
• Steatosis,
•alcoholic hepatitis,
•cirrhosis

–The mechanism behind the development of ALD is not
completely understood, because it is estimated that
only 10% to 20% of alcoholics develop cirrhosis.

Alcoholic Liver Disease
•Signs and symptoms
–Steatosis:
•usually asymptomatic, hepatomegaly

–Alcoholic hepatitis:
•malaise, jaundice, tender hepatomegaly, fever, weight
loss, abdominal discomfort

–Cirrhosis:
•similar to other causes of cirrhosis.
•Hepatomegaly, splenomegaly, malaise, jaundice, weight
loss, ascites, signs of CLD
Alcoholic Liver Disease and
Alcoholic Cirrhosis
•Hepatic steatosis;

–commonly referred to as fatty liver, is a frequent diagnosis that is not
exclusive to patients suffering from ALD.

–Fatty liver is the accumulation of triglycerides in the hepatocytes.

–Fatty liver has been demonstrated in 90% to 100% of all heavy drinkers.

–Short-term exposure to 80 g of alcohol (about 8 beers) over several days can
produce hepatic changes consistent with fatty liver disease.

–Fatty liver may develop after a single large binge and does not predict progression to
hepatitis
Alcohol and the Liver
•ALCOHOLIC FATTY LIVER:
–Fatty liver disease can be reversed if alcohol
consumption is stopped or significantly reduced.
–progression to fibrosis or cirrhosis occurred only in
patients who continued to ingest alcohol

–there are often no clinical symptoms, so fatty
liver may be undiagnosed. The only
complaint may be mild tender
hepatomegaly.

Alcohol and the Liver
•ALCOHOLIC FATTY LIVER:
•Pathology:
– macrovesicular fatty infiltration
–inflammatory changes are minimal
–fatty liver is not pathognomonic of ethanol ingestion:
• starvation,
•fatty liver of pregnancy,
•drug toxicity (valproic acid, tetracycline,
•antiviral agents such as zidovudine and dideoxyinosine),
•nonalcoholic steatohepatitis,
•viral hepatitis, particularly hepatitis C virus,
•Reye's syndrome,
•inborn errors of metabolism (such as defects in mitochondrial beta
oxidation)
Alcoholic Liver Disease and
Alcoholic Cirrhosis
•Alcoholic hepatitis
–fatty liver with the development of hepatitis, referred to as steatohepatitis, has
been acknowledged as a precursor for the development of cirrhosis.

–Alcoholic hepatitis results directly from alcohol abuse and is observed in as
many as 35% of heavy drinkers.

–Like other forms of hepatitis, alcoholic hepatitis can be subclinical.

–Laboratory findings are more predictive if the disease has progressed.

–Approximately 40% of patients with alcoholic hepatitis who continue to
drink will develop alcoholic cirrhosis within 1 to 2 years.
Alcohol and the Liver

•ALCOHOLIC HEPATITIS:

9. Alcohol and the Liver

Alcohol and the Liver
• There is a broad spectrum of clinical and
laboratory findings in patients with alcoholic
liver disease, ranging from asymptomatic
fatty liver to alcoholic hepatitis to end-stage
liver failure with jaundice, coagulopathy, and
encephalopathy
Loading…
Alcohol and the Liver
• FINDINGS IN ALCOHOLIC LIVER
DISEASE

–moderate alcohol intake appears to have
cardiovascular benefits

– excessive alcohol intake can be associated with
significant social and physical consequences

–for the development of cirrhosis:
•requirement for 80 grams of ethanol daily for 10 to 20
Alcohol and the liver

•In 2009, WHO listed alcohol use as one of the
leading causes of the global burden of
disease and injury, surpassed only slightly by
childhood malnourishment and unsafe sex.


•This placed alcohol use ahead of unsafe water
and sanitation, hypertension, high cholesterol,
and tobacco use, and clearly affirms that
alcohol is the most widely abused substance
Loading…
Alcoholism and the Effects of
Alcohol

•In the United States, approximately 100 000
deaths per year are attributed to alcohol abuse.

•Alcohol use is an underlying cause of more
than 30 conditions and a definite contributing
factor to many more, including
–psychotic disorder
–alcoholic cardiomyopathy
–amnesic syndrome
–alcoholic liver disease.
Alcoholism and the Effects of
Alcohol

•The Mayo Clinic defined alcoholism as a
chronic disease in which the body becomes
reliant upon alcohol (ethanol).

•Furthermore, it has been referred to as a
syndrome that consists of 2 phases:
–problem drinking
and
–alcohol addiction.

Alcoholic Liver Disease
•Beverage Alcohol

–Beer 5%

–Wine 12%

–Hard Liquor 40%
(Brandy, wisky, Rum)

–Arrack 40 – 50%
Alcoholism and the Effects of
Alcohol
•A standard alcoholic beverage has been described as any drink that
contains 14 g of pure alcohol.
•Irrespective of what form of alcohol is consumed, the greatest risk
factor appears to be the quantity of alcohol consumed.
•The definition for low-risk drinking for men and women differs,
because
–women suffer from hepatic damage and cirrhosis with considerably smaller
amounts of alcohol consumption.
–A man should not drink more than 4 drinks per day and no more than 14 drinks
per week.
–A woman should not drink more than 3 drinks per day and no more than 7 drinks
per week.
Risk for the development of ALD
Time to develop ALD = to amount of alcohol
consumed

•Men: 60-80 gm/day for 10 years

•Women: 20-40 gm/day for 10 years


Alcoholic cirrhosis, develops ONLY in 10 to 20% of
those who are chronically heavy drinkers.
Loading…
Risk for the development of ALD
•Epidemiology

–Over 90% of chronic heavy drinkers will develop
steatosis

–10 to 20% will develop alcoholic hepatitis

–ALD cause death of 1 in 50 people in Scotland

–4 fold increase in deaths from ALD in past 30
years
Risk for the development of ALD
•Risk of liver disease
–Amount of alcohol consumed
–Genetic factors
–Female sex
–Obesity
–Chronic viral hepatitis
–Nutritional impairment
–drugs
Alcohol Metabolism and the Liver
•The liver is the principal organ for alcohol metabolism.
•The body naturally recognizes ethanol alcohol as a foreign, toxic
agent that can disrupt normal homeostasis.
•When we consume ethanol, it is rapidly absorbed by the upper
gastrointestinal tract.
•Ethanol is
–diffused throughout the body, but exposure is greatest to the liver, via the
main portal vein.
–metabolized by the body in the gastric mucosa and the liver. These organs
manage an enzyme referred to as alcohol dehydrogenase, which is used by
the body to oxidize ethanol and convert it into acetaldehyde and other
metabolites.
–Acetaldehyde ultimately is converted by the body into acetic acid, and then
acetate. Acetaldehyde affects protein synthesis.
Alcohol Metabolism and the Liver


•Alcohol’s metabolites, especially acetaldehyde, damage vital liver
cells because of the excessive generation of free radicals.


•Excessive amount of this type of free radical causes oxidative
stress, which results in the body’s inability to prevent and repair
hepatic damage and the destruction of deoxyribonucleic acid.
Alcohol Metabolism and the Liver
•In addition to the immediate damage of acetaldehyde and the free
radicals, the phagocytic cells of the liver, the Kupffer cells, also
mount an immune response.
•This response is the result of an increase in toxins in the blood that
leak from the intestinal wall and enter the blood stream because of
alcohol consumption.
•The activation of Kupffer cells is responsible for early ethanol-
induced liver injury that ultimately leads to the death of
hepatocytes.
•This damage results in the manifestation of alcoholic liver disease,
and eventually to the development of fibrosis, or scar tissue, within
the liver.

Alcohol Metabolism and the Liver
•Alcohol metabolism differs dramatically between sexes.
–Women are much more likely to suffer from liver damage than men as a
result of alcohol consumption. However, this phenomenon is not clearly
understood.

•In addition to sex, the incidence of liver damage depends on the
– individual’s ethnicity
–genetic predisposition
–nutritional state.
Alcohol and the Liver
•Physical examination :

–vary from normal to evidence of cirrhosis or
hepatic decompensation
•Abdominal wall collaterals (caput medusa),
•Ascites,
•Cutaneous telangiectasias,
•Digital clubbing,
•Dupuytren's contractures,
•Gynecomastia,
•Jaundice,
•Malnutrition ,
•Palmar erythema,
•Peripheral neuropathy,
Alcohol and the Liver
•Laboratory findings:

–serum AST (SGOT), ALT (SGPT), and
gammaglutamyl transferase (GGT) are often
abnormal in alcoholic liver disease

–disproportionate elevation of serum AST (SGOT)
compared to ALT (SGPT) ratio is usually greater
than 2.0

–absolute values of serum AST and ALT are almost
always less than 500 IU/L
Alcohol and the Liver

–Consumption of alcohol can lead to a variety of
histopathologic changes in the liver ranging from
steatosis to cirrhosis
• Steatosis,
•alcoholic hepatitis,
•cirrhosis

–The mechanism behind the development of ALD is not
completely understood, because it is estimated that
only 10% to 20% of alcoholics develop cirrhosis.

Alcoholic Liver Disease
•Signs and symptoms
–Steatosis:
•usually asymptomatic, hepatomegaly

–Alcoholic hepatitis:
•malaise, jaundice, tender hepatomegaly, fever, weight
loss, abdominal discomfort

–Cirrhosis:
•similar to other causes of cirrhosis.
•Hepatomegaly, splenomegaly, malaise, jaundice, weight
loss, ascites, signs of CLD
Alcoholic Liver Disease and
Alcoholic Cirrhosis
•Hepatic steatosis;

–commonly referred to as fatty liver, is a frequent diagnosis that is not
exclusive to patients suffering from ALD.

–Fatty liver is the accumulation of triglycerides in the hepatocytes.

–Fatty liver has been demonstrated in 90% to 100% of all heavy drinkers.

–Short-term exposure to 80 g of alcohol (about 8 beers) over several days can
produce hepatic changes consistent with fatty liver disease.

–Fatty liver may develop after a single large binge and does not predict progression to
hepatitis
Alcohol and the Liver
•ALCOHOLIC FATTY LIVER:
–Fatty liver disease can be reversed if alcohol
consumption is stopped or significantly reduced.
–progression to fibrosis or cirrhosis occurred only in
patients who continued to ingest alcohol

–there are often no clinical symptoms, so fatty
liver may be undiagnosed. The only
complaint may be mild tender
hepatomegaly.

Alcohol and the Liver
•ALCOHOLIC FATTY LIVER:
•Pathology:
– macrovesicular fatty infiltration
–inflammatory changes are minimal
–fatty liver is not pathognomonic of ethanol ingestion:
• starvation,
•fatty liver of pregnancy,
•drug toxicity (valproic acid, tetracycline,
•antiviral agents such as zidovudine and dideoxyinosine),
•nonalcoholic steatohepatitis,
•viral hepatitis, particularly hepatitis C virus,
•Reye's syndrome,
•inborn errors of metabolism (such as defects in mitochondrial beta
oxidation)
Alcoholic Liver Disease and
Alcoholic Cirrhosis
•Alcoholic hepatitis
–fatty liver with the development of hepatitis, referred to as steatohepatitis, has
been acknowledged as a precursor for the development of cirrhosis.

–Alcoholic hepatitis results directly from alcohol abuse and is observed in as
many as 35% of heavy drinkers.

–Like other forms of hepatitis, alcoholic hepatitis can be subclinical.

–Laboratory findings are more predictive if the disease has progressed.

–Approximately 40% of patients with alcoholic hepatitis who continue to
drink will develop alcoholic cirrhosis within 1 to 2 years.
Alcohol and the Liver

•ALCOHOLIC HEPATITIS:

10. Alcohol and the Liver

Alcohol and the Liver
• There is a broad spectrum of clinical and
laboratory findings in patients with alcoholic
liver disease, ranging from asymptomatic
fatty liver to alcoholic hepatitis to end-stage
liver failure with jaundice, coagulopathy, and
encephalopathy
Loading…
Alcohol and the Liver
• FINDINGS IN ALCOHOLIC LIVER
DISEASE

–moderate alcohol intake appears to have
cardiovascular benefits

– excessive alcohol intake can be associated with
significant social and physical consequences

–for the development of cirrhosis:
•requirement for 80 grams of ethanol daily for 10 to 20
Alcohol and the liver

•In 2009, WHO listed alcohol use as one of the
leading causes of the global burden of
disease and injury, surpassed only slightly by
childhood malnourishment and unsafe sex.


•This placed alcohol use ahead of unsafe water
and sanitation, hypertension, high cholesterol,
and tobacco use, and clearly affirms that
alcohol is the most widely abused substance
Loading…
Alcoholism and the Effects of
Alcohol

•In the United States, approximately 100 000
deaths per year are attributed to alcohol abuse.

•Alcohol use is an underlying cause of more
than 30 conditions and a definite contributing
factor to many more, including
–psychotic disorder
–alcoholic cardiomyopathy
–amnesic syndrome
–alcoholic liver disease.
Alcoholism and the Effects of
Alcohol

•The Mayo Clinic defined alcoholism as a
chronic disease in which the body becomes
reliant upon alcohol (ethanol).

•Furthermore, it has been referred to as a
syndrome that consists of 2 phases:
–problem drinking
and
–alcohol addiction.

Alcoholic Liver Disease
•Beverage Alcohol

–Beer 5%

–Wine 12%

–Hard Liquor 40%
(Brandy, wisky, Rum)

–Arrack 40 – 50%
Alcoholism and the Effects of
Alcohol
•A standard alcoholic beverage has been described as any drink that
contains 14 g of pure alcohol.
•Irrespective of what form of alcohol is consumed, the greatest risk
factor appears to be the quantity of alcohol consumed.
•The definition for low-risk drinking for men and women differs,
because
–women suffer from hepatic damage and cirrhosis with considerably smaller
amounts of alcohol consumption.
–A man should not drink more than 4 drinks per day and no more than 14 drinks
per week.
–A woman should not drink more than 3 drinks per day and no more than 7 drinks
per week.
Risk for the development of ALD
Time to develop ALD = to amount of alcohol
consumed

•Men: 60-80 gm/day for 10 years

•Women: 20-40 gm/day for 10 years


Alcoholic cirrhosis, develops ONLY in 10 to 20% of
those who are chronically heavy drinkers.
Loading…
Risk for the development of ALD
•Epidemiology

–Over 90% of chronic heavy drinkers will develop
steatosis

–10 to 20% will develop alcoholic hepatitis

–ALD cause death of 1 in 50 people in Scotland

–4 fold increase in deaths from ALD in past 30
years
Risk for the development of ALD
•Risk of liver disease
–Amount of alcohol consumed
–Genetic factors
–Female sex
–Obesity
–Chronic viral hepatitis
–Nutritional impairment
–drugs
Alcohol Metabolism and the Liver
•The liver is the principal organ for alcohol metabolism.
•The body naturally recognizes ethanol alcohol as a foreign, toxic
agent that can disrupt normal homeostasis.
•When we consume ethanol, it is rapidly absorbed by the upper
gastrointestinal tract.
•Ethanol is
–diffused throughout the body, but exposure is greatest to the liver, via the
main portal vein.
–metabolized by the body in the gastric mucosa and the liver. These organs
manage an enzyme referred to as alcohol dehydrogenase, which is used by
the body to oxidize ethanol and convert it into acetaldehyde and other
metabolites.
–Acetaldehyde ultimately is converted by the body into acetic acid, and then
acetate. Acetaldehyde affects protein synthesis.
Alcohol Metabolism and the Liver


•Alcohol’s metabolites, especially acetaldehyde, damage vital liver
cells because of the excessive generation of free radicals.


•Excessive amount of this type of free radical causes oxidative
stress, which results in the body’s inability to prevent and repair
hepatic damage and the destruction of deoxyribonucleic acid.
Alcohol Metabolism and the Liver
•In addition to the immediate damage of acetaldehyde and the free
radicals, the phagocytic cells of the liver, the Kupffer cells, also
mount an immune response.
•This response is the result of an increase in toxins in the blood that
leak from the intestinal wall and enter the blood stream because of
alcohol consumption.
•The activation of Kupffer cells is responsible for early ethanol-
induced liver injury that ultimately leads to the death of
hepatocytes.
•This damage results in the manifestation of alcoholic liver disease,
and eventually to the development of fibrosis, or scar tissue, within
the liver.

Alcohol Metabolism and the Liver
•Alcohol metabolism differs dramatically between sexes.
–Women are much more likely to suffer from liver damage than men as a
result of alcohol consumption. However, this phenomenon is not clearly
understood.

•In addition to sex, the incidence of liver damage depends on the
– individual’s ethnicity
–genetic predisposition
–nutritional state.
Alcohol and the Liver
•Physical examination :

–vary from normal to evidence of cirrhosis or
hepatic decompensation
•Abdominal wall collaterals (caput medusa),
•Ascites,
•Cutaneous telangiectasias,
•Digital clubbing,
•Dupuytren's contractures,
•Gynecomastia,
•Jaundice,
•Malnutrition ,
•Palmar erythema,
•Peripheral neuropathy,
Alcohol and the Liver
•Laboratory findings:

–serum AST (SGOT), ALT (SGPT), and
gammaglutamyl transferase (GGT) are often
abnormal in alcoholic liver disease

–disproportionate elevation of serum AST (SGOT)
compared to ALT (SGPT) ratio is usually greater
than 2.0

–absolute values of serum AST and ALT are almost
always less than 500 IU/L
Alcohol and the Liver

–Consumption of alcohol can lead to a variety of
histopathologic changes in the liver ranging from
steatosis to cirrhosis
• Steatosis,
•alcoholic hepatitis,
•cirrhosis

–The mechanism behind the development of ALD is not
completely understood, because it is estimated that
only 10% to 20% of alcoholics develop cirrhosis.

Alcoholic Liver Disease
•Signs and symptoms
–Steatosis:
•usually asymptomatic, hepatomegaly

–Alcoholic hepatitis:
•malaise, jaundice, tender hepatomegaly, fever, weight
loss, abdominal discomfort

–Cirrhosis:
•similar to other causes of cirrhosis.
•Hepatomegaly, splenomegaly, malaise, jaundice, weight
loss, ascites, signs of CLD
Alcoholic Liver Disease and
Alcoholic Cirrhosis
•Hepatic steatosis;

–commonly referred to as fatty liver, is a frequent diagnosis that is not
exclusive to patients suffering from ALD.

–Fatty liver is the accumulation of triglycerides in the hepatocytes.

–Fatty liver has been demonstrated in 90% to 100% of all heavy drinkers.

–Short-term exposure to 80 g of alcohol (about 8 beers) over several days can
produce hepatic changes consistent with fatty liver disease.

–Fatty liver may develop after a single large binge and does not predict progression to
hepatitis
Alcohol and the Liver
•ALCOHOLIC FATTY LIVER:
–Fatty liver disease can be reversed if alcohol
consumption is stopped or significantly reduced.
–progression to fibrosis or cirrhosis occurred only in
patients who continued to ingest alcohol

–there are often no clinical symptoms, so fatty
liver may be undiagnosed. The only
complaint may be mild tender
hepatomegaly.

Alcohol and the Liver
•ALCOHOLIC FATTY LIVER:
•Pathology:
– macrovesicular fatty infiltration
–inflammatory changes are minimal
–fatty liver is not pathognomonic of ethanol ingestion:
• starvation,
•fatty liver of pregnancy,
•drug toxicity (valproic acid, tetracycline,
•antiviral agents such as zidovudine and dideoxyinosine),
•nonalcoholic steatohepatitis,
•viral hepatitis, particularly hepatitis C virus,
•Reye's syndrome,
•inborn errors of metabolism (such as defects in mitochondrial beta
oxidation)
Alcoholic Liver Disease and
Alcoholic Cirrhosis
•Alcoholic hepatitis
–fatty liver with the development of hepatitis, referred to as steatohepatitis, has
been acknowledged as a precursor for the development of cirrhosis.

–Alcoholic hepatitis results directly from alcohol abuse and is observed in as
many as 35% of heavy drinkers.

–Like other forms of hepatitis, alcoholic hepatitis can be subclinical.

–Laboratory findings are more predictive if the disease has progressed.

–Approximately 40% of patients with alcoholic hepatitis who continue to
drink will develop alcoholic cirrhosis within 1 to 2 years.
Alcohol and the Liver

•ALCOHOLIC HEPATITIS:

11. Alcohol and the Liver

Alcohol and the Liver
• There is a broad spectrum of clinical and
laboratory findings in patients with alcoholic
liver disease, ranging from asymptomatic
fatty liver to alcoholic hepatitis to end-stage
liver failure with jaundice, coagulopathy, and
encephalopathy
Loading…
Alcohol and the Liver
• FINDINGS IN ALCOHOLIC LIVER
DISEASE

–moderate alcohol intake appears to have
cardiovascular benefits

– excessive alcohol intake can be associated with
significant social and physical consequences

–for the development of cirrhosis:
•requirement for 80 grams of ethanol daily for 10 to 20
Alcohol and the liver

•In 2009, WHO listed alcohol use as one of the
leading causes of the global burden of
disease and injury, surpassed only slightly by
childhood malnourishment and unsafe sex.


•This placed alcohol use ahead of unsafe water
and sanitation, hypertension, high cholesterol,
and tobacco use, and clearly affirms that
alcohol is the most widely abused substance
Loading…
Alcoholism and the Effects of
Alcohol

•In the United States, approximately 100 000
deaths per year are attributed to alcohol abuse.

•Alcohol use is an underlying cause of more
than 30 conditions and a definite contributing
factor to many more, including
–psychotic disorder
–alcoholic cardiomyopathy
–amnesic syndrome
–alcoholic liver disease.
Alcoholism and the Effects of
Alcohol

•The Mayo Clinic defined alcoholism as a
chronic disease in which the body becomes
reliant upon alcohol (ethanol).

•Furthermore, it has been referred to as a
syndrome that consists of 2 phases:
–problem drinking
and
–alcohol addiction.

Alcoholic Liver Disease
•Beverage Alcohol

–Beer 5%

–Wine 12%

–Hard Liquor 40%
(Brandy, wisky, Rum)

–Arrack 40 – 50%
Alcoholism and the Effects of
Alcohol
•A standard alcoholic beverage has been described as any drink that
contains 14 g of pure alcohol.
•Irrespective of what form of alcohol is consumed, the greatest risk
factor appears to be the quantity of alcohol consumed.
•The definition for low-risk drinking for men and women differs,
because
–women suffer from hepatic damage and cirrhosis with considerably smaller
amounts of alcohol consumption.
–A man should not drink more than 4 drinks per day and no more than 14 drinks
per week.
–A woman should not drink more than 3 drinks per day and no more than 7 drinks
per week.
Risk for the development of ALD
Time to develop ALD = to amount of alcohol
consumed

•Men: 60-80 gm/day for 10 years

•Women: 20-40 gm/day for 10 years


Alcoholic cirrhosis, develops ONLY in 10 to 20% of
those who are chronically heavy drinkers.
Loading…
Risk for the development of ALD
•Epidemiology

–Over 90% of chronic heavy drinkers will develop
steatosis

–10 to 20% will develop alcoholic hepatitis

–ALD cause death of 1 in 50 people in Scotland

–4 fold increase in deaths from ALD in past 30
years
Risk for the development of ALD
•Risk of liver disease
–Amount of alcohol consumed
–Genetic factors
–Female sex
–Obesity
–Chronic viral hepatitis
–Nutritional impairment
–drugs
Alcohol Metabolism and the Liver
•The liver is the principal organ for alcohol metabolism.
•The body naturally recognizes ethanol alcohol as a foreign, toxic
agent that can disrupt normal homeostasis.
•When we consume ethanol, it is rapidly absorbed by the upper
gastrointestinal tract.
•Ethanol is
–diffused throughout the body, but exposure is greatest to the liver, via the
main portal vein.
–metabolized by the body in the gastric mucosa and the liver. These organs
manage an enzyme referred to as alcohol dehydrogenase, which is used by
the body to oxidize ethanol and convert it into acetaldehyde and other
metabolites.
–Acetaldehyde ultimately is converted by the body into acetic acid, and then
acetate. Acetaldehyde affects protein synthesis.
Alcohol Metabolism and the Liver


•Alcohol’s metabolites, especially acetaldehyde, damage vital liver
cells because of the excessive generation of free radicals.


•Excessive amount of this type of free radical causes oxidative
stress, which results in the body’s inability to prevent and repair
hepatic damage and the destruction of deoxyribonucleic acid.
Alcohol Metabolism and the Liver
•In addition to the immediate damage of acetaldehyde and the free
radicals, the phagocytic cells of the liver, the Kupffer cells, also
mount an immune response.
•This response is the result of an increase in toxins in the blood that
leak from the intestinal wall and enter the blood stream because of
alcohol consumption.
•The activation of Kupffer cells is responsible for early ethanol-
induced liver injury that ultimately leads to the death of
hepatocytes.
•This damage results in the manifestation of alcoholic liver disease,
and eventually to the development of fibrosis, or scar tissue, within
the liver.

Alcohol Metabolism and the Liver
•Alcohol metabolism differs dramatically between sexes.
–Women are much more likely to suffer from liver damage than men as a
result of alcohol consumption. However, this phenomenon is not clearly
understood.

•In addition to sex, the incidence of liver damage depends on the
– individual’s ethnicity
–genetic predisposition
–nutritional state.
Alcohol and the Liver
•Physical examination :

–vary from normal to evidence of cirrhosis or
hepatic decompensation
•Abdominal wall collaterals (caput medusa),
•Ascites,
•Cutaneous telangiectasias,
•Digital clubbing,
•Dupuytren's contractures,
•Gynecomastia,
•Jaundice,
•Malnutrition ,
•Palmar erythema,
•Peripheral neuropathy,
Alcohol and the Liver
•Laboratory findings:

–serum AST (SGOT), ALT (SGPT), and
gammaglutamyl transferase (GGT) are often
abnormal in alcoholic liver disease

–disproportionate elevation of serum AST (SGOT)
compared to ALT (SGPT) ratio is usually greater
than 2.0

–absolute values of serum AST and ALT are almost
always less than 500 IU/L
Alcohol and the Liver

–Consumption of alcohol can lead to a variety of
histopathologic changes in the liver ranging from
steatosis to cirrhosis
• Steatosis,
•alcoholic hepatitis,
•cirrhosis

–The mechanism behind the development of ALD is not
completely understood, because it is estimated that
only 10% to 20% of alcoholics develop cirrhosis.

Alcoholic Liver Disease
•Signs and symptoms
–Steatosis:
•usually asymptomatic, hepatomegaly

–Alcoholic hepatitis:
•malaise, jaundice, tender hepatomegaly, fever, weight
loss, abdominal discomfort

–Cirrhosis:
•similar to other causes of cirrhosis.
•Hepatomegaly, splenomegaly, malaise, jaundice, weight
loss, ascites, signs of CLD
Alcoholic Liver Disease and
Alcoholic Cirrhosis
•Hepatic steatosis;

–commonly referred to as fatty liver, is a frequent diagnosis that is not
exclusive to patients suffering from ALD.

–Fatty liver is the accumulation of triglycerides in the hepatocytes.

–Fatty liver has been demonstrated in 90% to 100% of all heavy drinkers.

–Short-term exposure to 80 g of alcohol (about 8 beers) over several days can
produce hepatic changes consistent with fatty liver disease.

–Fatty liver may develop after a single large binge and does not predict progression to
hepatitis
Alcohol and the Liver
•ALCOHOLIC FATTY LIVER:
–Fatty liver disease can be reversed if alcohol
consumption is stopped or significantly reduced.
–progression to fibrosis or cirrhosis occurred only in
patients who continued to ingest alcohol

–there are often no clinical symptoms, so fatty
liver may be undiagnosed. The only
complaint may be mild tender
hepatomegaly.

Alcohol and the Liver
•ALCOHOLIC FATTY LIVER:
•Pathology:
– macrovesicular fatty infiltration
–inflammatory changes are minimal
–fatty liver is not pathognomonic of ethanol ingestion:
• starvation,
•fatty liver of pregnancy,
•drug toxicity (valproic acid, tetracycline,
•antiviral agents such as zidovudine and dideoxyinosine),
•nonalcoholic steatohepatitis,
•viral hepatitis, particularly hepatitis C virus,
•Reye's syndrome,
•inborn errors of metabolism (such as defects in mitochondrial beta
oxidation)
Alcoholic Liver Disease and
Alcoholic Cirrhosis
•Alcoholic hepatitis
–fatty liver with the development of hepatitis, referred to as steatohepatitis, has
been acknowledged as a precursor for the development of cirrhosis.

–Alcoholic hepatitis results directly from alcohol abuse and is observed in as
many as 35% of heavy drinkers.

–Like other forms of hepatitis, alcoholic hepatitis can be subclinical.

–Laboratory findings are more predictive if the disease has progressed.

–Approximately 40% of patients with alcoholic hepatitis who continue to
drink will develop alcoholic cirrhosis within 1 to 2 years.
Alcohol and the Liver

•ALCOHOLIC HEPATITIS:

12. Alcohol and the Liver

Alcohol and the Liver
• There is a broad spectrum of clinical and
laboratory findings in patients with alcoholic
liver disease, ranging from asymptomatic
fatty liver to alcoholic hepatitis to end-stage
liver failure with jaundice, coagulopathy, and
encephalopathy
Loading…
Alcohol and the Liver
• FINDINGS IN ALCOHOLIC LIVER
DISEASE

–moderate alcohol intake appears to have
cardiovascular benefits

– excessive alcohol intake can be associated with
significant social and physical consequences

–for the development of cirrhosis:
•requirement for 80 grams of ethanol daily for 10 to 20
Alcohol and the liver

•In 2009, WHO listed alcohol use as one of the
leading causes of the global burden of
disease and injury, surpassed only slightly by
childhood malnourishment and unsafe sex.


•This placed alcohol use ahead of unsafe water
and sanitation, hypertension, high cholesterol,
and tobacco use, and clearly affirms that
alcohol is the most widely abused substance
Loading…
Alcoholism and the Effects of
Alcohol

•In the United States, approximately 100 000
deaths per year are attributed to alcohol abuse.

•Alcohol use is an underlying cause of more
than 30 conditions and a definite contributing
factor to many more, including
–psychotic disorder
–alcoholic cardiomyopathy
–amnesic syndrome
–alcoholic liver disease.
Alcoholism and the Effects of
Alcohol

•The Mayo Clinic defined alcoholism as a
chronic disease in which the body becomes
reliant upon alcohol (ethanol).

•Furthermore, it has been referred to as a
syndrome that consists of 2 phases:
–problem drinking
and
–alcohol addiction.

Alcoholic Liver Disease
•Beverage Alcohol

–Beer 5%

–Wine 12%

–Hard Liquor 40%
(Brandy, wisky, Rum)

–Arrack 40 – 50%
Alcoholism and the Effects of
Alcohol
•A standard alcoholic beverage has been described as any drink that
contains 14 g of pure alcohol.
•Irrespective of what form of alcohol is consumed, the greatest risk
factor appears to be the quantity of alcohol consumed.
•The definition for low-risk drinking for men and women differs,
because
–women suffer from hepatic damage and cirrhosis with considerably smaller
amounts of alcohol consumption.
–A man should not drink more than 4 drinks per day and no more than 14 drinks
per week.
–A woman should not drink more than 3 drinks per day and no more than 7 drinks
per week.
Risk for the development of ALD
Time to develop ALD = to amount of alcohol
consumed

•Men: 60-80 gm/day for 10 years

•Women: 20-40 gm/day for 10 years


Alcoholic cirrhosis, develops ONLY in 10 to 20% of
those who are chronically heavy drinkers.
Loading…
Risk for the development of ALD
•Epidemiology

–Over 90% of chronic heavy drinkers will develop
steatosis

–10 to 20% will develop alcoholic hepatitis

–ALD cause death of 1 in 50 people in Scotland

–4 fold increase in deaths from ALD in past 30
years
Risk for the development of ALD
•Risk of liver disease
–Amount of alcohol consumed
–Genetic factors
–Female sex
–Obesity
–Chronic viral hepatitis
–Nutritional impairment
–drugs
Alcohol Metabolism and the Liver
•The liver is the principal organ for alcohol metabolism.
•The body naturally recognizes ethanol alcohol as a foreign, toxic
agent that can disrupt normal homeostasis.
•When we consume ethanol, it is rapidly absorbed by the upper
gastrointestinal tract.
•Ethanol is
–diffused throughout the body, but exposure is greatest to the liver, via the
main portal vein.
–metabolized by the body in the gastric mucosa and the liver. These organs
manage an enzyme referred to as alcohol dehydrogenase, which is used by
the body to oxidize ethanol and convert it into acetaldehyde and other
metabolites.
–Acetaldehyde ultimately is converted by the body into acetic acid, and then
acetate. Acetaldehyde affects protein synthesis.
Alcohol Metabolism and the Liver


•Alcohol’s metabolites, especially acetaldehyde, damage vital liver
cells because of the excessive generation of free radicals.


•Excessive amount of this type of free radical causes oxidative
stress, which results in the body’s inability to prevent and repair
hepatic damage and the destruction of deoxyribonucleic acid.
Alcohol Metabolism and the Liver
•In addition to the immediate damage of acetaldehyde and the free
radicals, the phagocytic cells of the liver, the Kupffer cells, also
mount an immune response.
•This response is the result of an increase in toxins in the blood that
leak from the intestinal wall and enter the blood stream because of
alcohol consumption.
•The activation of Kupffer cells is responsible for early ethanol-
induced liver injury that ultimately leads to the death of
hepatocytes.
•This damage results in the manifestation of alcoholic liver disease,
and eventually to the development of fibrosis, or scar tissue, within
the liver.

Alcohol Metabolism and the Liver
•Alcohol metabolism differs dramatically between sexes.
–Women are much more likely to suffer from liver damage than men as a
result of alcohol consumption. However, this phenomenon is not clearly
understood.

•In addition to sex, the incidence of liver damage depends on the
– individual’s ethnicity
–genetic predisposition
–nutritional state.
Alcohol and the Liver
•Physical examination :

–vary from normal to evidence of cirrhosis or
hepatic decompensation
•Abdominal wall collaterals (caput medusa),
•Ascites,
•Cutaneous telangiectasias,
•Digital clubbing,
•Dupuytren's contractures,
•Gynecomastia,
•Jaundice,
•Malnutrition ,
•Palmar erythema,
•Peripheral neuropathy,
Alcohol and the Liver
•Laboratory findings:

–serum AST (SGOT), ALT (SGPT), and
gammaglutamyl transferase (GGT) are often
abnormal in alcoholic liver disease

–disproportionate elevation of serum AST (SGOT)
compared to ALT (SGPT) ratio is usually greater
than 2.0

–absolute values of serum AST and ALT are almost
always less than 500 IU/L
Alcohol and the Liver

–Consumption of alcohol can lead to a variety of
histopathologic changes in the liver ranging from
steatosis to cirrhosis
• Steatosis,
•alcoholic hepatitis,
•cirrhosis

–The mechanism behind the development of ALD is not
completely understood, because it is estimated that
only 10% to 20% of alcoholics develop cirrhosis.

Alcoholic Liver Disease
•Signs and symptoms
–Steatosis:
•usually asymptomatic, hepatomegaly

–Alcoholic hepatitis:
•malaise, jaundice, tender hepatomegaly, fever, weight
loss, abdominal discomfort

–Cirrhosis:
•similar to other causes of cirrhosis.
•Hepatomegaly, splenomegaly, malaise, jaundice, weight
loss, ascites, signs of CLD
Alcoholic Liver Disease and
Alcoholic Cirrhosis
•Hepatic steatosis;

–commonly referred to as fatty liver, is a frequent diagnosis that is not
exclusive to patients suffering from ALD.

–Fatty liver is the accumulation of triglycerides in the hepatocytes.

–Fatty liver has been demonstrated in 90% to 100% of all heavy drinkers.

–Short-term exposure to 80 g of alcohol (about 8 beers) over several days can
produce hepatic changes consistent with fatty liver disease.

–Fatty liver may develop after a single large binge and does not predict progression to
hepatitis
Alcohol and the Liver
•ALCOHOLIC FATTY LIVER:
–Fatty liver disease can be reversed if alcohol
consumption is stopped or significantly reduced.
–progression to fibrosis or cirrhosis occurred only in
patients who continued to ingest alcohol

–there are often no clinical symptoms, so fatty
liver may be undiagnosed. The only
complaint may be mild tender
hepatomegaly.

Alcohol and the Liver
•ALCOHOLIC FATTY LIVER:
•Pathology:
– macrovesicular fatty infiltration
–inflammatory changes are minimal
–fatty liver is not pathognomonic of ethanol ingestion:
• starvation,
•fatty liver of pregnancy,
•drug toxicity (valproic acid, tetracycline,
•antiviral agents such as zidovudine and dideoxyinosine),
•nonalcoholic steatohepatitis,
•viral hepatitis, particularly hepatitis C virus,
•Reye's syndrome,
•inborn errors of metabolism (such as defects in mitochondrial beta
oxidation)
Alcoholic Liver Disease and
Alcoholic Cirrhosis
•Alcoholic hepatitis
–fatty liver with the development of hepatitis, referred to as steatohepatitis, has
been acknowledged as a precursor for the development of cirrhosis.

–Alcoholic hepatitis results directly from alcohol abuse and is observed in as
many as 35% of heavy drinkers.

–Like other forms of hepatitis, alcoholic hepatitis can be subclinical.

–Laboratory findings are more predictive if the disease has progressed.

–Approximately 40% of patients with alcoholic hepatitis who continue to
drink will develop alcoholic cirrhosis within 1 to 2 years.
Alcohol and the Liver

•ALCOHOLIC HEPATITIS:

13. Alcohol and the Liver

Alcohol and the Liver
• There is a broad spectrum of clinical and
laboratory findings in patients with alcoholic
liver disease, ranging from asymptomatic
fatty liver to alcoholic hepatitis to end-stage
liver failure with jaundice, coagulopathy, and
encephalopathy
Loading…
Alcohol and the Liver
• FINDINGS IN ALCOHOLIC LIVER
DISEASE

–moderate alcohol intake appears to have
cardiovascular benefits

– excessive alcohol intake can be associated with
significant social and physical consequences

–for the development of cirrhosis:
•requirement for 80 grams of ethanol daily for 10 to 20
Alcohol and the liver

•In 2009, WHO listed alcohol use as one of the
leading causes of the global burden of
disease and injury, surpassed only slightly by
childhood malnourishment and unsafe sex.


•This placed alcohol use ahead of unsafe water
and sanitation, hypertension, high cholesterol,
and tobacco use, and clearly affirms that
alcohol is the most widely abused substance
Loading…
Alcoholism and the Effects of
Alcohol

•In the United States, approximately 100 000
deaths per year are attributed to alcohol abuse.

•Alcohol use is an underlying cause of more
than 30 conditions and a definite contributing
factor to many more, including
–psychotic disorder
–alcoholic cardiomyopathy
–amnesic syndrome
–alcoholic liver disease.
Alcoholism and the Effects of
Alcohol

•The Mayo Clinic defined alcoholism as a
chronic disease in which the body becomes
reliant upon alcohol (ethanol).

•Furthermore, it has been referred to as a
syndrome that consists of 2 phases:
–problem drinking
and
–alcohol addiction.

Alcoholic Liver Disease
•Beverage Alcohol

–Beer 5%

–Wine 12%

–Hard Liquor 40%
(Brandy, wisky, Rum)

–Arrack 40 – 50%
Alcoholism and the Effects of
Alcohol
•A standard alcoholic beverage has been described as any drink that
contains 14 g of pure alcohol.
•Irrespective of what form of alcohol is consumed, the greatest risk
factor appears to be the quantity of alcohol consumed.
•The definition for low-risk drinking for men and women differs,
because
–women suffer from hepatic damage and cirrhosis with considerably smaller
amounts of alcohol consumption.
–A man should not drink more than 4 drinks per day and no more than 14 drinks
per week.
–A woman should not drink more than 3 drinks per day and no more than 7 drinks
per week.
Risk for the development of ALD
Time to develop ALD = to amount of alcohol
consumed

•Men: 60-80 gm/day for 10 years

•Women: 20-40 gm/day for 10 years


Alcoholic cirrhosis, develops ONLY in 10 to 20% of
those who are chronically heavy drinkers.
Loading…
Risk for the development of ALD
•Epidemiology

–Over 90% of chronic heavy drinkers will develop
steatosis

–10 to 20% will develop alcoholic hepatitis

–ALD cause death of 1 in 50 people in Scotland

–4 fold increase in deaths from ALD in past 30
years
Risk for the development of ALD
•Risk of liver disease
–Amount of alcohol consumed
–Genetic factors
–Female sex
–Obesity
–Chronic viral hepatitis
–Nutritional impairment
–drugs
Alcohol Metabolism and the Liver
•The liver is the principal organ for alcohol metabolism.
•The body naturally recognizes ethanol alcohol as a foreign, toxic
agent that can disrupt normal homeostasis.
•When we consume ethanol, it is rapidly absorbed by the upper
gastrointestinal tract.
•Ethanol is
–diffused throughout the body, but exposure is greatest to the liver, via the
main portal vein.
–metabolized by the body in the gastric mucosa and the liver. These organs
manage an enzyme referred to as alcohol dehydrogenase, which is used by
the body to oxidize ethanol and convert it into acetaldehyde and other
metabolites.
–Acetaldehyde ultimately is converted by the body into acetic acid, and then
acetate. Acetaldehyde affects protein synthesis.
Alcohol Metabolism and the Liver


•Alcohol’s metabolites, especially acetaldehyde, damage vital liver
cells because of the excessive generation of free radicals.


•Excessive amount of this type of free radical causes oxidative
stress, which results in the body’s inability to prevent and repair
hepatic damage and the destruction of deoxyribonucleic acid.
Alcohol Metabolism and the Liver
•In addition to the immediate damage of acetaldehyde and the free
radicals, the phagocytic cells of the liver, the Kupffer cells, also
mount an immune response.
•This response is the result of an increase in toxins in the blood that
leak from the intestinal wall and enter the blood stream because of
alcohol consumption.
•The activation of Kupffer cells is responsible for early ethanol-
induced liver injury that ultimately leads to the death of
hepatocytes.
•This damage results in the manifestation of alcoholic liver disease,
and eventually to the development of fibrosis, or scar tissue, within
the liver.

Alcohol Metabolism and the Liver
•Alcohol metabolism differs dramatically between sexes.
–Women are much more likely to suffer from liver damage than men as a
result of alcohol consumption. However, this phenomenon is not clearly
understood.

•In addition to sex, the incidence of liver damage depends on the
– individual’s ethnicity
–genetic predisposition
–nutritional state.
Alcohol and the Liver
•Physical examination :

–vary from normal to evidence of cirrhosis or
hepatic decompensation
•Abdominal wall collaterals (caput medusa),
•Ascites,
•Cutaneous telangiectasias,
•Digital clubbing,
•Dupuytren's contractures,
•Gynecomastia,
•Jaundice,
•Malnutrition ,
•Palmar erythema,
•Peripheral neuropathy,
Alcohol and the Liver
•Laboratory findings:

–serum AST (SGOT), ALT (SGPT), and
gammaglutamyl transferase (GGT) are often
abnormal in alcoholic liver disease

–disproportionate elevation of serum AST (SGOT)
compared to ALT (SGPT) ratio is usually greater
than 2.0

–absolute values of serum AST and ALT are almost
always less than 500 IU/L
Alcohol and the Liver

–Consumption of alcohol can lead to a variety of
histopathologic changes in the liver ranging from
steatosis to cirrhosis
• Steatosis,
•alcoholic hepatitis,
•cirrhosis

–The mechanism behind the development of ALD is not
completely understood, because it is estimated that
only 10% to 20% of alcoholics develop cirrhosis.

Alcoholic Liver Disease
•Signs and symptoms
–Steatosis:
•usually asymptomatic, hepatomegaly

–Alcoholic hepatitis:
•malaise, jaundice, tender hepatomegaly, fever, weight
loss, abdominal discomfort

–Cirrhosis:
•similar to other causes of cirrhosis.
•Hepatomegaly, splenomegaly, malaise, jaundice, weight
loss, ascites, signs of CLD
Alcoholic Liver Disease and
Alcoholic Cirrhosis
•Hepatic steatosis;

–commonly referred to as fatty liver, is a frequent diagnosis that is not
exclusive to patients suffering from ALD.

–Fatty liver is the accumulation of triglycerides in the hepatocytes.

–Fatty liver has been demonstrated in 90% to 100% of all heavy drinkers.

–Short-term exposure to 80 g of alcohol (about 8 beers) over several days can
produce hepatic changes consistent with fatty liver disease.

–Fatty liver may develop after a single large binge and does not predict progression to
hepatitis
Alcohol and the Liver
•ALCOHOLIC FATTY LIVER:
–Fatty liver disease can be reversed if alcohol
consumption is stopped or significantly reduced.
–progression to fibrosis or cirrhosis occurred only in
patients who continued to ingest alcohol

–there are often no clinical symptoms, so fatty
liver may be undiagnosed. The only
complaint may be mild tender
hepatomegaly.

Alcohol and the Liver
•ALCOHOLIC FATTY LIVER:
•Pathology:
– macrovesicular fatty infiltration
–inflammatory changes are minimal
–fatty liver is not pathognomonic of ethanol ingestion:
• starvation,
•fatty liver of pregnancy,
•drug toxicity (valproic acid, tetracycline,
•antiviral agents such as zidovudine and dideoxyinosine),
•nonalcoholic steatohepatitis,
•viral hepatitis, particularly hepatitis C virus,
•Reye's syndrome,
•inborn errors of metabolism (such as defects in mitochondrial beta
oxidation)
Alcoholic Liver Disease and
Alcoholic Cirrhosis
•Alcoholic hepatitis
–fatty liver with the development of hepatitis, referred to as steatohepatitis, has
been acknowledged as a precursor for the development of cirrhosis.

–Alcoholic hepatitis results directly from alcohol abuse and is observed in as
many as 35% of heavy drinkers.

–Like other forms of hepatitis, alcoholic hepatitis can be subclinical.

–Laboratory findings are more predictive if the disease has progressed.

–Approximately 40% of patients with alcoholic hepatitis who continue to
drink will develop alcoholic cirrhosis within 1 to 2 years.
Alcohol and the Liver

•ALCOHOLIC HEPATITIS:

14. Alcohol and the Liver

Alcohol and the Liver
• There is a broad spectrum of clinical and
laboratory findings in patients with alcoholic
liver disease, ranging from asymptomatic
fatty liver to alcoholic hepatitis to end-stage
liver failure with jaundice, coagulopathy, and
encephalopathy
Loading…
Alcohol and the Liver
• FINDINGS IN ALCOHOLIC LIVER
DISEASE

–moderate alcohol intake appears to have
cardiovascular benefits

– excessive alcohol intake can be associated with
significant social and physical consequences

–for the development of cirrhosis:
•requirement for 80 grams of ethanol daily for 10 to 20
Alcohol and the liver

•In 2009, WHO listed alcohol use as one of the
leading causes of the global burden of
disease and injury, surpassed only slightly by
childhood malnourishment and unsafe sex.


•This placed alcohol use ahead of unsafe water
and sanitation, hypertension, high cholesterol,
and tobacco use, and clearly affirms that
alcohol is the most widely abused substance
Loading…
Alcoholism and the Effects of
Alcohol

•In the United States, approximately 100 000
deaths per year are attributed to alcohol abuse.

•Alcohol use is an underlying cause of more
than 30 conditions and a definite contributing
factor to many more, including
–psychotic disorder
–alcoholic cardiomyopathy
–amnesic syndrome
–alcoholic liver disease.
Alcoholism and the Effects of
Alcohol

•The Mayo Clinic defined alcoholism as a
chronic disease in which the body becomes
reliant upon alcohol (ethanol).

•Furthermore, it has been referred to as a
syndrome that consists of 2 phases:
–problem drinking
and
–alcohol addiction.

Alcoholic Liver Disease
•Beverage Alcohol

–Beer 5%

–Wine 12%

–Hard Liquor 40%
(Brandy, wisky, Rum)

–Arrack 40 – 50%
Alcoholism and the Effects of
Alcohol
•A standard alcoholic beverage has been described as any drink that
contains 14 g of pure alcohol.
•Irrespective of what form of alcohol is consumed, the greatest risk
factor appears to be the quantity of alcohol consumed.
•The definition for low-risk drinking for men and women differs,
because
–women suffer from hepatic damage and cirrhosis with considerably smaller
amounts of alcohol consumption.
–A man should not drink more than 4 drinks per day and no more than 14 drinks
per week.
–A woman should not drink more than 3 drinks per day and no more than 7 drinks
per week.
Risk for the development of ALD
Time to develop ALD = to amount of alcohol
consumed

•Men: 60-80 gm/day for 10 years

•Women: 20-40 gm/day for 10 years


Alcoholic cirrhosis, develops ONLY in 10 to 20% of
those who are chronically heavy drinkers.
Loading…
Risk for the development of ALD
•Epidemiology

–Over 90% of chronic heavy drinkers will develop
steatosis

–10 to 20% will develop alcoholic hepatitis

–ALD cause death of 1 in 50 people in Scotland

–4 fold increase in deaths from ALD in past 30
years
Risk for the development of ALD
•Risk of liver disease
–Amount of alcohol consumed
–Genetic factors
–Female sex
–Obesity
–Chronic viral hepatitis
–Nutritional impairment
–drugs
Alcohol Metabolism and the Liver
•The liver is the principal organ for alcohol metabolism.
•The body naturally recognizes ethanol alcohol as a foreign, toxic
agent that can disrupt normal homeostasis.
•When we consume ethanol, it is rapidly absorbed by the upper
gastrointestinal tract.
•Ethanol is
–diffused throughout the body, but exposure is greatest to the liver, via the
main portal vein.
–metabolized by the body in the gastric mucosa and the liver. These organs
manage an enzyme referred to as alcohol dehydrogenase, which is used by
the body to oxidize ethanol and convert it into acetaldehyde and other
metabolites.
–Acetaldehyde ultimately is converted by the body into acetic acid, and then
acetate. Acetaldehyde affects protein synthesis.
Alcohol Metabolism and the Liver


•Alcohol’s metabolites, especially acetaldehyde, damage vital liver
cells because of the excessive generation of free radicals.


•Excessive amount of this type of free radical causes oxidative
stress, which results in the body’s inability to prevent and repair
hepatic damage and the destruction of deoxyribonucleic acid.
Alcohol Metabolism and the Liver
•In addition to the immediate damage of acetaldehyde and the free
radicals, the phagocytic cells of the liver, the Kupffer cells, also
mount an immune response.
•This response is the result of an increase in toxins in the blood that
leak from the intestinal wall and enter the blood stream because of
alcohol consumption.
•The activation of Kupffer cells is responsible for early ethanol-
induced liver injury that ultimately leads to the death of
hepatocytes.
•This damage results in the manifestation of alcoholic liver disease,
and eventually to the development of fibrosis, or scar tissue, within
the liver.

Alcohol Metabolism and the Liver
•Alcohol metabolism differs dramatically between sexes.
–Women are much more likely to suffer from liver damage than men as a
result of alcohol consumption. However, this phenomenon is not clearly
understood.

•In addition to sex, the incidence of liver damage depends on the
– individual’s ethnicity
–genetic predisposition
–nutritional state.
Alcohol and the Liver
•Physical examination :

–vary from normal to evidence of cirrhosis or
hepatic decompensation
•Abdominal wall collaterals (caput medusa),
•Ascites,
•Cutaneous telangiectasias,
•Digital clubbing,
•Dupuytren's contractures,
•Gynecomastia,
•Jaundice,
•Malnutrition ,
•Palmar erythema,
•Peripheral neuropathy,
Alcohol and the Liver
•Laboratory findings:

–serum AST (SGOT), ALT (SGPT), and
gammaglutamyl transferase (GGT) are often
abnormal in alcoholic liver disease

–disproportionate elevation of serum AST (SGOT)
compared to ALT (SGPT) ratio is usually greater
than 2.0

–absolute values of serum AST and ALT are almost
always less than 500 IU/L
Alcohol and the Liver

–Consumption of alcohol can lead to a variety of
histopathologic changes in the liver ranging from
steatosis to cirrhosis
• Steatosis,
•alcoholic hepatitis,
•cirrhosis

–The mechanism behind the development of ALD is not
completely understood, because it is estimated that
only 10% to 20% of alcoholics develop cirrhosis.

Alcoholic Liver Disease
•Signs and symptoms
–Steatosis:
•usually asymptomatic, hepatomegaly

–Alcoholic hepatitis:
•malaise, jaundice, tender hepatomegaly, fever, weight
loss, abdominal discomfort

–Cirrhosis:
•similar to other causes of cirrhosis.
•Hepatomegaly, splenomegaly, malaise, jaundice, weight
loss, ascites, signs of CLD
Alcoholic Liver Disease and
Alcoholic Cirrhosis
•Hepatic steatosis;

–commonly referred to as fatty liver, is a frequent diagnosis that is not
exclusive to patients suffering from ALD.

–Fatty liver is the accumulation of triglycerides in the hepatocytes.

–Fatty liver has been demonstrated in 90% to 100% of all heavy drinkers.

–Short-term exposure to 80 g of alcohol (about 8 beers) over several days can
produce hepatic changes consistent with fatty liver disease.

–Fatty liver may develop after a single large binge and does not predict progression to
hepatitis
Alcohol and the Liver
•ALCOHOLIC FATTY LIVER:
–Fatty liver disease can be reversed if alcohol
consumption is stopped or significantly reduced.
–progression to fibrosis or cirrhosis occurred only in
patients who continued to ingest alcohol

–there are often no clinical symptoms, so fatty
liver may be undiagnosed. The only
complaint may be mild tender
hepatomegaly.

Alcohol and the Liver
•ALCOHOLIC FATTY LIVER:
•Pathology:
– macrovesicular fatty infiltration
–inflammatory changes are minimal
–fatty liver is not pathognomonic of ethanol ingestion:
• starvation,
•fatty liver of pregnancy,
•drug toxicity (valproic acid, tetracycline,
•antiviral agents such as zidovudine and dideoxyinosine),
•nonalcoholic steatohepatitis,
•viral hepatitis, particularly hepatitis C virus,
•Reye's syndrome,
•inborn errors of metabolism (such as defects in mitochondrial beta
oxidation)
Alcoholic Liver Disease and
Alcoholic Cirrhosis
•Alcoholic hepatitis
–fatty liver with the development of hepatitis, referred to as steatohepatitis, has
been acknowledged as a precursor for the development of cirrhosis.

–Alcoholic hepatitis results directly from alcohol abuse and is observed in as
many as 35% of heavy drinkers.

–Like other forms of hepatitis, alcoholic hepatitis can be subclinical.

–Laboratory findings are more predictive if the disease has progressed.

–Approximately 40% of patients with alcoholic hepatitis who continue to
drink will develop alcoholic cirrhosis within 1 to 2 years.
Alcohol and the Liver

•ALCOHOLIC HEPATITIS:

15. Alcohol and the Liver

Alcohol and the Liver
• There is a broad spectrum of clinical and
laboratory findings in patients with alcoholic
liver disease, ranging from asymptomatic
fatty liver to alcoholic hepatitis to end-stage
liver failure with jaundice, coagulopathy, and
encephalopathy
Loading…
Alcohol and the Liver
• FINDINGS IN ALCOHOLIC LIVER
DISEASE

–moderate alcohol intake appears to have
cardiovascular benefits

– excessive alcohol intake can be associated with
significant social and physical consequences

–for the development of cirrhosis:
•requirement for 80 grams of ethanol daily for 10 to 20
Alcohol and the liver

•In 2009, WHO listed alcohol use as one of the
leading causes of the global burden of
disease and injury, surpassed only slightly by
childhood malnourishment and unsafe sex.


•This placed alcohol use ahead of unsafe water
and sanitation, hypertension, high cholesterol,
and tobacco use, and clearly affirms that
alcohol is the most widely abused substance
Loading…
Alcoholism and the Effects of
Alcohol

•In the United States, approximately 100 000
deaths per year are attributed to alcohol abuse.

•Alcohol use is an underlying cause of more
than 30 conditions and a definite contributing
factor to many more, including
–psychotic disorder
–alcoholic cardiomyopathy
–amnesic syndrome
–alcoholic liver disease.
Alcoholism and the Effects of
Alcohol

•The Mayo Clinic defined alcoholism as a
chronic disease in which the body becomes
reliant upon alcohol (ethanol).

•Furthermore, it has been referred to as a
syndrome that consists of 2 phases:
–problem drinking
and
–alcohol addiction.

Alcoholic Liver Disease
•Beverage Alcohol

–Beer 5%

–Wine 12%

–Hard Liquor 40%
(Brandy, wisky, Rum)

–Arrack 40 – 50%
Alcoholism and the Effects of
Alcohol
•A standard alcoholic beverage has been described as any drink that
contains 14 g of pure alcohol.
•Irrespective of what form of alcohol is consumed, the greatest risk
factor appears to be the quantity of alcohol consumed.
•The definition for low-risk drinking for men and women differs,
because
–women suffer from hepatic damage and cirrhosis with considerably smaller
amounts of alcohol consumption.
–A man should not drink more than 4 drinks per day and no more than 14 drinks
per week.
–A woman should not drink more than 3 drinks per day and no more than 7 drinks
per week.
Risk for the development of ALD
Time to develop ALD = to amount of alcohol
consumed

•Men: 60-80 gm/day for 10 years

•Women: 20-40 gm/day for 10 years


Alcoholic cirrhosis, develops ONLY in 10 to 20% of
those who are chronically heavy drinkers.
Loading…
Risk for the development of ALD
•Epidemiology

–Over 90% of chronic heavy drinkers will develop
steatosis

–10 to 20% will develop alcoholic hepatitis

–ALD cause death of 1 in 50 people in Scotland

–4 fold increase in deaths from ALD in past 30
years
Risk for the development of ALD
•Risk of liver disease
–Amount of alcohol consumed
–Genetic factors
–Female sex
–Obesity
–Chronic viral hepatitis
–Nutritional impairment
–drugs
Alcohol Metabolism and the Liver
•The liver is the principal organ for alcohol metabolism.
•The body naturally recognizes ethanol alcohol as a foreign, toxic
agent that can disrupt normal homeostasis.
•When we consume ethanol, it is rapidly absorbed by the upper
gastrointestinal tract.
•Ethanol is
–diffused throughout the body, but exposure is greatest to the liver, via the
main portal vein.
–metabolized by the body in the gastric mucosa and the liver. These organs
manage an enzyme referred to as alcohol dehydrogenase, which is used by
the body to oxidize ethanol and convert it into acetaldehyde and other
metabolites.
–Acetaldehyde ultimately is converted by the body into acetic acid, and then
acetate. Acetaldehyde affects protein synthesis.
Alcohol Metabolism and the Liver


•Alcohol’s metabolites, especially acetaldehyde, damage vital liver
cells because of the excessive generation of free radicals.


•Excessive amount of this type of free radical causes oxidative
stress, which results in the body’s inability to prevent and repair
hepatic damage and the destruction of deoxyribonucleic acid.
Alcohol Metabolism and the Liver
•In addition to the immediate damage of acetaldehyde and the free
radicals, the phagocytic cells of the liver, the Kupffer cells, also
mount an immune response.
•This response is the result of an increase in toxins in the blood that
leak from the intestinal wall and enter the blood stream because of
alcohol consumption.
•The activation of Kupffer cells is responsible for early ethanol-
induced liver injury that ultimately leads to the death of
hepatocytes.
•This damage results in the manifestation of alcoholic liver disease,
and eventually to the development of fibrosis, or scar tissue, within
the liver.

Alcohol Metabolism and the Liver
•Alcohol metabolism differs dramatically between sexes.
–Women are much more likely to suffer from liver damage than men as a
result of alcohol consumption. However, this phenomenon is not clearly
understood.

•In addition to sex, the incidence of liver damage depends on the
– individual’s ethnicity
–genetic predisposition
–nutritional state.
Alcohol and the Liver
•Physical examination :

–vary from normal to evidence of cirrhosis or
hepatic decompensation
•Abdominal wall collaterals (caput medusa),
•Ascites,
•Cutaneous telangiectasias,
•Digital clubbing,
•Dupuytren's contractures,
•Gynecomastia,
•Jaundice,
•Malnutrition ,
•Palmar erythema,
•Peripheral neuropathy,
Alcohol and the Liver
•Laboratory findings:

–serum AST (SGOT), ALT (SGPT), and
gammaglutamyl transferase (GGT) are often
abnormal in alcoholic liver disease

–disproportionate elevation of serum AST (SGOT)
compared to ALT (SGPT) ratio is usually greater
than 2.0

–absolute values of serum AST and ALT are almost
always less than 500 IU/L
Alcohol and the Liver

–Consumption of alcohol can lead to a variety of
histopathologic changes in the liver ranging from
steatosis to cirrhosis
• Steatosis,
•alcoholic hepatitis,
•cirrhosis

–The mechanism behind the development of ALD is not
completely understood, because it is estimated that
only 10% to 20% of alcoholics develop cirrhosis.

Alcoholic Liver Disease
•Signs and symptoms
–Steatosis:
•usually asymptomatic, hepatomegaly

–Alcoholic hepatitis:
•malaise, jaundice, tender hepatomegaly, fever, weight
loss, abdominal discomfort

–Cirrhosis:
•similar to other causes of cirrhosis.
•Hepatomegaly, splenomegaly, malaise, jaundice, weight
loss, ascites, signs of CLD
Alcoholic Liver Disease and
Alcoholic Cirrhosis
•Hepatic steatosis;

–commonly referred to as fatty liver, is a frequent diagnosis that is not
exclusive to patients suffering from ALD.

–Fatty liver is the accumulation of triglycerides in the hepatocytes.

–Fatty liver has been demonstrated in 90% to 100% of all heavy drinkers.

–Short-term exposure to 80 g of alcohol (about 8 beers) over several days can
produce hepatic changes consistent with fatty liver disease.

–Fatty liver may develop after a single large binge and does not predict progression to
hepatitis
Alcohol and the Liver
•ALCOHOLIC FATTY LIVER:
–Fatty liver disease can be reversed if alcohol
consumption is stopped or significantly reduced.
–progression to fibrosis or cirrhosis occurred only in
patients who continued to ingest alcohol

–there are often no clinical symptoms, so fatty
liver may be undiagnosed. The only
complaint may be mild tender
hepatomegaly.

Alcohol and the Liver
•ALCOHOLIC FATTY LIVER:
•Pathology:
– macrovesicular fatty infiltration
–inflammatory changes are minimal
–fatty liver is not pathognomonic of ethanol ingestion:
• starvation,
•fatty liver of pregnancy,
•drug toxicity (valproic acid, tetracycline,
•antiviral agents such as zidovudine and dideoxyinosine),
•nonalcoholic steatohepatitis,
•viral hepatitis, particularly hepatitis C virus,
•Reye's syndrome,
•inborn errors of metabolism (such as defects in mitochondrial beta
oxidation)
Alcoholic Liver Disease and
Alcoholic Cirrhosis
•Alcoholic hepatitis
–fatty liver with the development of hepatitis, referred to as steatohepatitis, has
been acknowledged as a precursor for the development of cirrhosis.

–Alcoholic hepatitis results directly from alcohol abuse and is observed in as
many as 35% of heavy drinkers.

–Like other forms of hepatitis, alcoholic hepatitis can be subclinical.

–Laboratory findings are more predictive if the disease has progressed.

–Approximately 40% of patients with alcoholic hepatitis who continue to
drink will develop alcoholic cirrhosis within 1 to 2 years.
Alcohol and the Liver

•ALCOHOLIC HEPATITIS:

16. Alcohol and the Liver

Alcohol and the Liver
• There is a broad spectrum of clinical and
laboratory findings in patients with alcoholic
liver disease, ranging from asymptomatic
fatty liver to alcoholic hepatitis to end-stage
liver failure with jaundice, coagulopathy, and
encephalopathy
Loading…
Alcohol and the Liver
• FINDINGS IN ALCOHOLIC LIVER
DISEASE

–moderate alcohol intake appears to have
cardiovascular benefits

– excessive alcohol intake can be associated with
significant social and physical consequences

–for the development of cirrhosis:
•requirement for 80 grams of ethanol daily for 10 to 20
Alcohol and the liver

•In 2009, WHO listed alcohol use as one of the
leading causes of the global burden of
disease and injury, surpassed only slightly by
childhood malnourishment and unsafe sex.


•This placed alcohol use ahead of unsafe water
and sanitation, hypertension, high cholesterol,
and tobacco use, and clearly affirms that
alcohol is the most widely abused substance
Loading…
Alcoholism and the Effects of
Alcohol

•In the United States, approximately 100 000
deaths per year are attributed to alcohol abuse.

•Alcohol use is an underlying cause of more
than 30 conditions and a definite contributing
factor to many more, including
–psychotic disorder
–alcoholic cardiomyopathy
–amnesic syndrome
–alcoholic liver disease.
Alcoholism and the Effects of
Alcohol

•The Mayo Clinic defined alcoholism as a
chronic disease in which the body becomes
reliant upon alcohol (ethanol).

•Furthermore, it has been referred to as a
syndrome that consists of 2 phases:
–problem drinking
and
–alcohol addiction.

Alcoholic Liver Disease
•Beverage Alcohol

–Beer 5%

–Wine 12%

–Hard Liquor 40%
(Brandy, wisky, Rum)

–Arrack 40 – 50%
Alcoholism and the Effects of
Alcohol
•A standard alcoholic beverage has been described as any drink that
contains 14 g of pure alcohol.
•Irrespective of what form of alcohol is consumed, the greatest risk
factor appears to be the quantity of alcohol consumed.
•The definition for low-risk drinking for men and women differs,
because
–women suffer from hepatic damage and cirrhosis with considerably smaller
amounts of alcohol consumption.
–A man should not drink more than 4 drinks per day and no more than 14 drinks
per week.
–A woman should not drink more than 3 drinks per day and no more than 7 drinks
per week.
Risk for the development of ALD
Time to develop ALD = to amount of alcohol
consumed

•Men: 60-80 gm/day for 10 years

•Women: 20-40 gm/day for 10 years


Alcoholic cirrhosis, develops ONLY in 10 to 20% of
those who are chronically heavy drinkers.
Loading…
Risk for the development of ALD
•Epidemiology

–Over 90% of chronic heavy drinkers will develop
steatosis

–10 to 20% will develop alcoholic hepatitis

–ALD cause death of 1 in 50 people in Scotland

–4 fold increase in deaths from ALD in past 30
years
Risk for the development of ALD
•Risk of liver disease
–Amount of alcohol consumed
–Genetic factors
–Female sex
–Obesity
–Chronic viral hepatitis
–Nutritional impairment
–drugs
Alcohol Metabolism and the Liver
•The liver is the principal organ for alcohol metabolism.
•The body naturally recognizes ethanol alcohol as a foreign, toxic
agent that can disrupt normal homeostasis.
•When we consume ethanol, it is rapidly absorbed by the upper
gastrointestinal tract.
•Ethanol is
–diffused throughout the body, but exposure is greatest to the liver, via the
main portal vein.
–metabolized by the body in the gastric mucosa and the liver. These organs
manage an enzyme referred to as alcohol dehydrogenase, which is used by
the body to oxidize ethanol and convert it into acetaldehyde and other
metabolites.
–Acetaldehyde ultimately is converted by the body into acetic acid, and then
acetate. Acetaldehyde affects protein synthesis.
Alcohol Metabolism and the Liver


•Alcohol’s metabolites, especially acetaldehyde, damage vital liver
cells because of the excessive generation of free radicals.


•Excessive amount of this type of free radical causes oxidative
stress, which results in the body’s inability to prevent and repair
hepatic damage and the destruction of deoxyribonucleic acid.
Alcohol Metabolism and the Liver
•In addition to the immediate damage of acetaldehyde and the free
radicals, the phagocytic cells of the liver, the Kupffer cells, also
mount an immune response.
•This response is the result of an increase in toxins in the blood that
leak from the intestinal wall and enter the blood stream because of
alcohol consumption.
•The activation of Kupffer cells is responsible for early ethanol-
induced liver injury that ultimately leads to the death of
hepatocytes.
•This damage results in the manifestation of alcoholic liver disease,
and eventually to the development of fibrosis, or scar tissue, within
the liver.

Alcohol Metabolism and the Liver
•Alcohol metabolism differs dramatically between sexes.
–Women are much more likely to suffer from liver damage than men as a
result of alcohol consumption. However, this phenomenon is not clearly
understood.

•In addition to sex, the incidence of liver damage depends on the
– individual’s ethnicity
–genetic predisposition
–nutritional state.
Alcohol and the Liver
•Physical examination :

–vary from normal to evidence of cirrhosis or
hepatic decompensation
•Abdominal wall collaterals (caput medusa),
•Ascites,
•Cutaneous telangiectasias,
•Digital clubbing,
•Dupuytren's contractures,
•Gynecomastia,
•Jaundice,
•Malnutrition ,
•Palmar erythema,
•Peripheral neuropathy,
Alcohol and the Liver
•Laboratory findings:

–serum AST (SGOT), ALT (SGPT), and
gammaglutamyl transferase (GGT) are often
abnormal in alcoholic liver disease

–disproportionate elevation of serum AST (SGOT)
compared to ALT (SGPT) ratio is usually greater
than 2.0

–absolute values of serum AST and ALT are almost
always less than 500 IU/L
Alcohol and the Liver

–Consumption of alcohol can lead to a variety of
histopathologic changes in the liver ranging from
steatosis to cirrhosis
• Steatosis,
•alcoholic hepatitis,
•cirrhosis

–The mechanism behind the development of ALD is not
completely understood, because it is estimated that
only 10% to 20% of alcoholics develop cirrhosis.

Alcoholic Liver Disease
•Signs and symptoms
–Steatosis:
•usually asymptomatic, hepatomegaly

–Alcoholic hepatitis:
•malaise, jaundice, tender hepatomegaly, fever, weight
loss, abdominal discomfort

–Cirrhosis:
•similar to other causes of cirrhosis.
•Hepatomegaly, splenomegaly, malaise, jaundice, weight
loss, ascites, signs of CLD
Alcoholic Liver Disease and
Alcoholic Cirrhosis
•Hepatic steatosis;

–commonly referred to as fatty liver, is a frequent diagnosis that is not
exclusive to patients suffering from ALD.

–Fatty liver is the accumulation of triglycerides in the hepatocytes.

–Fatty liver has been demonstrated in 90% to 100% of all heavy drinkers.

–Short-term exposure to 80 g of alcohol (about 8 beers) over several days can
produce hepatic changes consistent with fatty liver disease.

–Fatty liver may develop after a single large binge and does not predict progression to
hepatitis
Alcohol and the Liver
•ALCOHOLIC FATTY LIVER:
–Fatty liver disease can be reversed if alcohol
consumption is stopped or significantly reduced.
–progression to fibrosis or cirrhosis occurred only in
patients who continued to ingest alcohol

–there are often no clinical symptoms, so fatty
liver may be undiagnosed. The only
complaint may be mild tender
hepatomegaly.

Alcohol and the Liver
•ALCOHOLIC FATTY LIVER:
•Pathology:
– macrovesicular fatty infiltration
–inflammatory changes are minimal
–fatty liver is not pathognomonic of ethanol ingestion:
• starvation,
•fatty liver of pregnancy,
•drug toxicity (valproic acid, tetracycline,
•antiviral agents such as zidovudine and dideoxyinosine),
•nonalcoholic steatohepatitis,
•viral hepatitis, particularly hepatitis C virus,
•Reye's syndrome,
•inborn errors of metabolism (such as defects in mitochondrial beta
oxidation)
Alcoholic Liver Disease and
Alcoholic Cirrhosis
•Alcoholic hepatitis
–fatty liver with the development of hepatitis, referred to as steatohepatitis, has
been acknowledged as a precursor for the development of cirrhosis.

–Alcoholic hepatitis results directly from alcohol abuse and is observed in as
many as 35% of heavy drinkers.

–Like other forms of hepatitis, alcoholic hepatitis can be subclinical.

–Laboratory findings are more predictive if the disease has progressed.

–Approximately 40% of patients with alcoholic hepatitis who continue to
drink will develop alcoholic cirrhosis within 1 to 2 years.
Alcohol and the Liver

•ALCOHOLIC HEPATITIS:

17. Alcohol and the Liver

Alcohol and the Liver
• There is a broad spectrum of clinical and
laboratory findings in patients with alcoholic
liver disease, ranging from asymptomatic
fatty liver to alcoholic hepatitis to end-stage
liver failure with jaundice, coagulopathy, and
encephalopathy
Loading…
Alcohol and the Liver
• FINDINGS IN ALCOHOLIC LIVER
DISEASE

–moderate alcohol intake appears to have
cardiovascular benefits

– excessive alcohol intake can be associated with
significant social and physical consequences

–for the development of cirrhosis:
•requirement for 80 grams of ethanol daily for 10 to 20
Alcohol and the liver

•In 2009, WHO listed alcohol use as one of the
leading causes of the global burden of
disease and injury, surpassed only slightly by
childhood malnourishment and unsafe sex.


•This placed alcohol use ahead of unsafe water
and sanitation, hypertension, high cholesterol,
and tobacco use, and clearly affirms that
alcohol is the most widely abused substance
Loading…
Alcoholism and the Effects of
Alcohol

•In the United States, approximately 100 000
deaths per year are attributed to alcohol abuse.

•Alcohol use is an underlying cause of more
than 30 conditions and a definite contributing
factor to many more, including
–psychotic disorder
–alcoholic cardiomyopathy
–amnesic syndrome
–alcoholic liver disease.
Alcoholism and the Effects of
Alcohol

•The Mayo Clinic defined alcoholism as a
chronic disease in which the body becomes
reliant upon alcohol (ethanol).

•Furthermore, it has been referred to as a
syndrome that consists of 2 phases:
–problem drinking
and
–alcohol addiction.

Alcoholic Liver Disease
•Beverage Alcohol

–Beer 5%

–Wine 12%

–Hard Liquor 40%
(Brandy, wisky, Rum)

–Arrack 40 – 50%
Alcoholism and the Effects of
Alcohol
•A standard alcoholic beverage has been described as any drink that
contains 14 g of pure alcohol.
•Irrespective of what form of alcohol is consumed, the greatest risk
factor appears to be the quantity of alcohol consumed.
•The definition for low-risk drinking for men and women differs,
because
–women suffer from hepatic damage and cirrhosis with considerably smaller
amounts of alcohol consumption.
–A man should not drink more than 4 drinks per day and no more than 14 drinks
per week.
–A woman should not drink more than 3 drinks per day and no more than 7 drinks
per week.
Risk for the development of ALD
Time to develop ALD = to amount of alcohol
consumed

•Men: 60-80 gm/day for 10 years

•Women: 20-40 gm/day for 10 years


Alcoholic cirrhosis, develops ONLY in 10 to 20% of
those who are chronically heavy drinkers.
Loading…
Risk for the development of ALD
•Epidemiology

–Over 90% of chronic heavy drinkers will develop
steatosis

–10 to 20% will develop alcoholic hepatitis

–ALD cause death of 1 in 50 people in Scotland

–4 fold increase in deaths from ALD in past 30
years
Risk for the development of ALD
•Risk of liver disease
–Amount of alcohol consumed
–Genetic factors
–Female sex
–Obesity
–Chronic viral hepatitis
–Nutritional impairment
–drugs
Alcohol Metabolism and the Liver
•The liver is the principal organ for alcohol metabolism.
•The body naturally recognizes ethanol alcohol as a foreign, toxic
agent that can disrupt normal homeostasis.
•When we consume ethanol, it is rapidly absorbed by the upper
gastrointestinal tract.
•Ethanol is
–diffused throughout the body, but exposure is greatest to the liver, via the
main portal vein.
–metabolized by the body in the gastric mucosa and the liver. These organs
manage an enzyme referred to as alcohol dehydrogenase, which is used by
the body to oxidize ethanol and convert it into acetaldehyde and other
metabolites.
–Acetaldehyde ultimately is converted by the body into acetic acid, and then
acetate. Acetaldehyde affects protein synthesis.
Alcohol Metabolism and the Liver


•Alcohol’s metabolites, especially acetaldehyde, damage vital liver
cells because of the excessive generation of free radicals.


•Excessive amount of this type of free radical causes oxidative
stress, which results in the body’s inability to prevent and repair
hepatic damage and the destruction of deoxyribonucleic acid.
Alcohol Metabolism and the Liver
•In addition to the immediate damage of acetaldehyde and the free
radicals, the phagocytic cells of the liver, the Kupffer cells, also
mount an immune response.
•This response is the result of an increase in toxins in the blood that
leak from the intestinal wall and enter the blood stream because of
alcohol consumption.
•The activation of Kupffer cells is responsible for early ethanol-
induced liver injury that ultimately leads to the death of
hepatocytes.
•This damage results in the manifestation of alcoholic liver disease,
and eventually to the development of fibrosis, or scar tissue, within
the liver.

Alcohol Metabolism and the Liver
•Alcohol metabolism differs dramatically between sexes.
–Women are much more likely to suffer from liver damage than men as a
result of alcohol consumption. However, this phenomenon is not clearly
understood.

•In addition to sex, the incidence of liver damage depends on the
– individual’s ethnicity
–genetic predisposition
–nutritional state.
Alcohol and the Liver
•Physical examination :

–vary from normal to evidence of cirrhosis or
hepatic decompensation
•Abdominal wall collaterals (caput medusa),
•Ascites,
•Cutaneous telangiectasias,
•Digital clubbing,
•Dupuytren's contractures,
•Gynecomastia,
•Jaundice,
•Malnutrition ,
•Palmar erythema,
•Peripheral neuropathy,
Alcohol and the Liver
•Laboratory findings:

–serum AST (SGOT), ALT (SGPT), and
gammaglutamyl transferase (GGT) are often
abnormal in alcoholic liver disease

–disproportionate elevation of serum AST (SGOT)
compared to ALT (SGPT) ratio is usually greater
than 2.0

–absolute values of serum AST and ALT are almost
always less than 500 IU/L
Alcohol and the Liver

–Consumption of alcohol can lead to a variety of
histopathologic changes in the liver ranging from
steatosis to cirrhosis
• Steatosis,
•alcoholic hepatitis,
•cirrhosis

–The mechanism behind the development of ALD is not
completely understood, because it is estimated that
only 10% to 20% of alcoholics develop cirrhosis.

Alcoholic Liver Disease
•Signs and symptoms
–Steatosis:
•usually asymptomatic, hepatomegaly

–Alcoholic hepatitis:
•malaise, jaundice, tender hepatomegaly, fever, weight
loss, abdominal discomfort

–Cirrhosis:
•similar to other causes of cirrhosis.
•Hepatomegaly, splenomegaly, malaise, jaundice, weight
loss, ascites, signs of CLD
Alcoholic Liver Disease and
Alcoholic Cirrhosis
•Hepatic steatosis;

–commonly referred to as fatty liver, is a frequent diagnosis that is not
exclusive to patients suffering from ALD.

–Fatty liver is the accumulation of triglycerides in the hepatocytes.

–Fatty liver has been demonstrated in 90% to 100% of all heavy drinkers.

–Short-term exposure to 80 g of alcohol (about 8 beers) over several days can
produce hepatic changes consistent with fatty liver disease.

–Fatty liver may develop after a single large binge and does not predict progression to
hepatitis
Alcohol and the Liver
•ALCOHOLIC FATTY LIVER:
–Fatty liver disease can be reversed if alcohol
consumption is stopped or significantly reduced.
–progression to fibrosis or cirrhosis occurred only in
patients who continued to ingest alcohol

–there are often no clinical symptoms, so fatty
liver may be undiagnosed. The only
complaint may be mild tender
hepatomegaly.

Alcohol and the Liver
•ALCOHOLIC FATTY LIVER:
•Pathology:
– macrovesicular fatty infiltration
–inflammatory changes are minimal
–fatty liver is not pathognomonic of ethanol ingestion:
• starvation,
•fatty liver of pregnancy,
•drug toxicity (valproic acid, tetracycline,
•antiviral agents such as zidovudine and dideoxyinosine),
•nonalcoholic steatohepatitis,
•viral hepatitis, particularly hepatitis C virus,
•Reye's syndrome,
•inborn errors of metabolism (such as defects in mitochondrial beta
oxidation)
Alcoholic Liver Disease and
Alcoholic Cirrhosis
•Alcoholic hepatitis
–fatty liver with the development of hepatitis, referred to as steatohepatitis, has
been acknowledged as a precursor for the development of cirrhosis.

–Alcoholic hepatitis results directly from alcohol abuse and is observed in as
many as 35% of heavy drinkers.

–Like other forms of hepatitis, alcoholic hepatitis can be subclinical.

–Laboratory findings are more predictive if the disease has progressed.

–Approximately 40% of patients with alcoholic hepatitis who continue to
drink will develop alcoholic cirrhosis within 1 to 2 years.
Alcohol and the Liver

•ALCOHOLIC HEPATITIS:

18. Alcohol and the Liver

Alcohol and the Liver
• There is a broad spectrum of clinical and
laboratory findings in patients with alcoholic
liver disease, ranging from asymptomatic
fatty liver to alcoholic hepatitis to end-stage
liver failure with jaundice, coagulopathy, and
encephalopathy
Loading…
Alcohol and the Liver
• FINDINGS IN ALCOHOLIC LIVER
DISEASE

–moderate alcohol intake appears to have
cardiovascular benefits

– excessive alcohol intake can be associated with
significant social and physical consequences

–for the development of cirrhosis:
•requirement for 80 grams of ethanol daily for 10 to 20
Alcohol and the liver

•In 2009, WHO listed alcohol use as one of the
leading causes of the global burden of
disease and injury, surpassed only slightly by
childhood malnourishment and unsafe sex.


•This placed alcohol use ahead of unsafe water
and sanitation, hypertension, high cholesterol,
and tobacco use, and clearly affirms that
alcohol is the most widely abused substance
Loading…
Alcoholism and the Effects of
Alcohol

•In the United States, approximately 100 000
deaths per year are attributed to alcohol abuse.

•Alcohol use is an underlying cause of more
than 30 conditions and a definite contributing
factor to many more, including
–psychotic disorder
–alcoholic cardiomyopathy
–amnesic syndrome
–alcoholic liver disease.
Alcoholism and the Effects of
Alcohol

•The Mayo Clinic defined alcoholism as a
chronic disease in which the body becomes
reliant upon alcohol (ethanol).

•Furthermore, it has been referred to as a
syndrome that consists of 2 phases:
–problem drinking
and
–alcohol addiction.

Alcoholic Liver Disease
•Beverage Alcohol

–Beer 5%

–Wine 12%

–Hard Liquor 40%
(Brandy, wisky, Rum)

–Arrack 40 – 50%
Alcoholism and the Effects of
Alcohol
•A standard alcoholic beverage has been described as any drink that
contains 14 g of pure alcohol.
•Irrespective of what form of alcohol is consumed, the greatest risk
factor appears to be the quantity of alcohol consumed.
•The definition for low-risk drinking for men and women differs,
because
–women suffer from hepatic damage and cirrhosis with considerably smaller
amounts of alcohol consumption.
–A man should not drink more than 4 drinks per day and no more than 14 drinks
per week.
–A woman should not drink more than 3 drinks per day and no more than 7 drinks
per week.
Risk for the development of ALD
Time to develop ALD = to amount of alcohol
consumed

•Men: 60-80 gm/day for 10 years

•Women: 20-40 gm/day for 10 years


Alcoholic cirrhosis, develops ONLY in 10 to 20% of
those who are chronically heavy drinkers.
Loading…
Risk for the development of ALD
•Epidemiology

–Over 90% of chronic heavy drinkers will develop
steatosis

–10 to 20% will develop alcoholic hepatitis

–ALD cause death of 1 in 50 people in Scotland

–4 fold increase in deaths from ALD in past 30
years
Risk for the development of ALD
•Risk of liver disease
–Amount of alcohol consumed
–Genetic factors
–Female sex
–Obesity
–Chronic viral hepatitis
–Nutritional impairment
–drugs
Alcohol Metabolism and the Liver
•The liver is the principal organ for alcohol metabolism.
•The body naturally recognizes ethanol alcohol as a foreign, toxic
agent that can disrupt normal homeostasis.
•When we consume ethanol, it is rapidly absorbed by the upper
gastrointestinal tract.
•Ethanol is
–diffused throughout the body, but exposure is greatest to the liver, via the
main portal vein.
–metabolized by the body in the gastric mucosa and the liver. These organs
manage an enzyme referred to as alcohol dehydrogenase, which is used by
the body to oxidize ethanol and convert it into acetaldehyde and other
metabolites.
–Acetaldehyde ultimately is converted by the body into acetic acid, and then
acetate. Acetaldehyde affects protein synthesis.
Alcohol Metabolism and the Liver


•Alcohol’s metabolites, especially acetaldehyde, damage vital liver
cells because of the excessive generation of free radicals.


•Excessive amount of this type of free radical causes oxidative
stress, which results in the body’s inability to prevent and repair
hepatic damage and the destruction of deoxyribonucleic acid.
Alcohol Metabolism and the Liver
•In addition to the immediate damage of acetaldehyde and the free
radicals, the phagocytic cells of the liver, the Kupffer cells, also
mount an immune response.
•This response is the result of an increase in toxins in the blood that
leak from the intestinal wall and enter the blood stream because of
alcohol consumption.
•The activation of Kupffer cells is responsible for early ethanol-
induced liver injury that ultimately leads to the death of
hepatocytes.
•This damage results in the manifestation of alcoholic liver disease,
and eventually to the development of fibrosis, or scar tissue, within
the liver.

Alcohol Metabolism and the Liver
•Alcohol metabolism differs dramatically between sexes.
–Women are much more likely to suffer from liver damage than men as a
result of alcohol consumption. However, this phenomenon is not clearly
understood.

•In addition to sex, the incidence of liver damage depends on the
– individual’s ethnicity
–genetic predisposition
–nutritional state.
Alcohol and the Liver
•Physical examination :

–vary from normal to evidence of cirrhosis or
hepatic decompensation
•Abdominal wall collaterals (caput medusa),
•Ascites,
•Cutaneous telangiectasias,
•Digital clubbing,
•Dupuytren's contractures,
•Gynecomastia,
•Jaundice,
•Malnutrition ,
•Palmar erythema,
•Peripheral neuropathy,
Alcohol and the Liver
•Laboratory findings:

–serum AST (SGOT), ALT (SGPT), and
gammaglutamyl transferase (GGT) are often
abnormal in alcoholic liver disease

–disproportionate elevation of serum AST (SGOT)
compared to ALT (SGPT) ratio is usually greater
than 2.0

–absolute values of serum AST and ALT are almost
always less than 500 IU/L
Alcohol and the Liver

–Consumption of alcohol can lead to a variety of
histopathologic changes in the liver ranging from
steatosis to cirrhosis
• Steatosis,
•alcoholic hepatitis,
•cirrhosis

–The mechanism behind the development of ALD is not
completely understood, because it is estimated that
only 10% to 20% of alcoholics develop cirrhosis.

Alcoholic Liver Disease
•Signs and symptoms
–Steatosis:
•usually asymptomatic, hepatomegaly

–Alcoholic hepatitis:
•malaise, jaundice, tender hepatomegaly, fever, weight
loss, abdominal discomfort

–Cirrhosis:
•similar to other causes of cirrhosis.
•Hepatomegaly, splenomegaly, malaise, jaundice, weight
loss, ascites, signs of CLD
Alcoholic Liver Disease and
Alcoholic Cirrhosis
•Hepatic steatosis;

–commonly referred to as fatty liver, is a frequent diagnosis that is not
exclusive to patients suffering from ALD.

–Fatty liver is the accumulation of triglycerides in the hepatocytes.

–Fatty liver has been demonstrated in 90% to 100% of all heavy drinkers.

–Short-term exposure to 80 g of alcohol (about 8 beers) over several days can
produce hepatic changes consistent with fatty liver disease.

–Fatty liver may develop after a single large binge and does not predict progression to
hepatitis
Alcohol and the Liver
•ALCOHOLIC FATTY LIVER:
–Fatty liver disease can be reversed if alcohol
consumption is stopped or significantly reduced.
–progression to fibrosis or cirrhosis occurred only in
patients who continued to ingest alcohol

–there are often no clinical symptoms, so fatty
liver may be undiagnosed. The only
complaint may be mild tender
hepatomegaly.

Alcohol and the Liver
•ALCOHOLIC FATTY LIVER:
•Pathology:
– macrovesicular fatty infiltration
–inflammatory changes are minimal
–fatty liver is not pathognomonic of ethanol ingestion:
• starvation,
•fatty liver of pregnancy,
•drug toxicity (valproic acid, tetracycline,
•antiviral agents such as zidovudine and dideoxyinosine),
•nonalcoholic steatohepatitis,
•viral hepatitis, particularly hepatitis C virus,
•Reye's syndrome,
•inborn errors of metabolism (such as defects in mitochondrial beta
oxidation)
Alcoholic Liver Disease and
Alcoholic Cirrhosis
•Alcoholic hepatitis
–fatty liver with the development of hepatitis, referred to as steatohepatitis, has
been acknowledged as a precursor for the development of cirrhosis.

–Alcoholic hepatitis results directly from alcohol abuse and is observed in as
many as 35% of heavy drinkers.

–Like other forms of hepatitis, alcoholic hepatitis can be subclinical.

–Laboratory findings are more predictive if the disease has progressed.

–Approximately 40% of patients with alcoholic hepatitis who continue to
drink will develop alcoholic cirrhosis within 1 to 2 years.
Alcohol and the Liver

•ALCOHOLIC HEPATITIS:

19. Alcohol and the Liver

Alcohol and the Liver
• There is a broad spectrum of clinical and
laboratory findings in patients with alcoholic
liver disease, ranging from asymptomatic
fatty liver to alcoholic hepatitis to end-stage
liver failure with jaundice, coagulopathy, and
encephalopathy
Loading…
Alcohol and the Liver
• FINDINGS IN ALCOHOLIC LIVER
DISEASE

–moderate alcohol intake appears to have
cardiovascular benefits

– excessive alcohol intake can be associated with
significant social and physical consequences

–for the development of cirrhosis:
•requirement for 80 grams of ethanol daily for 10 to 20
Alcohol and the liver

•In 2009, WHO listed alcohol use as one of the
leading causes of the global burden of
disease and injury, surpassed only slightly by
childhood malnourishment and unsafe sex.


•This placed alcohol use ahead of unsafe water
and sanitation, hypertension, high cholesterol,
and tobacco use, and clearly affirms that
alcohol is the most widely abused substance
Loading…
Alcoholism and the Effects of
Alcohol

•In the United States, approximately 100 000
deaths per year are attributed to alcohol abuse.

•Alcohol use is an underlying cause of more
than 30 conditions and a definite contributing
factor to many more, including
–psychotic disorder
–alcoholic cardiomyopathy
–amnesic syndrome
–alcoholic liver disease.
Alcoholism and the Effects of
Alcohol

•The Mayo Clinic defined alcoholism as a
chronic disease in which the body becomes
reliant upon alcohol (ethanol).

•Furthermore, it has been referred to as a
syndrome that consists of 2 phases:
–problem drinking
and
–alcohol addiction.

Alcoholic Liver Disease
•Beverage Alcohol

–Beer 5%

–Wine 12%

–Hard Liquor 40%
(Brandy, wisky, Rum)

–Arrack 40 – 50%
Alcoholism and the Effects of
Alcohol
•A standard alcoholic beverage has been described as any drink that
contains 14 g of pure alcohol.
•Irrespective of what form of alcohol is consumed, the greatest risk
factor appears to be the quantity of alcohol consumed.
•The definition for low-risk drinking for men and women differs,
because
–women suffer from hepatic damage and cirrhosis with considerably smaller
amounts of alcohol consumption.
–A man should not drink more than 4 drinks per day and no more than 14 drinks
per week.
–A woman should not drink more than 3 drinks per day and no more than 7 drinks
per week.
Risk for the development of ALD
Time to develop ALD = to amount of alcohol
consumed

•Men: 60-80 gm/day for 10 years

•Women: 20-40 gm/day for 10 years


Alcoholic cirrhosis, develops ONLY in 10 to 20% of
those who are chronically heavy drinkers.
Loading…
Risk for the development of ALD
•Epidemiology

–Over 90% of chronic heavy drinkers will develop
steatosis

–10 to 20% will develop alcoholic hepatitis

–ALD cause death of 1 in 50 people in Scotland

–4 fold increase in deaths from ALD in past 30
years
Risk for the development of ALD
•Risk of liver disease
–Amount of alcohol consumed
–Genetic factors
–Female sex
–Obesity
–Chronic viral hepatitis
–Nutritional impairment
–drugs
Alcohol Metabolism and the Liver
•The liver is the principal organ for alcohol metabolism.
•The body naturally recognizes ethanol alcohol as a foreign, toxic
agent that can disrupt normal homeostasis.
•When we consume ethanol, it is rapidly absorbed by the upper
gastrointestinal tract.
•Ethanol is
–diffused throughout the body, but exposure is greatest to the liver, via the
main portal vein.
–metabolized by the body in the gastric mucosa and the liver. These organs
manage an enzyme referred to as alcohol dehydrogenase, which is used by
the body to oxidize ethanol and convert it into acetaldehyde and other
metabolites.
–Acetaldehyde ultimately is converted by the body into acetic acid, and then
acetate. Acetaldehyde affects protein synthesis.
Alcohol Metabolism and the Liver


•Alcohol’s metabolites, especially acetaldehyde, damage vital liver
cells because of the excessive generation of free radicals.


•Excessive amount of this type of free radical causes oxidative
stress, which results in the body’s inability to prevent and repair
hepatic damage and the destruction of deoxyribonucleic acid.
Alcohol Metabolism and the Liver
•In addition to the immediate damage of acetaldehyde and the free
radicals, the phagocytic cells of the liver, the Kupffer cells, also
mount an immune response.
•This response is the result of an increase in toxins in the blood that
leak from the intestinal wall and enter the blood stream because of
alcohol consumption.
•The activation of Kupffer cells is responsible for early ethanol-
induced liver injury that ultimately leads to the death of
hepatocytes.
•This damage results in the manifestation of alcoholic liver disease,
and eventually to the development of fibrosis, or scar tissue, within
the liver.

Alcohol Metabolism and the Liver
•Alcohol metabolism differs dramatically between sexes.
–Women are much more likely to suffer from liver damage than men as a
result of alcohol consumption. However, this phenomenon is not clearly
understood.

•In addition to sex, the incidence of liver damage depends on the
– individual’s ethnicity
–genetic predisposition
–nutritional state.
Alcohol and the Liver
•Physical examination :

–vary from normal to evidence of cirrhosis or
hepatic decompensation
•Abdominal wall collaterals (caput medusa),
•Ascites,
•Cutaneous telangiectasias,
•Digital clubbing,
•Dupuytren's contractures,
•Gynecomastia,
•Jaundice,
•Malnutrition ,
•Palmar erythema,
•Peripheral neuropathy,
Alcohol and the Liver
•Laboratory findings:

–serum AST (SGOT), ALT (SGPT), and
gammaglutamyl transferase (GGT) are often
abnormal in alcoholic liver disease

–disproportionate elevation of serum AST (SGOT)
compared to ALT (SGPT) ratio is usually greater
than 2.0

–absolute values of serum AST and ALT are almost
always less than 500 IU/L
Alcohol and the Liver

–Consumption of alcohol can lead to a variety of
histopathologic changes in the liver ranging from
steatosis to cirrhosis
• Steatosis,
•alcoholic hepatitis,
•cirrhosis

–The mechanism behind the development of ALD is not
completely understood, because it is estimated that
only 10% to 20% of alcoholics develop cirrhosis.

Alcoholic Liver Disease
•Signs and symptoms
–Steatosis:
•usually asymptomatic, hepatomegaly

–Alcoholic hepatitis:
•malaise, jaundice, tender hepatomegaly, fever, weight
loss, abdominal discomfort

–Cirrhosis:
•similar to other causes of cirrhosis.
•Hepatomegaly, splenomegaly, malaise, jaundice, weight
loss, ascites, signs of CLD
Alcoholic Liver Disease and
Alcoholic Cirrhosis
•Hepatic steatosis;

–commonly referred to as fatty liver, is a frequent diagnosis that is not
exclusive to patients suffering from ALD.

–Fatty liver is the accumulation of triglycerides in the hepatocytes.

–Fatty liver has been demonstrated in 90% to 100% of all heavy drinkers.

–Short-term exposure to 80 g of alcohol (about 8 beers) over several days can
produce hepatic changes consistent with fatty liver disease.

–Fatty liver may develop after a single large binge and does not predict progression to
hepatitis
Alcohol and the Liver
•ALCOHOLIC FATTY LIVER:
–Fatty liver disease can be reversed if alcohol
consumption is stopped or significantly reduced.
–progression to fibrosis or cirrhosis occurred only in
patients who continued to ingest alcohol

–there are often no clinical symptoms, so fatty
liver may be undiagnosed. The only
complaint may be mild tender
hepatomegaly.

Alcohol and the Liver
•ALCOHOLIC FATTY LIVER:
•Pathology:
– macrovesicular fatty infiltration
–inflammatory changes are minimal
–fatty liver is not pathognomonic of ethanol ingestion:
• starvation,
•fatty liver of pregnancy,
•drug toxicity (valproic acid, tetracycline,
•antiviral agents such as zidovudine and dideoxyinosine),
•nonalcoholic steatohepatitis,
•viral hepatitis, particularly hepatitis C virus,
•Reye's syndrome,
•inborn errors of metabolism (such as defects in mitochondrial beta
oxidation)
Alcoholic Liver Disease and
Alcoholic Cirrhosis
•Alcoholic hepatitis
–fatty liver with the development of hepatitis, referred to as steatohepatitis, has
been acknowledged as a precursor for the development of cirrhosis.

–Alcoholic hepatitis results directly from alcohol abuse and is observed in as
many as 35% of heavy drinkers.

–Like other forms of hepatitis, alcoholic hepatitis can be subclinical.

–Laboratory findings are more predictive if the disease has progressed.

–Approximately 40% of patients with alcoholic hepatitis who continue to
drink will develop alcoholic cirrhosis within 1 to 2 years.
Alcohol and the Liver

•ALCOHOLIC HEPATITIS:

20. Alcohol and the Liver

Alcohol and the Liver
• There is a broad spectrum of clinical and
laboratory findings in patients with alcoholic
liver disease, ranging from asymptomatic
fatty liver to alcoholic hepatitis to end-stage
liver failure with jaundice, coagulopathy, and
encephalopathy
Loading…
Alcohol and the Liver
• FINDINGS IN ALCOHOLIC LIVER
DISEASE

–moderate alcohol intake appears to have
cardiovascular benefits

– excessive alcohol intake can be associated with
significant social and physical consequences

–for the development of cirrhosis:
•requirement for 80 grams of ethanol daily for 10 to 20
Alcohol and the liver

•In 2009, WHO listed alcohol use as one of the
leading causes of the global burden of
disease and injury, surpassed only slightly by
childhood malnourishment and unsafe sex.


•This placed alcohol use ahead of unsafe water
and sanitation, hypertension, high cholesterol,
and tobacco use, and clearly affirms that
alcohol is the most widely abused substance
Loading…
Alcoholism and the Effects of
Alcohol

•In the United States, approximately 100 000
deaths per year are attributed to alcohol abuse.

•Alcohol use is an underlying cause of more
than 30 conditions and a definite contributing
factor to many more, including
–psychotic disorder
–alcoholic cardiomyopathy
–amnesic syndrome
–alcoholic liver disease.
Alcoholism and the Effects of
Alcohol

•The Mayo Clinic defined alcoholism as a
chronic disease in which the body becomes
reliant upon alcohol (ethanol).

•Furthermore, it has been referred to as a
syndrome that consists of 2 phases:
–problem drinking
and
–alcohol addiction.

Alcoholic Liver Disease
•Beverage Alcohol

–Beer 5%

–Wine 12%

–Hard Liquor 40%
(Brandy, wisky, Rum)

–Arrack 40 – 50%
Alcoholism and the Effects of
Alcohol
•A standard alcoholic beverage has been described as any drink that
contains 14 g of pure alcohol.
•Irrespective of what form of alcohol is consumed, the greatest risk
factor appears to be the quantity of alcohol consumed.
•The definition for low-risk drinking for men and women differs,
because
–women suffer from hepatic damage and cirrhosis with considerably smaller
amounts of alcohol consumption.
–A man should not drink more than 4 drinks per day and no more than 14 drinks
per week.
–A woman should not drink more than 3 drinks per day and no more than 7 drinks
per week.
Risk for the development of ALD
Time to develop ALD = to amount of alcohol
consumed

•Men: 60-80 gm/day for 10 years

•Women: 20-40 gm/day for 10 years


Alcoholic cirrhosis, develops ONLY in 10 to 20% of
those who are chronically heavy drinkers.
Loading…
Risk for the development of ALD
•Epidemiology

–Over 90% of chronic heavy drinkers will develop
steatosis

–10 to 20% will develop alcoholic hepatitis

–ALD cause death of 1 in 50 people in Scotland

–4 fold increase in deaths from ALD in past 30
years
Risk for the development of ALD
•Risk of liver disease
–Amount of alcohol consumed
–Genetic factors
–Female sex
–Obesity
–Chronic viral hepatitis
–Nutritional impairment
–drugs
Alcohol Metabolism and the Liver
•The liver is the principal organ for alcohol metabolism.
•The body naturally recognizes ethanol alcohol as a foreign, toxic
agent that can disrupt normal homeostasis.
•When we consume ethanol, it is rapidly absorbed by the upper
gastrointestinal tract.
•Ethanol is
–diffused throughout the body, but exposure is greatest to the liver, via the
main portal vein.
–metabolized by the body in the gastric mucosa and the liver. These organs
manage an enzyme referred to as alcohol dehydrogenase, which is used by
the body to oxidize ethanol and convert it into acetaldehyde and other
metabolites.
–Acetaldehyde ultimately is converted by the body into acetic acid, and then
acetate. Acetaldehyde affects protein synthesis.
Alcohol Metabolism and the Liver


•Alcohol’s metabolites, especially acetaldehyde, damage vital liver
cells because of the excessive generation of free radicals.


•Excessive amount of this type of free radical causes oxidative
stress, which results in the body’s inability to prevent and repair
hepatic damage and the destruction of deoxyribonucleic acid.
Alcohol Metabolism and the Liver
•In addition to the immediate damage of acetaldehyde and the free
radicals, the phagocytic cells of the liver, the Kupffer cells, also
mount an immune response.
•This response is the result of an increase in toxins in the blood that
leak from the intestinal wall and enter the blood stream because of
alcohol consumption.
•The activation of Kupffer cells is responsible for early ethanol-
induced liver injury that ultimately leads to the death of
hepatocytes.
•This damage results in the manifestation of alcoholic liver disease,
and eventually to the development of fibrosis, or scar tissue, within
the liver.

Alcohol Metabolism and the Liver
•Alcohol metabolism differs dramatically between sexes.
–Women are much more likely to suffer from liver damage than men as a
result of alcohol consumption. However, this phenomenon is not clearly
understood.

•In addition to sex, the incidence of liver damage depends on the
– individual’s ethnicity
–genetic predisposition
–nutritional state.
Alcohol and the Liver
•Physical examination :

–vary from normal to evidence of cirrhosis or
hepatic decompensation
•Abdominal wall collaterals (caput medusa),
•Ascites,
•Cutaneous telangiectasias,
•Digital clubbing,
•Dupuytren's contractures,
•Gynecomastia,
•Jaundice,
•Malnutrition ,
•Palmar erythema,
•Peripheral neuropathy,
Alcohol and the Liver
•Laboratory findings:

–serum AST (SGOT), ALT (SGPT), and
gammaglutamyl transferase (GGT) are often
abnormal in alcoholic liver disease

–disproportionate elevation of serum AST (SGOT)
compared to ALT (SGPT) ratio is usually greater
than 2.0

–absolute values of serum AST and ALT are almost
always less than 500 IU/L
Alcohol and the Liver

–Consumption of alcohol can lead to a variety of
histopathologic changes in the liver ranging from
steatosis to cirrhosis
• Steatosis,
•alcoholic hepatitis,
•cirrhosis

–The mechanism behind the development of ALD is not
completely understood, because it is estimated that
only 10% to 20% of alcoholics develop cirrhosis.

Alcoholic Liver Disease
•Signs and symptoms
–Steatosis:
•usually asymptomatic, hepatomegaly

–Alcoholic hepatitis:
•malaise, jaundice, tender hepatomegaly, fever, weight
loss, abdominal discomfort

–Cirrhosis:
•similar to other causes of cirrhosis.
•Hepatomegaly, splenomegaly, malaise, jaundice, weight
loss, ascites, signs of CLD
Alcoholic Liver Disease and
Alcoholic Cirrhosis
•Hepatic steatosis;

–commonly referred to as fatty liver, is a frequent diagnosis that is not
exclusive to patients suffering from ALD.

–Fatty liver is the accumulation of triglycerides in the hepatocytes.

–Fatty liver has been demonstrated in 90% to 100% of all heavy drinkers.

–Short-term exposure to 80 g of alcohol (about 8 beers) over several days can
produce hepatic changes consistent with fatty liver disease.

–Fatty liver may develop after a single large binge and does not predict progression to
hepatitis
Alcohol and the Liver
•ALCOHOLIC FATTY LIVER:
–Fatty liver disease can be reversed if alcohol
consumption is stopped or significantly reduced.
–progression to fibrosis or cirrhosis occurred only in
patients who continued to ingest alcohol

–there are often no clinical symptoms, so fatty
liver may be undiagnosed. The only
complaint may be mild tender
hepatomegaly.

Alcohol and the Liver
•ALCOHOLIC FATTY LIVER:
•Pathology:
– macrovesicular fatty infiltration
–inflammatory changes are minimal
–fatty liver is not pathognomonic of ethanol ingestion:
• starvation,
•fatty liver of pregnancy,
•drug toxicity (valproic acid, tetracycline,
•antiviral agents such as zidovudine and dideoxyinosine),
•nonalcoholic steatohepatitis,
•viral hepatitis, particularly hepatitis C virus,
•Reye's syndrome,
•inborn errors of metabolism (such as defects in mitochondrial beta
oxidation)
Alcoholic Liver Disease and
Alcoholic Cirrhosis
•Alcoholic hepatitis
–fatty liver with the development of hepatitis, referred to as steatohepatitis, has
been acknowledged as a precursor for the development of cirrhosis.

–Alcoholic hepatitis results directly from alcohol abuse and is observed in as
many as 35% of heavy drinkers.

–Like other forms of hepatitis, alcoholic hepatitis can be subclinical.

–Laboratory findings are more predictive if the disease has progressed.

–Approximately 40% of patients with alcoholic hepatitis who continue to
drink will develop alcoholic cirrhosis within 1 to 2 years.
Alcohol and the Liver

•ALCOHOLIC HEPATITIS:

21. Alcohol and the Liver

Alcohol and the Liver
• There is a broad spectrum of clinical and
laboratory findings in patients with alcoholic
liver disease, ranging from asymptomatic
fatty liver to alcoholic hepatitis to end-stage
liver failure with jaundice, coagulopathy, and
encephalopathy
Loading…
Alcohol and the Liver
• FINDINGS IN ALCOHOLIC LIVER
DISEASE

–moderate alcohol intake appears to have
cardiovascular benefits

– excessive alcohol intake can be associated with
significant social and physical consequences

–for the development of cirrhosis:
•requirement for 80 grams of ethanol daily for 10 to 20
Alcohol and the liver

•In 2009, WHO listed alcohol use as one of the
leading causes of the global burden of
disease and injury, surpassed only slightly by
childhood malnourishment and unsafe sex.


•This placed alcohol use ahead of unsafe water
and sanitation, hypertension, high cholesterol,
and tobacco use, and clearly affirms that
alcohol is the most widely abused substance
Loading…
Alcoholism and the Effects of
Alcohol

•In the United States, approximately 100 000
deaths per year are attributed to alcohol abuse.

•Alcohol use is an underlying cause of more
than 30 conditions and a definite contributing
factor to many more, including
–psychotic disorder
–alcoholic cardiomyopathy
–amnesic syndrome
–alcoholic liver disease.
Alcoholism and the Effects of
Alcohol

•The Mayo Clinic defined alcoholism as a
chronic disease in which the body becomes
reliant upon alcohol (ethanol).

•Furthermore, it has been referred to as a
syndrome that consists of 2 phases:
–problem drinking
and
–alcohol addiction.

Alcoholic Liver Disease
•Beverage Alcohol

–Beer 5%

–Wine 12%

–Hard Liquor 40%
(Brandy, wisky, Rum)

–Arrack 40 – 50%
Alcoholism and the Effects of
Alcohol
•A standard alcoholic beverage has been described as any drink that
contains 14 g of pure alcohol.
•Irrespective of what form of alcohol is consumed, the greatest risk
factor appears to be the quantity of alcohol consumed.
•The definition for low-risk drinking for men and women differs,
because
–women suffer from hepatic damage and cirrhosis with considerably smaller
amounts of alcohol consumption.
–A man should not drink more than 4 drinks per day and no more than 14 drinks
per week.
–A woman should not drink more than 3 drinks per day and no more than 7 drinks
per week.
Risk for the development of ALD
Time to develop ALD = to amount of alcohol
consumed

•Men: 60-80 gm/day for 10 years

•Women: 20-40 gm/day for 10 years


Alcoholic cirrhosis, develops ONLY in 10 to 20% of
those who are chronically heavy drinkers.
Loading…
Risk for the development of ALD
•Epidemiology

–Over 90% of chronic heavy drinkers will develop
steatosis

–10 to 20% will develop alcoholic hepatitis

–ALD cause death of 1 in 50 people in Scotland

–4 fold increase in deaths from ALD in past 30
years
Risk for the development of ALD
•Risk of liver disease
–Amount of alcohol consumed
–Genetic factors
–Female sex
–Obesity
–Chronic viral hepatitis
–Nutritional impairment
–drugs
Alcohol Metabolism and the Liver
•The liver is the principal organ for alcohol metabolism.
•The body naturally recognizes ethanol alcohol as a foreign, toxic
agent that can disrupt normal homeostasis.
•When we consume ethanol, it is rapidly absorbed by the upper
gastrointestinal tract.
•Ethanol is
–diffused throughout the body, but exposure is greatest to the liver, via the
main portal vein.
–metabolized by the body in the gastric mucosa and the liver. These organs
manage an enzyme referred to as alcohol dehydrogenase, which is used by
the body to oxidize ethanol and convert it into acetaldehyde and other
metabolites.
–Acetaldehyde ultimately is converted by the body into acetic acid, and then
acetate. Acetaldehyde affects protein synthesis.
Alcohol Metabolism and the Liver


•Alcohol’s metabolites, especially acetaldehyde, damage vital liver
cells because of the excessive generation of free radicals.


•Excessive amount of this type of free radical causes oxidative
stress, which results in the body’s inability to prevent and repair
hepatic damage and the destruction of deoxyribonucleic acid.
Alcohol Metabolism and the Liver
•In addition to the immediate damage of acetaldehyde and the free
radicals, the phagocytic cells of the liver, the Kupffer cells, also
mount an immune response.
•This response is the result of an increase in toxins in the blood that
leak from the intestinal wall and enter the blood stream because of
alcohol consumption.
•The activation of Kupffer cells is responsible for early ethanol-
induced liver injury that ultimately leads to the death of
hepatocytes.
•This damage results in the manifestation of alcoholic liver disease,
and eventually to the development of fibrosis, or scar tissue, within
the liver.

Alcohol Metabolism and the Liver
•Alcohol metabolism differs dramatically between sexes.
–Women are much more likely to suffer from liver damage than men as a
result of alcohol consumption. However, this phenomenon is not clearly
understood.

•In addition to sex, the incidence of liver damage depends on the
– individual’s ethnicity
–genetic predisposition
–nutritional state.
Alcohol and the Liver
•Physical examination :

–vary from normal to evidence of cirrhosis or
hepatic decompensation
•Abdominal wall collaterals (caput medusa),
•Ascites,
•Cutaneous telangiectasias,
•Digital clubbing,
•Dupuytren's contractures,
•Gynecomastia,
•Jaundice,
•Malnutrition ,
•Palmar erythema,
•Peripheral neuropathy,
Alcohol and the Liver
•Laboratory findings:

–serum AST (SGOT), ALT (SGPT), and
gammaglutamyl transferase (GGT) are often
abnormal in alcoholic liver disease

–disproportionate elevation of serum AST (SGOT)
compared to ALT (SGPT) ratio is usually greater
than 2.0

–absolute values of serum AST and ALT are almost
always less than 500 IU/L
Alcohol and the Liver

–Consumption of alcohol can lead to a variety of
histopathologic changes in the liver ranging from
steatosis to cirrhosis
• Steatosis,
•alcoholic hepatitis,
•cirrhosis

–The mechanism behind the development of ALD is not
completely understood, because it is estimated that
only 10% to 20% of alcoholics develop cirrhosis.

Alcoholic Liver Disease
•Signs and symptoms
–Steatosis:
•usually asymptomatic, hepatomegaly

–Alcoholic hepatitis:
•malaise, jaundice, tender hepatomegaly, fever, weight
loss, abdominal discomfort

–Cirrhosis:
•similar to other causes of cirrhosis.
•Hepatomegaly, splenomegaly, malaise, jaundice, weight
loss, ascites, signs of CLD
Alcoholic Liver Disease and
Alcoholic Cirrhosis
•Hepatic steatosis;

–commonly referred to as fatty liver, is a frequent diagnosis that is not
exclusive to patients suffering from ALD.

–Fatty liver is the accumulation of triglycerides in the hepatocytes.

–Fatty liver has been demonstrated in 90% to 100% of all heavy drinkers.

–Short-term exposure to 80 g of alcohol (about 8 beers) over several days can
produce hepatic changes consistent with fatty liver disease.

–Fatty liver may develop after a single large binge and does not predict progression to
hepatitis
Alcohol and the Liver
•ALCOHOLIC FATTY LIVER:
–Fatty liver disease can be reversed if alcohol
consumption is stopped or significantly reduced.
–progression to fibrosis or cirrhosis occurred only in
patients who continued to ingest alcohol

–there are often no clinical symptoms, so fatty
liver may be undiagnosed. The only
complaint may be mild tender
hepatomegaly.

Alcohol and the Liver
•ALCOHOLIC FATTY LIVER:
•Pathology:
– macrovesicular fatty infiltration
–inflammatory changes are minimal
–fatty liver is not pathognomonic of ethanol ingestion:
• starvation,
•fatty liver of pregnancy,
•drug toxicity (valproic acid, tetracycline,
•antiviral agents such as zidovudine and dideoxyinosine),
•nonalcoholic steatohepatitis,
•viral hepatitis, particularly hepatitis C virus,
•Reye's syndrome,
•inborn errors of metabolism (such as defects in mitochondrial beta
oxidation)
Alcoholic Liver Disease and
Alcoholic Cirrhosis
•Alcoholic hepatitis
–fatty liver with the development of hepatitis, referred to as steatohepatitis, has
been acknowledged as a precursor for the development of cirrhosis.

–Alcoholic hepatitis results directly from alcohol abuse and is observed in as
many as 35% of heavy drinkers.

–Like other forms of hepatitis, alcoholic hepatitis can be subclinical.

–Laboratory findings are more predictive if the disease has progressed.

–Approximately 40% of patients with alcoholic hepatitis who continue to
drink will develop alcoholic cirrhosis within 1 to 2 years.
Alcohol and the Liver

•ALCOHOLIC HEPATITIS:

22. Alcohol and the Liver

Alcohol and the Liver
• There is a broad spectrum of clinical and
laboratory findings in patients with alcoholic
liver disease, ranging from asymptomatic
fatty liver to alcoholic hepatitis to end-stage
liver failure with jaundice, coagulopathy, and
encephalopathy
Loading…
Alcohol and the Liver
• FINDINGS IN ALCOHOLIC LIVER
DISEASE

–moderate alcohol intake appears to have
cardiovascular benefits

– excessive alcohol intake can be associated with
significant social and physical consequences

–for the development of cirrhosis:
•requirement for 80 grams of ethanol daily for 10 to 20
Alcohol and the liver

•In 2009, WHO listed alcohol use as one of the
leading causes of the global burden of
disease and injury, surpassed only slightly by
childhood malnourishment and unsafe sex.


•This placed alcohol use ahead of unsafe water
and sanitation, hypertension, high cholesterol,
and tobacco use, and clearly affirms that
alcohol is the most widely abused substance
Loading…
Alcoholism and the Effects of
Alcohol

•In the United States, approximately 100 000
deaths per year are attributed to alcohol abuse.

•Alcohol use is an underlying cause of more
than 30 conditions and a definite contributing
factor to many more, including
–psychotic disorder
–alcoholic cardiomyopathy
–amnesic syndrome
–alcoholic liver disease.
Alcoholism and the Effects of
Alcohol

•The Mayo Clinic defined alcoholism as a
chronic disease in which the body becomes
reliant upon alcohol (ethanol).

•Furthermore, it has been referred to as a
syndrome that consists of 2 phases:
–problem drinking
and
–alcohol addiction.

Alcoholic Liver Disease
•Beverage Alcohol

–Beer 5%

–Wine 12%

–Hard Liquor 40%
(Brandy, wisky, Rum)

–Arrack 40 – 50%
Alcoholism and the Effects of
Alcohol
•A standard alcoholic beverage has been described as any drink that
contains 14 g of pure alcohol.
•Irrespective of what form of alcohol is consumed, the greatest risk
factor appears to be the quantity of alcohol consumed.
•The definition for low-risk drinking for men and women differs,
because
–women suffer from hepatic damage and cirrhosis with considerably smaller
amounts of alcohol consumption.
–A man should not drink more than 4 drinks per day and no more than 14 drinks
per week.
–A woman should not drink more than 3 drinks per day and no more than 7 drinks
per week.
Risk for the development of ALD
Time to develop ALD = to amount of alcohol
consumed

•Men: 60-80 gm/day for 10 years

•Women: 20-40 gm/day for 10 years


Alcoholic cirrhosis, develops ONLY in 10 to 20% of
those who are chronically heavy drinkers.
Loading…
Risk for the development of ALD
•Epidemiology

–Over 90% of chronic heavy drinkers will develop
steatosis

–10 to 20% will develop alcoholic hepatitis

–ALD cause death of 1 in 50 people in Scotland

–4 fold increase in deaths from ALD in past 30
years
Risk for the development of ALD
•Risk of liver disease
–Amount of alcohol consumed
–Genetic factors
–Female sex
–Obesity
–Chronic viral hepatitis
–Nutritional impairment
–drugs
Alcohol Metabolism and the Liver
•The liver is the principal organ for alcohol metabolism.
•The body naturally recognizes ethanol alcohol as a foreign, toxic
agent that can disrupt normal homeostasis.
•When we consume ethanol, it is rapidly absorbed by the upper
gastrointestinal tract.
•Ethanol is
–diffused throughout the body, but exposure is greatest to the liver, via the
main portal vein.
–metabolized by the body in the gastric mucosa and the liver. These organs
manage an enzyme referred to as alcohol dehydrogenase, which is used by
the body to oxidize ethanol and convert it into acetaldehyde and other
metabolites.
–Acetaldehyde ultimately is converted by the body into acetic acid, and then
acetate. Acetaldehyde affects protein synthesis.
Alcohol Metabolism and the Liver


•Alcohol’s metabolites, especially acetaldehyde, damage vital liver
cells because of the excessive generation of free radicals.


•Excessive amount of this type of free radical causes oxidative
stress, which results in the body’s inability to prevent and repair
hepatic damage and the destruction of deoxyribonucleic acid.
Alcohol Metabolism and the Liver
•In addition to the immediate damage of acetaldehyde and the free
radicals, the phagocytic cells of the liver, the Kupffer cells, also
mount an immune response.
•This response is the result of an increase in toxins in the blood that
leak from the intestinal wall and enter the blood stream because of
alcohol consumption.
•The activation of Kupffer cells is responsible for early ethanol-
induced liver injury that ultimately leads to the death of
hepatocytes.
•This damage results in the manifestation of alcoholic liver disease,
and eventually to the development of fibrosis, or scar tissue, within
the liver.

Alcohol Metabolism and the Liver
•Alcohol metabolism differs dramatically between sexes.
–Women are much more likely to suffer from liver damage than men as a
result of alcohol consumption. However, this phenomenon is not clearly
understood.

•In addition to sex, the incidence of liver damage depends on the
– individual’s ethnicity
–genetic predisposition
–nutritional state.
Alcohol and the Liver
•Physical examination :

–vary from normal to evidence of cirrhosis or
hepatic decompensation
•Abdominal wall collaterals (caput medusa),
•Ascites,
•Cutaneous telangiectasias,
•Digital clubbing,
•Dupuytren's contractures,
•Gynecomastia,
•Jaundice,
•Malnutrition ,
•Palmar erythema,
•Peripheral neuropathy,
Alcohol and the Liver
•Laboratory findings:

–serum AST (SGOT), ALT (SGPT), and
gammaglutamyl transferase (GGT) are often
abnormal in alcoholic liver disease

–disproportionate elevation of serum AST (SGOT)
compared to ALT (SGPT) ratio is usually greater
than 2.0

–absolute values of serum AST and ALT are almost
always less than 500 IU/L
Alcohol and the Liver

–Consumption of alcohol can lead to a variety of
histopathologic changes in the liver ranging from
steatosis to cirrhosis
• Steatosis,
•alcoholic hepatitis,
•cirrhosis

–The mechanism behind the development of ALD is not
completely understood, because it is estimated that
only 10% to 20% of alcoholics develop cirrhosis.

Alcoholic Liver Disease
•Signs and symptoms
–Steatosis:
•usually asymptomatic, hepatomegaly

–Alcoholic hepatitis:
•malaise, jaundice, tender hepatomegaly, fever, weight
loss, abdominal discomfort

–Cirrhosis:
•similar to other causes of cirrhosis.
•Hepatomegaly, splenomegaly, malaise, jaundice, weight
loss, ascites, signs of CLD
Alcoholic Liver Disease and
Alcoholic Cirrhosis
•Hepatic steatosis;

–commonly referred to as fatty liver, is a frequent diagnosis that is not
exclusive to patients suffering from ALD.

–Fatty liver is the accumulation of triglycerides in the hepatocytes.

–Fatty liver has been demonstrated in 90% to 100% of all heavy drinkers.

–Short-term exposure to 80 g of alcohol (about 8 beers) over several days can
produce hepatic changes consistent with fatty liver disease.

–Fatty liver may develop after a single large binge and does not predict progression to
hepatitis
Alcohol and the Liver
•ALCOHOLIC FATTY LIVER:
–Fatty liver disease can be reversed if alcohol
consumption is stopped or significantly reduced.
–progression to fibrosis or cirrhosis occurred only in
patients who continued to ingest alcohol

–there are often no clinical symptoms, so fatty
liver may be undiagnosed. The only
complaint may be mild tender
hepatomegaly.

Alcohol and the Liver
•ALCOHOLIC FATTY LIVER:
•Pathology:
– macrovesicular fatty infiltration
–inflammatory changes are minimal
–fatty liver is not pathognomonic of ethanol ingestion:
• starvation,
•fatty liver of pregnancy,
•drug toxicity (valproic acid, tetracycline,
•antiviral agents such as zidovudine and dideoxyinosine),
•nonalcoholic steatohepatitis,
•viral hepatitis, particularly hepatitis C virus,
•Reye's syndrome,
•inborn errors of metabolism (such as defects in mitochondrial beta
oxidation)
Alcoholic Liver Disease and
Alcoholic Cirrhosis
•Alcoholic hepatitis
–fatty liver with the development of hepatitis, referred to as steatohepatitis, has
been acknowledged as a precursor for the development of cirrhosis.

–Alcoholic hepatitis results directly from alcohol abuse and is observed in as
many as 35% of heavy drinkers.

–Like other forms of hepatitis, alcoholic hepatitis can be subclinical.

–Laboratory findings are more predictive if the disease has progressed.

–Approximately 40% of patients with alcoholic hepatitis who continue to
drink will develop alcoholic cirrhosis within 1 to 2 years.
Alcohol and the Liver

•ALCOHOLIC HEPATITIS:

23. Alcohol and the Liver

Alcohol and the Liver
• There is a broad spectrum of clinical and
laboratory findings in patients with alcoholic
liver disease, ranging from asymptomatic
fatty liver to alcoholic hepatitis to end-stage
liver failure with jaundice, coagulopathy, and
encephalopathy
Loading…
Alcohol and the Liver
• FINDINGS IN ALCOHOLIC LIVER
DISEASE

–moderate alcohol intake appears to have
cardiovascular benefits

– excessive alcohol intake can be associated with
significant social and physical consequences

–for the development of cirrhosis:
•requirement for 80 grams of ethanol daily for 10 to 20
Alcohol and the liver

•In 2009, WHO listed alcohol use as one of the
leading causes of the global burden of
disease and injury, surpassed only slightly by
childhood malnourishment and unsafe sex.


•This placed alcohol use ahead of unsafe water
and sanitation, hypertension, high cholesterol,
and tobacco use, and clearly affirms that
alcohol is the most widely abused substance
Loading…
Alcoholism and the Effects of
Alcohol

•In the United States, approximately 100 000
deaths per year are attributed to alcohol abuse.

•Alcohol use is an underlying cause of more
than 30 conditions and a definite contributing
factor to many more, including
–psychotic disorder
–alcoholic cardiomyopathy
–amnesic syndrome
–alcoholic liver disease.
Alcoholism and the Effects of
Alcohol

•The Mayo Clinic defined alcoholism as a
chronic disease in which the body becomes
reliant upon alcohol (ethanol).

•Furthermore, it has been referred to as a
syndrome that consists of 2 phases:
–problem drinking
and
–alcohol addiction.

Alcoholic Liver Disease
•Beverage Alcohol

–Beer 5%

–Wine 12%

–Hard Liquor 40%
(Brandy, wisky, Rum)

–Arrack 40 – 50%
Alcoholism and the Effects of
Alcohol
•A standard alcoholic beverage has been described as any drink that
contains 14 g of pure alcohol.
•Irrespective of what form of alcohol is consumed, the greatest risk
factor appears to be the quantity of alcohol consumed.
•The definition for low-risk drinking for men and women differs,
because
–women suffer from hepatic damage and cirrhosis with considerably smaller
amounts of alcohol consumption.
–A man should not drink more than 4 drinks per day and no more than 14 drinks
per week.
–A woman should not drink more than 3 drinks per day and no more than 7 drinks
per week.
Risk for the development of ALD
Time to develop ALD = to amount of alcohol
consumed

•Men: 60-80 gm/day for 10 years

•Women: 20-40 gm/day for 10 years


Alcoholic cirrhosis, develops ONLY in 10 to 20% of
those who are chronically heavy drinkers.
Loading…
Risk for the development of ALD
•Epidemiology

–Over 90% of chronic heavy drinkers will develop
steatosis

–10 to 20% will develop alcoholic hepatitis

–ALD cause death of 1 in 50 people in Scotland

–4 fold increase in deaths from ALD in past 30
years
Risk for the development of ALD
•Risk of liver disease
–Amount of alcohol consumed
–Genetic factors
–Female sex
–Obesity
–Chronic viral hepatitis
–Nutritional impairment
–drugs
Alcohol Metabolism and the Liver
•The liver is the principal organ for alcohol metabolism.
•The body naturally recognizes ethanol alcohol as a foreign, toxic
agent that can disrupt normal homeostasis.
•When we consume ethanol, it is rapidly absorbed by the upper
gastrointestinal tract.
•Ethanol is
–diffused throughout the body, but exposure is greatest to the liver, via the
main portal vein.
–metabolized by the body in the gastric mucosa and the liver. These organs
manage an enzyme referred to as alcohol dehydrogenase, which is used by
the body to oxidize ethanol and convert it into acetaldehyde and other
metabolites.
–Acetaldehyde ultimately is converted by the body into acetic acid, and then
acetate. Acetaldehyde affects protein synthesis.
Alcohol Metabolism and the Liver


•Alcohol’s metabolites, especially acetaldehyde, damage vital liver
cells because of the excessive generation of free radicals.


•Excessive amount of this type of free radical causes oxidative
stress, which results in the body’s inability to prevent and repair
hepatic damage and the destruction of deoxyribonucleic acid.
Alcohol Metabolism and the Liver
•In addition to the immediate damage of acetaldehyde and the free
radicals, the phagocytic cells of the liver, the Kupffer cells, also
mount an immune response.
•This response is the result of an increase in toxins in the blood that
leak from the intestinal wall and enter the blood stream because of
alcohol consumption.
•The activation of Kupffer cells is responsible for early ethanol-
induced liver injury that ultimately leads to the death of
hepatocytes.
•This damage results in the manifestation of alcoholic liver disease,
and eventually to the development of fibrosis, or scar tissue, within
the liver.

Alcohol Metabolism and the Liver
•Alcohol metabolism differs dramatically between sexes.
–Women are much more likely to suffer from liver damage than men as a
result of alcohol consumption. However, this phenomenon is not clearly
understood.

•In addition to sex, the incidence of liver damage depends on the
– individual’s ethnicity
–genetic predisposition
–nutritional state.
Alcohol and the Liver
•Physical examination :

–vary from normal to evidence of cirrhosis or
hepatic decompensation
•Abdominal wall collaterals (caput medusa),
•Ascites,
•Cutaneous telangiectasias,
•Digital clubbing,
•Dupuytren's contractures,
•Gynecomastia,
•Jaundice,
•Malnutrition ,
•Palmar erythema,
•Peripheral neuropathy,
Alcohol and the Liver
•Laboratory findings:

–serum AST (SGOT), ALT (SGPT), and
gammaglutamyl transferase (GGT) are often
abnormal in alcoholic liver disease

–disproportionate elevation of serum AST (SGOT)
compared to ALT (SGPT) ratio is usually greater
than 2.0

–absolute values of serum AST and ALT are almost
always less than 500 IU/L
Alcohol and the Liver

–Consumption of alcohol can lead to a variety of
histopathologic changes in the liver ranging from
steatosis to cirrhosis
• Steatosis,
•alcoholic hepatitis,
•cirrhosis

–The mechanism behind the development of ALD is not
completely understood, because it is estimated that
only 10% to 20% of alcoholics develop cirrhosis.

Alcoholic Liver Disease
•Signs and symptoms
–Steatosis:
•usually asymptomatic, hepatomegaly

–Alcoholic hepatitis:
•malaise, jaundice, tender hepatomegaly, fever, weight
loss, abdominal discomfort

–Cirrhosis:
•similar to other causes of cirrhosis.
•Hepatomegaly, splenomegaly, malaise, jaundice, weight
loss, ascites, signs of CLD
Alcoholic Liver Disease and
Alcoholic Cirrhosis
•Hepatic steatosis;

–commonly referred to as fatty liver, is a frequent diagnosis that is not
exclusive to patients suffering from ALD.

–Fatty liver is the accumulation of triglycerides in the hepatocytes.

–Fatty liver has been demonstrated in 90% to 100% of all heavy drinkers.

–Short-term exposure to 80 g of alcohol (about 8 beers) over several days can
produce hepatic changes consistent with fatty liver disease.

–Fatty liver may develop after a single large binge and does not predict progression to
hepatitis
Alcohol and the Liver
•ALCOHOLIC FATTY LIVER:
–Fatty liver disease can be reversed if alcohol
consumption is stopped or significantly reduced.
–progression to fibrosis or cirrhosis occurred only in
patients who continued to ingest alcohol

–there are often no clinical symptoms, so fatty
liver may be undiagnosed. The only
complaint may be mild tender
hepatomegaly.

Alcohol and the Liver
•ALCOHOLIC FATTY LIVER:
•Pathology:
– macrovesicular fatty infiltration
–inflammatory changes are minimal
–fatty liver is not pathognomonic of ethanol ingestion:
• starvation,
•fatty liver of pregnancy,
•drug toxicity (valproic acid, tetracycline,
•antiviral agents such as zidovudine and dideoxyinosine),
•nonalcoholic steatohepatitis,
•viral hepatitis, particularly hepatitis C virus,
•Reye's syndrome,
•inborn errors of metabolism (such as defects in mitochondrial beta
oxidation)
Alcoholic Liver Disease and
Alcoholic Cirrhosis
•Alcoholic hepatitis
–fatty liver with the development of hepatitis, referred to as steatohepatitis, has
been acknowledged as a precursor for the development of cirrhosis.

–Alcoholic hepatitis results directly from alcohol abuse and is observed in as
many as 35% of heavy drinkers.

–Like other forms of hepatitis, alcoholic hepatitis can be subclinical.

–Laboratory findings are more predictive if the disease has progressed.

–Approximately 40% of patients with alcoholic hepatitis who continue to
drink will develop alcoholic cirrhosis within 1 to 2 years.
Alcohol and the Liver

•ALCOHOLIC HEPATITIS:

24. Alcohol and the Liver

Alcohol and the Liver
• There is a broad spectrum of clinical and
laboratory findings in patients with alcoholic
liver disease, ranging from asymptomatic
fatty liver to alcoholic hepatitis to end-stage
liver failure with jaundice, coagulopathy, and
encephalopathy
Loading…
Alcohol and the Liver
• FINDINGS IN ALCOHOLIC LIVER
DISEASE

–moderate alcohol intake appears to have
cardiovascular benefits

– excessive alcohol intake can be associated with
significant social and physical consequences

–for the development of cirrhosis:
•requirement for 80 grams of ethanol daily for 10 to 20
Alcohol and the liver

•In 2009, WHO listed alcohol use as one of the
leading causes of the global burden of
disease and injury, surpassed only slightly by
childhood malnourishment and unsafe sex.


•This placed alcohol use ahead of unsafe water
and sanitation, hypertension, high cholesterol,
and tobacco use, and clearly affirms that
alcohol is the most widely abused substance
Loading…
Alcoholism and the Effects of
Alcohol

•In the United States, approximately 100 000
deaths per year are attributed to alcohol abuse.

•Alcohol use is an underlying cause of more
than 30 conditions and a definite contributing
factor to many more, including
–psychotic disorder
–alcoholic cardiomyopathy
–amnesic syndrome
–alcoholic liver disease.
Alcoholism and the Effects of
Alcohol

•The Mayo Clinic defined alcoholism as a
chronic disease in which the body becomes
reliant upon alcohol (ethanol).

•Furthermore, it has been referred to as a
syndrome that consists of 2 phases:
–problem drinking
and
–alcohol addiction.

Alcoholic Liver Disease
•Beverage Alcohol

–Beer 5%

–Wine 12%

–Hard Liquor 40%
(Brandy, wisky, Rum)

–Arrack 40 – 50%
Alcoholism and the Effects of
Alcohol
•A standard alcoholic beverage has been described as any drink that
contains 14 g of pure alcohol.
•Irrespective of what form of alcohol is consumed, the greatest risk
factor appears to be the quantity of alcohol consumed.
•The definition for low-risk drinking for men and women differs,
because
–women suffer from hepatic damage and cirrhosis with considerably smaller
amounts of alcohol consumption.
–A man should not drink more than 4 drinks per day and no more than 14 drinks
per week.
–A woman should not drink more than 3 drinks per day and no more than 7 drinks
per week.
Risk for the development of ALD
Time to develop ALD = to amount of alcohol
consumed

•Men: 60-80 gm/day for 10 years

•Women: 20-40 gm/day for 10 years


Alcoholic cirrhosis, develops ONLY in 10 to 20% of
those who are chronically heavy drinkers.
Loading…
Risk for the development of ALD
•Epidemiology

–Over 90% of chronic heavy drinkers will develop
steatosis

–10 to 20% will develop alcoholic hepatitis

–ALD cause death of 1 in 50 people in Scotland

–4 fold increase in deaths from ALD in past 30
years
Risk for the development of ALD
•Risk of liver disease
–Amount of alcohol consumed
–Genetic factors
–Female sex
–Obesity
–Chronic viral hepatitis
–Nutritional impairment
–drugs
Alcohol Metabolism and the Liver
•The liver is the principal organ for alcohol metabolism.
•The body naturally recognizes ethanol alcohol as a foreign, toxic
agent that can disrupt normal homeostasis.
•When we consume ethanol, it is rapidly absorbed by the upper
gastrointestinal tract.
•Ethanol is
–diffused throughout the body, but exposure is greatest to the liver, via the
main portal vein.
–metabolized by the body in the gastric mucosa and the liver. These organs
manage an enzyme referred to as alcohol dehydrogenase, which is used by
the body to oxidize ethanol and convert it into acetaldehyde and other
metabolites.
–Acetaldehyde ultimately is converted by the body into acetic acid, and then
acetate. Acetaldehyde affects protein synthesis.
Alcohol Metabolism and the Liver


•Alcohol’s metabolites, especially acetaldehyde, damage vital liver
cells because of the excessive generation of free radicals.


•Excessive amount of this type of free radical causes oxidative
stress, which results in the body’s inability to prevent and repair
hepatic damage and the destruction of deoxyribonucleic acid.
Alcohol Metabolism and the Liver
•In addition to the immediate damage of acetaldehyde and the free
radicals, the phagocytic cells of the liver, the Kupffer cells, also
mount an immune response.
•This response is the result of an increase in toxins in the blood that
leak from the intestinal wall and enter the blood stream because of
alcohol consumption.
•The activation of Kupffer cells is responsible for early ethanol-
induced liver injury that ultimately leads to the death of
hepatocytes.
•This damage results in the manifestation of alcoholic liver disease,
and eventually to the development of fibrosis, or scar tissue, within
the liver.

Alcohol Metabolism and the Liver
•Alcohol metabolism differs dramatically between sexes.
–Women are much more likely to suffer from liver damage than men as a
result of alcohol consumption. However, this phenomenon is not clearly
understood.

•In addition to sex, the incidence of liver damage depends on the
– individual’s ethnicity
–genetic predisposition
–nutritional state.
Alcohol and the Liver
•Physical examination :

–vary from normal to evidence of cirrhosis or
hepatic decompensation
•Abdominal wall collaterals (caput medusa),
•Ascites,
•Cutaneous telangiectasias,
•Digital clubbing,
•Dupuytren's contractures,
•Gynecomastia,
•Jaundice,
•Malnutrition ,
•Palmar erythema,
•Peripheral neuropathy,
Alcohol and the Liver
•Laboratory findings:

–serum AST (SGOT), ALT (SGPT), and
gammaglutamyl transferase (GGT) are often
abnormal in alcoholic liver disease

–disproportionate elevation of serum AST (SGOT)
compared to ALT (SGPT) ratio is usually greater
than 2.0

–absolute values of serum AST and ALT are almost
always less than 500 IU/L
Alcohol and the Liver

–Consumption of alcohol can lead to a variety of
histopathologic changes in the liver ranging from
steatosis to cirrhosis
• Steatosis,
•alcoholic hepatitis,
•cirrhosis

–The mechanism behind the development of ALD is not
completely understood, because it is estimated that
only 10% to 20% of alcoholics develop cirrhosis.

Alcoholic Liver Disease
•Signs and symptoms
–Steatosis:
•usually asymptomatic, hepatomegaly

–Alcoholic hepatitis:
•malaise, jaundice, tender hepatomegaly, fever, weight
loss, abdominal discomfort

–Cirrhosis:
•similar to other causes of cirrhosis.
•Hepatomegaly, splenomegaly, malaise, jaundice, weight
loss, ascites, signs of CLD
Alcoholic Liver Disease and
Alcoholic Cirrhosis
•Hepatic steatosis;

–commonly referred to as fatty liver, is a frequent diagnosis that is not
exclusive to patients suffering from ALD.

–Fatty liver is the accumulation of triglycerides in the hepatocytes.

–Fatty liver has been demonstrated in 90% to 100% of all heavy drinkers.

–Short-term exposure to 80 g of alcohol (about 8 beers) over several days can
produce hepatic changes consistent with fatty liver disease.

–Fatty liver may develop after a single large binge and does not predict progression to
hepatitis
Alcohol and the Liver
•ALCOHOLIC FATTY LIVER:
–Fatty liver disease can be reversed if alcohol
consumption is stopped or significantly reduced.
–progression to fibrosis or cirrhosis occurred only in
patients who continued to ingest alcohol

–there are often no clinical symptoms, so fatty
liver may be undiagnosed. The only
complaint may be mild tender
hepatomegaly.

Alcohol and the Liver
•ALCOHOLIC FATTY LIVER:
•Pathology:
– macrovesicular fatty infiltration
–inflammatory changes are minimal
–fatty liver is not pathognomonic of ethanol ingestion:
• starvation,
•fatty liver of pregnancy,
•drug toxicity (valproic acid, tetracycline,
•antiviral agents such as zidovudine and dideoxyinosine),
•nonalcoholic steatohepatitis,
•viral hepatitis, particularly hepatitis C virus,
•Reye's syndrome,
•inborn errors of metabolism (such as defects in mitochondrial beta
oxidation)
Alcoholic Liver Disease and
Alcoholic Cirrhosis
•Alcoholic hepatitis
–fatty liver with the development of hepatitis, referred to as steatohepatitis, has
been acknowledged as a precursor for the development of cirrhosis.

–Alcoholic hepatitis results directly from alcohol abuse and is observed in as
many as 35% of heavy drinkers.

–Like other forms of hepatitis, alcoholic hepatitis can be subclinical.

–Laboratory findings are more predictive if the disease has progressed.

–Approximately 40% of patients with alcoholic hepatitis who continue to
drink will develop alcoholic cirrhosis within 1 to 2 years.
Alcohol and the Liver

•ALCOHOLIC HEPATITIS:

25. Alcohol and the Liver

Alcohol and the Liver
• There is a broad spectrum of clinical and
laboratory findings in patients with alcoholic
liver disease, ranging from asymptomatic
fatty liver to alcoholic hepatitis to end-stage
liver failure with jaundice, coagulopathy, and
encephalopathy
Loading…
Alcohol and the Liver
• FINDINGS IN ALCOHOLIC LIVER
DISEASE

–moderate alcohol intake appears to have
cardiovascular benefits

– excessive alcohol intake can be associated with
significant social and physical consequences

–for the development of cirrhosis:
•requirement for 80 grams of ethanol daily for 10 to 20
Alcohol and the liver

•In 2009, WHO listed alcohol use as one of the
leading causes of the global burden of
disease and injury, surpassed only slightly by
childhood malnourishment and unsafe sex.


•This placed alcohol use ahead of unsafe water
and sanitation, hypertension, high cholesterol,
and tobacco use, and clearly affirms that
alcohol is the most widely abused substance
Loading…
Alcoholism and the Effects of
Alcohol

•In the United States, approximately 100 000
deaths per year are attributed to alcohol abuse.

•Alcohol use is an underlying cause of more
than 30 conditions and a definite contributing
factor to many more, including
–psychotic disorder
–alcoholic cardiomyopathy
–amnesic syndrome
–alcoholic liver disease.
Alcoholism and the Effects of
Alcohol

•The Mayo Clinic defined alcoholism as a
chronic disease in which the body becomes
reliant upon alcohol (ethanol).

•Furthermore, it has been referred to as a
syndrome that consists of 2 phases:
–problem drinking
and
–alcohol addiction.

Alcoholic Liver Disease
•Beverage Alcohol

–Beer 5%

–Wine 12%

–Hard Liquor 40%
(Brandy, wisky, Rum)

–Arrack 40 – 50%
Alcoholism and the Effects of
Alcohol
•A standard alcoholic beverage has been described as any drink that
contains 14 g of pure alcohol.
•Irrespective of what form of alcohol is consumed, the greatest risk
factor appears to be the quantity of alcohol consumed.
•The definition for low-risk drinking for men and women differs,
because
–women suffer from hepatic damage and cirrhosis with considerably smaller
amounts of alcohol consumption.
–A man should not drink more than 4 drinks per day and no more than 14 drinks
per week.
–A woman should not drink more than 3 drinks per day and no more than 7 drinks
per week.
Risk for the development of ALD
Time to develop ALD = to amount of alcohol
consumed

•Men: 60-80 gm/day for 10 years

•Women: 20-40 gm/day for 10 years


Alcoholic cirrhosis, develops ONLY in 10 to 20% of
those who are chronically heavy drinkers.
Loading…
Risk for the development of ALD
•Epidemiology

–Over 90% of chronic heavy drinkers will develop
steatosis

–10 to 20% will develop alcoholic hepatitis

–ALD cause death of 1 in 50 people in Scotland

–4 fold increase in deaths from ALD in past 30
years
Risk for the development of ALD
•Risk of liver disease
–Amount of alcohol consumed
–Genetic factors
–Female sex
–Obesity
–Chronic viral hepatitis
–Nutritional impairment
–drugs
Alcohol Metabolism and the Liver
•The liver is the principal organ for alcohol metabolism.
•The body naturally recognizes ethanol alcohol as a foreign, toxic
agent that can disrupt normal homeostasis.
•When we consume ethanol, it is rapidly absorbed by the upper
gastrointestinal tract.
•Ethanol is
–diffused throughout the body, but exposure is greatest to the liver, via the
main portal vein.
–metabolized by the body in the gastric mucosa and the liver. These organs
manage an enzyme referred to as alcohol dehydrogenase, which is used by
the body to oxidize ethanol and convert it into acetaldehyde and other
metabolites.
–Acetaldehyde ultimately is converted by the body into acetic acid, and then
acetate. Acetaldehyde affects protein synthesis.
Alcohol Metabolism and the Liver


•Alcohol’s metabolites, especially acetaldehyde, damage vital liver
cells because of the excessive generation of free radicals.


•Excessive amount of this type of free radical causes oxidative
stress, which results in the body’s inability to prevent and repair
hepatic damage and the destruction of deoxyribonucleic acid.
Alcohol Metabolism and the Liver
•In addition to the immediate damage of acetaldehyde and the free
radicals, the phagocytic cells of the liver, the Kupffer cells, also
mount an immune response.
•This response is the result of an increase in toxins in the blood that
leak from the intestinal wall and enter the blood stream because of
alcohol consumption.
•The activation of Kupffer cells is responsible for early ethanol-
induced liver injury that ultimately leads to the death of
hepatocytes.
•This damage results in the manifestation of alcoholic liver disease,
and eventually to the development of fibrosis, or scar tissue, within
the liver.

Alcohol Metabolism and the Liver
•Alcohol metabolism differs dramatically between sexes.
–Women are much more likely to suffer from liver damage than men as a
result of alcohol consumption. However, this phenomenon is not clearly
understood.

•In addition to sex, the incidence of liver damage depends on the
– individual’s ethnicity
–genetic predisposition
–nutritional state.
Alcohol and the Liver
•Physical examination :

–vary from normal to evidence of cirrhosis or
hepatic decompensation
•Abdominal wall collaterals (caput medusa),
•Ascites,
•Cutaneous telangiectasias,
•Digital clubbing,
•Dupuytren's contractures,
•Gynecomastia,
•Jaundice,
•Malnutrition ,
•Palmar erythema,
•Peripheral neuropathy,
Alcohol and the Liver
•Laboratory findings:

–serum AST (SGOT), ALT (SGPT), and
gammaglutamyl transferase (GGT) are often
abnormal in alcoholic liver disease

–disproportionate elevation of serum AST (SGOT)
compared to ALT (SGPT) ratio is usually greater
than 2.0

–absolute values of serum AST and ALT are almost
always less than 500 IU/L
Alcohol and the Liver

–Consumption of alcohol can lead to a variety of
histopathologic changes in the liver ranging from
steatosis to cirrhosis
• Steatosis,
•alcoholic hepatitis,
•cirrhosis

–The mechanism behind the development of ALD is not
completely understood, because it is estimated that
only 10% to 20% of alcoholics develop cirrhosis.

Alcoholic Liver Disease
•Signs and symptoms
–Steatosis:
•usually asymptomatic, hepatomegaly

–Alcoholic hepatitis:
•malaise, jaundice, tender hepatomegaly, fever, weight
loss, abdominal discomfort

–Cirrhosis:
•similar to other causes of cirrhosis.
•Hepatomegaly, splenomegaly, malaise, jaundice, weight
loss, ascites, signs of CLD
Alcoholic Liver Disease and
Alcoholic Cirrhosis
•Hepatic steatosis;

–commonly referred to as fatty liver, is a frequent diagnosis that is not
exclusive to patients suffering from ALD.

–Fatty liver is the accumulation of triglycerides in the hepatocytes.

–Fatty liver has been demonstrated in 90% to 100% of all heavy drinkers.

–Short-term exposure to 80 g of alcohol (about 8 beers) over several days can
produce hepatic changes consistent with fatty liver disease.

–Fatty liver may develop after a single large binge and does not predict progression to
hepatitis
Alcohol and the Liver
•ALCOHOLIC FATTY LIVER:
–Fatty liver disease can be reversed if alcohol
consumption is stopped or significantly reduced.
–progression to fibrosis or cirrhosis occurred only in
patients who continued to ingest alcohol

–there are often no clinical symptoms, so fatty
liver may be undiagnosed. The only
complaint may be mild tender
hepatomegaly.

Alcohol and the Liver
•ALCOHOLIC FATTY LIVER:
•Pathology:
– macrovesicular fatty infiltration
–inflammatory changes are minimal
–fatty liver is not pathognomonic of ethanol ingestion:
• starvation,
•fatty liver of pregnancy,
•drug toxicity (valproic acid, tetracycline,
•antiviral agents such as zidovudine and dideoxyinosine),
•nonalcoholic steatohepatitis,
•viral hepatitis, particularly hepatitis C virus,
•Reye's syndrome,
•inborn errors of metabolism (such as defects in mitochondrial beta
oxidation)
Alcoholic Liver Disease and
Alcoholic Cirrhosis
•Alcoholic hepatitis
–fatty liver with the development of hepatitis, referred to as steatohepatitis, has
been acknowledged as a precursor for the development of cirrhosis.

–Alcoholic hepatitis results directly from alcohol abuse and is observed in as
many as 35% of heavy drinkers.

–Like other forms of hepatitis, alcoholic hepatitis can be subclinical.

–Laboratory findings are more predictive if the disease has progressed.

–Approximately 40% of patients with alcoholic hepatitis who continue to
drink will develop alcoholic cirrhosis within 1 to 2 years.
Alcohol and the Liver

•ALCOHOLIC HEPATITIS:

26. Alcohol and the Liver

Alcohol and the Liver
• There is a broad spectrum of clinical and
laboratory findings in patients with alcoholic
liver disease, ranging from asymptomatic
fatty liver to alcoholic hepatitis to end-stage
liver failure with jaundice, coagulopathy, and
encephalopathy
Loading…
Alcohol and the Liver
• FINDINGS IN ALCOHOLIC LIVER
DISEASE

–moderate alcohol intake appears to have
cardiovascular benefits

– excessive alcohol intake can be associated with
significant social and physical consequences

–for the development of cirrhosis:
•requirement for 80 grams of ethanol daily for 10 to 20
Alcohol and the liver

•In 2009, WHO listed alcohol use as one of the
leading causes of the global burden of
disease and injury, surpassed only slightly by
childhood malnourishment and unsafe sex.


•This placed alcohol use ahead of unsafe water
and sanitation, hypertension, high cholesterol,
and tobacco use, and clearly affirms that
alcohol is the most widely abused substance
Loading…
Alcoholism and the Effects of
Alcohol

•In the United States, approximately 100 000
deaths per year are attributed to alcohol abuse.

•Alcohol use is an underlying cause of more
than 30 conditions and a definite contributing
factor to many more, including
–psychotic disorder
–alcoholic cardiomyopathy
–amnesic syndrome
–alcoholic liver disease.
Alcoholism and the Effects of
Alcohol

•The Mayo Clinic defined alcoholism as a
chronic disease in which the body becomes
reliant upon alcohol (ethanol).

•Furthermore, it has been referred to as a
syndrome that consists of 2 phases:
–problem drinking
and
–alcohol addiction.

Alcoholic Liver Disease
•Beverage Alcohol

–Beer 5%

–Wine 12%

–Hard Liquor 40%
(Brandy, wisky, Rum)

–Arrack 40 – 50%
Alcoholism and the Effects of
Alcohol
•A standard alcoholic beverage has been described as any drink that
contains 14 g of pure alcohol.
•Irrespective of what form of alcohol is consumed, the greatest risk
factor appears to be the quantity of alcohol consumed.
•The definition for low-risk drinking for men and women differs,
because
–women suffer from hepatic damage and cirrhosis with considerably smaller
amounts of alcohol consumption.
–A man should not drink more than 4 drinks per day and no more than 14 drinks
per week.
–A woman should not drink more than 3 drinks per day and no more than 7 drinks
per week.
Risk for the development of ALD
Time to develop ALD = to amount of alcohol
consumed

•Men: 60-80 gm/day for 10 years

•Women: 20-40 gm/day for 10 years


Alcoholic cirrhosis, develops ONLY in 10 to 20% of
those who are chronically heavy drinkers.
Loading…
Risk for the development of ALD
•Epidemiology

–Over 90% of chronic heavy drinkers will develop
steatosis

–10 to 20% will develop alcoholic hepatitis

–ALD cause death of 1 in 50 people in Scotland

–4 fold increase in deaths from ALD in past 30
years
Risk for the development of ALD
•Risk of liver disease
–Amount of alcohol consumed
–Genetic factors
–Female sex
–Obesity
–Chronic viral hepatitis
–Nutritional impairment
–drugs
Alcohol Metabolism and the Liver
•The liver is the principal organ for alcohol metabolism.
•The body naturally recognizes ethanol alcohol as a foreign, toxic
agent that can disrupt normal homeostasis.
•When we consume ethanol, it is rapidly absorbed by the upper
gastrointestinal tract.
•Ethanol is
–diffused throughout the body, but exposure is greatest to the liver, via the
main portal vein.
–metabolized by the body in the gastric mucosa and the liver. These organs
manage an enzyme referred to as alcohol dehydrogenase, which is used by
the body to oxidize ethanol and convert it into acetaldehyde and other
metabolites.
–Acetaldehyde ultimately is converted by the body into acetic acid, and then
acetate. Acetaldehyde affects protein synthesis.
Alcohol Metabolism and the Liver


•Alcohol’s metabolites, especially acetaldehyde, damage vital liver
cells because of the excessive generation of free radicals.


•Excessive amount of this type of free radical causes oxidative
stress, which results in the body’s inability to prevent and repair
hepatic damage and the destruction of deoxyribonucleic acid.
Alcohol Metabolism and the Liver
•In addition to the immediate damage of acetaldehyde and the free
radicals, the phagocytic cells of the liver, the Kupffer cells, also
mount an immune response.
•This response is the result of an increase in toxins in the blood that
leak from the intestinal wall and enter the blood stream because of
alcohol consumption.
•The activation of Kupffer cells is responsible for early ethanol-
induced liver injury that ultimately leads to the death of
hepatocytes.
•This damage results in the manifestation of alcoholic liver disease,
and eventually to the development of fibrosis, or scar tissue, within
the liver.

Alcohol Metabolism and the Liver
•Alcohol metabolism differs dramatically between sexes.
–Women are much more likely to suffer from liver damage than men as a
result of alcohol consumption. However, this phenomenon is not clearly
understood.

•In addition to sex, the incidence of liver damage depends on the
– individual’s ethnicity
–genetic predisposition
–nutritional state.
Alcohol and the Liver
•Physical examination :

–vary from normal to evidence of cirrhosis or
hepatic decompensation
•Abdominal wall collaterals (caput medusa),
•Ascites,
•Cutaneous telangiectasias,
•Digital clubbing,
•Dupuytren's contractures,
•Gynecomastia,
•Jaundice,
•Malnutrition ,
•Palmar erythema,
•Peripheral neuropathy,
Alcohol and the Liver
•Laboratory findings:

–serum AST (SGOT), ALT (SGPT), and
gammaglutamyl transferase (GGT) are often
abnormal in alcoholic liver disease

–disproportionate elevation of serum AST (SGOT)
compared to ALT (SGPT) ratio is usually greater
than 2.0

–absolute values of serum AST and ALT are almost
always less than 500 IU/L
Alcohol and the Liver

–Consumption of alcohol can lead to a variety of
histopathologic changes in the liver ranging from
steatosis to cirrhosis
• Steatosis,
•alcoholic hepatitis,
•cirrhosis

–The mechanism behind the development of ALD is not
completely understood, because it is estimated that
only 10% to 20% of alcoholics develop cirrhosis.

Alcoholic Liver Disease
•Signs and symptoms
–Steatosis:
•usually asymptomatic, hepatomegaly

–Alcoholic hepatitis:
•malaise, jaundice, tender hepatomegaly, fever, weight
loss, abdominal discomfort

–Cirrhosis:
•similar to other causes of cirrhosis.
•Hepatomegaly, splenomegaly, malaise, jaundice, weight
loss, ascites, signs of CLD
Alcoholic Liver Disease and
Alcoholic Cirrhosis
•Hepatic steatosis;

–commonly referred to as fatty liver, is a frequent diagnosis that is not
exclusive to patients suffering from ALD.

–Fatty liver is the accumulation of triglycerides in the hepatocytes.

–Fatty liver has been demonstrated in 90% to 100% of all heavy drinkers.

–Short-term exposure to 80 g of alcohol (about 8 beers) over several days can
produce hepatic changes consistent with fatty liver disease.

–Fatty liver may develop after a single large binge and does not predict progression to
hepatitis
Alcohol and the Liver
•ALCOHOLIC FATTY LIVER:
–Fatty liver disease can be reversed if alcohol
consumption is stopped or significantly reduced.
–progression to fibrosis or cirrhosis occurred only in
patients who continued to ingest alcohol

–there are often no clinical symptoms, so fatty
liver may be undiagnosed. The only
complaint may be mild tender
hepatomegaly.

Alcohol and the Liver
•ALCOHOLIC FATTY LIVER:
•Pathology:
– macrovesicular fatty infiltration
–inflammatory changes are minimal
–fatty liver is not pathognomonic of ethanol ingestion:
• starvation,
•fatty liver of pregnancy,
•drug toxicity (valproic acid, tetracycline,
•antiviral agents such as zidovudine and dideoxyinosine),
•nonalcoholic steatohepatitis,
•viral hepatitis, particularly hepatitis C virus,
•Reye's syndrome,
•inborn errors of metabolism (such as defects in mitochondrial beta
oxidation)
Alcoholic Liver Disease and
Alcoholic Cirrhosis
•Alcoholic hepatitis
–fatty liver with the development of hepatitis, referred to as steatohepatitis, has
been acknowledged as a precursor for the development of cirrhosis.

–Alcoholic hepatitis results directly from alcohol abuse and is observed in as
many as 35% of heavy drinkers.

–Like other forms of hepatitis, alcoholic hepatitis can be subclinical.

–Laboratory findings are more predictive if the disease has progressed.

–Approximately 40% of patients with alcoholic hepatitis who continue to
drink will develop alcoholic cirrhosis within 1 to 2 years.
Alcohol and the Liver

•ALCOHOLIC HEPATITIS:

27. Alcohol and the Liver

Alcohol and the Liver
• There is a broad spectrum of clinical and
laboratory findings in patients with alcoholic
liver disease, ranging from asymptomatic
fatty liver to alcoholic hepatitis to end-stage
liver failure with jaundice, coagulopathy, and
encephalopathy
Loading…
Alcohol and the Liver
• FINDINGS IN ALCOHOLIC LIVER
DISEASE

–moderate alcohol intake appears to have
cardiovascular benefits

– excessive alcohol intake can be associated with
significant social and physical consequences

–for the development of cirrhosis:
•requirement for 80 grams of ethanol daily for 10 to 20
Alcohol and the liver

•In 2009, WHO listed alcohol use as one of the
leading causes of the global burden of
disease and injury, surpassed only slightly by
childhood malnourishment and unsafe sex.


•This placed alcohol use ahead of unsafe water
and sanitation, hypertension, high cholesterol,
and tobacco use, and clearly affirms that
alcohol is the most widely abused substance
Loading…
Alcoholism and the Effects of
Alcohol

•In the United States, approximately 100 000
deaths per year are attributed to alcohol abuse.

•Alcohol use is an underlying cause of more
than 30 conditions and a definite contributing
factor to many more, including
–psychotic disorder
–alcoholic cardiomyopathy
–amnesic syndrome
–alcoholic liver disease.
Alcoholism and the Effects of
Alcohol

•The Mayo Clinic defined alcoholism as a
chronic disease in which the body becomes
reliant upon alcohol (ethanol).

•Furthermore, it has been referred to as a
syndrome that consists of 2 phases:
–problem drinking
and
–alcohol addiction.

Alcoholic Liver Disease
•Beverage Alcohol

–Beer 5%

–Wine 12%

–Hard Liquor 40%
(Brandy, wisky, Rum)

–Arrack 40 – 50%
Alcoholism and the Effects of
Alcohol
•A standard alcoholic beverage has been described as any drink that
contains 14 g of pure alcohol.
•Irrespective of what form of alcohol is consumed, the greatest risk
factor appears to be the quantity of alcohol consumed.
•The definition for low-risk drinking for men and women differs,
because
–women suffer from hepatic damage and cirrhosis with considerably smaller
amounts of alcohol consumption.
–A man should not drink more than 4 drinks per day and no more than 14 drinks
per week.
–A woman should not drink more than 3 drinks per day and no more than 7 drinks
per week.
Risk for the development of ALD
Time to develop ALD = to amount of alcohol
consumed

•Men: 60-80 gm/day for 10 years

•Women: 20-40 gm/day for 10 years


Alcoholic cirrhosis, develops ONLY in 10 to 20% of
those who are chronically heavy drinkers.
Loading…
Risk for the development of ALD
•Epidemiology

–Over 90% of chronic heavy drinkers will develop
steatosis

–10 to 20% will develop alcoholic hepatitis

–ALD cause death of 1 in 50 people in Scotland

–4 fold increase in deaths from ALD in past 30
years
Risk for the development of ALD
•Risk of liver disease
–Amount of alcohol consumed
–Genetic factors
–Female sex
–Obesity
–Chronic viral hepatitis
–Nutritional impairment
–drugs
Alcohol Metabolism and the Liver
•The liver is the principal organ for alcohol metabolism.
•The body naturally recognizes ethanol alcohol as a foreign, toxic
agent that can disrupt normal homeostasis.
•When we consume ethanol, it is rapidly absorbed by the upper
gastrointestinal tract.
•Ethanol is
–diffused throughout the body, but exposure is greatest to the liver, via the
main portal vein.
–metabolized by the body in the gastric mucosa and the liver. These organs
manage an enzyme referred to as alcohol dehydrogenase, which is used by
the body to oxidize ethanol and convert it into acetaldehyde and other
metabolites.
–Acetaldehyde ultimately is converted by the body into acetic acid, and then
acetate. Acetaldehyde affects protein synthesis.
Alcohol Metabolism and the Liver


•Alcohol’s metabolites, especially acetaldehyde, damage vital liver
cells because of the excessive generation of free radicals.


•Excessive amount of this type of free radical causes oxidative
stress, which results in the body’s inability to prevent and repair
hepatic damage and the destruction of deoxyribonucleic acid.
Alcohol Metabolism and the Liver
•In addition to the immediate damage of acetaldehyde and the free
radicals, the phagocytic cells of the liver, the Kupffer cells, also
mount an immune response.
•This response is the result of an increase in toxins in the blood that
leak from the intestinal wall and enter the blood stream because of
alcohol consumption.
•The activation of Kupffer cells is responsible for early ethanol-
induced liver injury that ultimately leads to the death of
hepatocytes.
•This damage results in the manifestation of alcoholic liver disease,
and eventually to the development of fibrosis, or scar tissue, within
the liver.

Alcohol Metabolism and the Liver
•Alcohol metabolism differs dramatically between sexes.
–Women are much more likely to suffer from liver damage than men as a
result of alcohol consumption. However, this phenomenon is not clearly
understood.

•In addition to sex, the incidence of liver damage depends on the
– individual’s ethnicity
–genetic predisposition
–nutritional state.
Alcohol and the Liver
•Physical examination :

–vary from normal to evidence of cirrhosis or
hepatic decompensation
•Abdominal wall collaterals (caput medusa),
•Ascites,
•Cutaneous telangiectasias,
•Digital clubbing,
•Dupuytren's contractures,
•Gynecomastia,
•Jaundice,
•Malnutrition ,
•Palmar erythema,
•Peripheral neuropathy,
Alcohol and the Liver
•Laboratory findings:

–serum AST (SGOT), ALT (SGPT), and
gammaglutamyl transferase (GGT) are often
abnormal in alcoholic liver disease

–disproportionate elevation of serum AST (SGOT)
compared to ALT (SGPT) ratio is usually greater
than 2.0

–absolute values of serum AST and ALT are almost
always less than 500 IU/L
Alcohol and the Liver

–Consumption of alcohol can lead to a variety of
histopathologic changes in the liver ranging from
steatosis to cirrhosis
• Steatosis,
•alcoholic hepatitis,
•cirrhosis

–The mechanism behind the development of ALD is not
completely understood, because it is estimated that
only 10% to 20% of alcoholics develop cirrhosis.

Alcoholic Liver Disease
•Signs and symptoms
–Steatosis:
•usually asymptomatic, hepatomegaly

–Alcoholic hepatitis:
•malaise, jaundice, tender hepatomegaly, fever, weight
loss, abdominal discomfort

–Cirrhosis:
•similar to other causes of cirrhosis.
•Hepatomegaly, splenomegaly, malaise, jaundice, weight
loss, ascites, signs of CLD
Alcoholic Liver Disease and
Alcoholic Cirrhosis
•Hepatic steatosis;

–commonly referred to as fatty liver, is a frequent diagnosis that is not
exclusive to patients suffering from ALD.

–Fatty liver is the accumulation of triglycerides in the hepatocytes.

–Fatty liver has been demonstrated in 90% to 100% of all heavy drinkers.

–Short-term exposure to 80 g of alcohol (about 8 beers) over several days can
produce hepatic changes consistent with fatty liver disease.

–Fatty liver may develop after a single large binge and does not predict progression to
hepatitis
Alcohol and the Liver
•ALCOHOLIC FATTY LIVER:
–Fatty liver disease can be reversed if alcohol
consumption is stopped or significantly reduced.
–progression to fibrosis or cirrhosis occurred only in
patients who continued to ingest alcohol

–there are often no clinical symptoms, so fatty
liver may be undiagnosed. The only
complaint may be mild tender
hepatomegaly.

Alcohol and the Liver
•ALCOHOLIC FATTY LIVER:
•Pathology:
– macrovesicular fatty infiltration
–inflammatory changes are minimal
–fatty liver is not pathognomonic of ethanol ingestion:
• starvation,
•fatty liver of pregnancy,
•drug toxicity (valproic acid, tetracycline,
•antiviral agents such as zidovudine and dideoxyinosine),
•nonalcoholic steatohepatitis,
•viral hepatitis, particularly hepatitis C virus,
•Reye's syndrome,
•inborn errors of metabolism (such as defects in mitochondrial beta
oxidation)
Alcoholic Liver Disease and
Alcoholic Cirrhosis
•Alcoholic hepatitis
–fatty liver with the development of hepatitis, referred to as steatohepatitis, has
been acknowledged as a precursor for the development of cirrhosis.

–Alcoholic hepatitis results directly from alcohol abuse and is observed in as
many as 35% of heavy drinkers.

–Like other forms of hepatitis, alcoholic hepatitis can be subclinical.

–Laboratory findings are more predictive if the disease has progressed.

–Approximately 40% of patients with alcoholic hepatitis who continue to
drink will develop alcoholic cirrhosis within 1 to 2 years.
Alcohol and the Liver

•ALCOHOLIC HEPATITIS:

–Alcoholic hepatitis is defined by both clinical and
pathologic criteria

•clinically in a patient with a history of heavy alcohol use
and compatible clinical and laboratory findings

•clinical and laboratory features are often adequate for
establishing the diagnosis
Alcohol and the Liver

•ALCOHOLIC HEPATITIS:

–History is essential: information includes:

•amount and duration of alcohol ingestion,

•the possible presence of risk factors for hepatitis B or C

•use of potentially hepatotoxic drugs

•knowledge of prior liver disease.
Loading…
Alcohol and the Liver

•ALCOHOLIC HEPATITIS:

–Presentations
•Asymptomatic (majority of cases)
–Hepatomegaly
–Biochemistry mildly abnormal
–Needs histology for confirmation
•Symptomatic (minority of cases)
–Liver failure

– laboratory features:
Alcohol and the Liver
•ALCOHOLIC HEPATITIS:
–Clinical manifestations
•symptoms at presentation are those with fatty liver but
some patients remain asymptomatic.

•The characteristic signs and symptoms of alcoholic
hepatitis are
–Fever
–Hepatomegaly
–Jaundice
–anorexia
•The presence of stigmata of chronic liver disease (spider
angiomata, palmar erythema, gynecomastia) suggest
advanced disease with underlying cirrhosis.
Alcohol and the Liver
• ALCOHOLIC HEPATITIS: Pathology

–Obligatory features include
•Liver cell necrosis
•Mallory bodies
•Infiltration by neutrophils
•Perivenular distribution of inflammation

–not essential, histologic features include:
•bridging necrosis,
•fatty change,
•bile duct proliferation,
•cholestasis,
•perivenular fibrosis.
Alcoholic Liver Disease and
Alcoholic Cirrhosis

•alcoholic cirrhosis, is defined as a condition in which there is
continuing fibrosis resulting in the subdivision of the liver into
nodules of proliferating hepatocytes surrounded by scar tissue as
the direct result of chronic alcohol abuse.

•Alcoholic cirrhosis is a debilitating disease that remains among the
top 10 causes of death worldwide.
Alcoholic Liver Disease and
Alcoholic Cirrhosis

•Alcoholic cirrhosis is an irreversible condition that has an estimated
frequency of 10% to 15% among people who consume more than
50 g of alcohol daily over a 10-year period.

•It is characterized by both steatosis and hepatitis, and fibrosis. If left
unchecked and untreated, inflammation of the liver certainly
produces hepatic fibrosis.

•The principal pathogenic process in the development of cirrhosis is
the progressive fibrotic changes that occur within the liver
parenchyma combined with the disruption of the normal hepatic
vasculature.
Alcohol and the Liver
•CIRRHOSIS

–The clinical and laboratory features of alcoholic
cirrhosis are largely similar to those seen in other
causes of cirrhosis

–one exception: affected patients may have
concurrent evidence of alcoholic hepatitis.
• increased ratio of serum AST to ALT,
•jaundice, alkaline phosphatase elevation,
•hematologic abnormalities may coexist with stigmata of
chronic liver disease.

Alcohol and the Liver
• long-term management of alcoholic liver
disease:
– importance of abstinence
– well nourished, and nutritional supplements
–During hospitalizations for decompensation of
alcoholic liver disease, aggressive nutritional
therapy should be instituted
–Complications of cirrhosis that arise in patients
with alcoholic liver disease should be sought and
treated
–end stage alcoholic liver disease should be
considered for liver transplantation


•Young patient admitted to the emergency for
–Jaundice
–confusion

•Labs:
–ALT 2000
–AST 1500
–Total Bilirubin 20
•Direct: 15

•Next step ??

•Abdominal ultra sound

•Other labs test?

•Physical exam

Fulminant hepatic failure

Fulminant hepatic failure
definition

•Rapid development of severe acute liver injury
with impaired function and encephalopathy in
previously normal liver or well compensated
liver disease

–Encephalopathy within 8wks previous healthy
liver

–Encephalopathy within 2 wks of developing
jaundice with previous underlying liver
Subfulminant hepatic failure
definition

•FHF> 8wks – 6 months

•FHF VS sub FHF
–Cerebral edema is common in FHF and rare in sub
FHF
–Renal failure and portal hypertension are more
frequently with sub FHF

Causes of Acute liver failure

Viruses
Hepatitis A, B, C, D, E
Cytomegalovirus
Epstein–Barr virus
Herpes simplex virus 1 and 2
Varicella-zoster virus
Adenovirus
Dengue virus
Medications
Acetaminophen
Anti-tuberculosis (Isoniazid, Rifampin, Pyrazinamide)
Statins
Non-steroidal anti-inflammatory drugs
Sulfa drugs
Phenytoin
Carbamazepine
MDMA (ecstasy)
Flucloxacillin
Ketoconazole
Nitrofurantoin
Immune checkpoint inhibitors
Idiosyncratic drug reactions
Genetic/Autoimmune
Wilson disease
Autoimmune hepatitis
Vascular
Budd–Chiari syndrome
Veno-occlusive disease
Ischemic hepatitis
Herbals/Nutritional Supplements
Multiple agents (Kava Kava, Hydroxycut, Ma Huang, etc.)
Dietary and weight loss supplements
Multivitamins
Toxins
Mushroom (most commonly Amanita phalloides)
Carbon tetrachloride
Yellow phosphorus
Infiltration
Breast cancer
Small-cell lung cancer
Lymphoma
Colon cancer
Melanoma
Multiple myeloma
Pregnancy-related
Acute fatty liver of pregnancy
HELLP syndrome
Pre-eclamptic liver rupture
Other
Sepsis
Partial hepatectomy
Heat stroke
Hemophagocytic lymphohistiocytosis
causes
•Major causes of fulminant hepatic failure
–A- Acetaminophene, hep A, autoimmune hepatitis
–B- Hepatitis B
–C- Hepatitis C, cryptogenic
–D- Hepatitis D, drug
–E- Esoteric causes, Wilson’s disease, Budd-Chiari
–F – Fatty infiltration, acute fatty liver of
pregnancy, Reye’s syndrome

28. –Alcoholic hepatitis is defined by both clinical and
pathologic criteria

•clinically in a patient with a history of heavy alcohol use
and compatible clinical and laboratory findings

•clinical and laboratory features are often adequate for
establishing the diagnosis
Alcohol and the Liver

•ALCOHOLIC HEPATITIS:

–History is essential: information includes:

•amount and duration of alcohol ingestion,

•the possible presence of risk factors for hepatitis B or C

•use of potentially hepatotoxic drugs

•knowledge of prior liver disease.
Loading…
Alcohol and the Liver

•ALCOHOLIC HEPATITIS:

–Presentations
•Asymptomatic (majority of cases)
–Hepatomegaly
–Biochemistry mildly abnormal
–Needs histology for confirmation
•Symptomatic (minority of cases)
–Liver failure

– laboratory features:
Alcohol and the Liver
•ALCOHOLIC HEPATITIS:
–Clinical manifestations
•symptoms at presentation are those with fatty liver but
some patients remain asymptomatic.

•The characteristic signs and symptoms of alcoholic
hepatitis are
–Fever
–Hepatomegaly
–Jaundice
–anorexia
•The presence of stigmata of chronic liver disease (spider
angiomata, palmar erythema, gynecomastia) suggest
advanced disease with underlying cirrhosis.
Alcohol and the Liver
• ALCOHOLIC HEPATITIS: Pathology

–Obligatory features include
•Liver cell necrosis
•Mallory bodies
•Infiltration by neutrophils
•Perivenular distribution of inflammation

–not essential, histologic features include:
•bridging necrosis,
•fatty change,
•bile duct proliferation,
•cholestasis,
•perivenular fibrosis.
Alcoholic Liver Disease and
Alcoholic Cirrhosis

•alcoholic cirrhosis, is defined as a condition in which there is
continuing fibrosis resulting in the subdivision of the liver into
nodules of proliferating hepatocytes surrounded by scar tissue as
the direct result of chronic alcohol abuse.

•Alcoholic cirrhosis is a debilitating disease that remains among the
top 10 causes of death worldwide.
Alcoholic Liver Disease and
Alcoholic Cirrhosis

•Alcoholic cirrhosis is an irreversible condition that has an estimated
frequency of 10% to 15% among people who consume more than
50 g of alcohol daily over a 10-year period.

•It is characterized by both steatosis and hepatitis, and fibrosis. If left
unchecked and untreated, inflammation of the liver certainly
produces hepatic fibrosis.

•The principal pathogenic process in the development of cirrhosis is
the progressive fibrotic changes that occur within the liver
parenchyma combined with the disruption of the normal hepatic
vasculature.
Alcohol and the Liver
•CIRRHOSIS

–The clinical and laboratory features of alcoholic
cirrhosis are largely similar to those seen in other
causes of cirrhosis

–one exception: affected patients may have
concurrent evidence of alcoholic hepatitis.
• increased ratio of serum AST to ALT,
•jaundice, alkaline phosphatase elevation,
•hematologic abnormalities may coexist with stigmata of
chronic liver disease.

Alcohol and the Liver
• long-term management of alcoholic liver
disease:
– importance of abstinence
– well nourished, and nutritional supplements
–During hospitalizations for decompensation of
alcoholic liver disease, aggressive nutritional
therapy should be instituted
–Complications of cirrhosis that arise in patients
with alcoholic liver disease should be sought and
treated
–end stage alcoholic liver disease should be
considered for liver transplantation


•Young patient admitted to the emergency for
–Jaundice
–confusion

•Labs:
–ALT 2000
–AST 1500
–Total Bilirubin 20
•Direct: 15

•Next step ??

•Abdominal ultra sound

•Other labs test?

•Physical exam

Fulminant hepatic failure

Fulminant hepatic failure
definition

•Rapid development of severe acute liver injury
with impaired function and encephalopathy in
previously normal liver or well compensated
liver disease

–Encephalopathy within 8wks previous healthy
liver

–Encephalopathy within 2 wks of developing
jaundice with previous underlying liver
Subfulminant hepatic failure
definition

•FHF> 8wks – 6 months

•FHF VS sub FHF
–Cerebral edema is common in FHF and rare in sub
FHF
–Renal failure and portal hypertension are more
frequently with sub FHF

Causes of Acute liver failure

Viruses
Hepatitis A, B, C, D, E
Cytomegalovirus
Epstein–Barr virus
Herpes simplex virus 1 and 2
Varicella-zoster virus
Adenovirus
Dengue virus
Medications
Acetaminophen
Anti-tuberculosis (Isoniazid, Rifampin, Pyrazinamide)
Statins
Non-steroidal anti-inflammatory drugs
Sulfa drugs
Phenytoin
Carbamazepine
MDMA (ecstasy)
Flucloxacillin
Ketoconazole
Nitrofurantoin
Immune checkpoint inhibitors
Idiosyncratic drug reactions
Genetic/Autoimmune
Wilson disease
Autoimmune hepatitis
Vascular
Budd–Chiari syndrome
Veno-occlusive disease
Ischemic hepatitis
Herbals/Nutritional Supplements
Multiple agents (Kava Kava, Hydroxycut, Ma Huang, etc.)
Dietary and weight loss supplements
Multivitamins
Toxins
Mushroom (most commonly Amanita phalloides)
Carbon tetrachloride
Yellow phosphorus
Infiltration
Breast cancer
Small-cell lung cancer
Lymphoma
Colon cancer
Melanoma
Multiple myeloma
Pregnancy-related
Acute fatty liver of pregnancy
HELLP syndrome
Pre-eclamptic liver rupture
Other
Sepsis
Partial hepatectomy
Heat stroke
Hemophagocytic lymphohistiocytosis
causes
•Major causes of fulminant hepatic failure
–A- Acetaminophene, hep A, autoimmune hepatitis
–B- Hepatitis B
–C- Hepatitis C, cryptogenic
–D- Hepatitis D, drug
–E- Esoteric causes, Wilson’s disease, Budd-Chiari
–F – Fatty infiltration, acute fatty liver of
pregnancy, Reye’s syndrome

29. –Alcoholic hepatitis is defined by both clinical and
pathologic criteria

•clinically in a patient with a history of heavy alcohol use
and compatible clinical and laboratory findings

•clinical and laboratory features are often adequate for
establishing the diagnosis
Alcohol and the Liver

•ALCOHOLIC HEPATITIS:

–History is essential: information includes:

•amount and duration of alcohol ingestion,

•the possible presence of risk factors for hepatitis B or C

•use of potentially hepatotoxic drugs

•knowledge of prior liver disease.
Loading…
Alcohol and the Liver

•ALCOHOLIC HEPATITIS:

–Presentations
•Asymptomatic (majority of cases)
–Hepatomegaly
–Biochemistry mildly abnormal
–Needs histology for confirmation
•Symptomatic (minority of cases)
–Liver failure

– laboratory features:
Alcohol and the Liver
•ALCOHOLIC HEPATITIS:
–Clinical manifestations
•symptoms at presentation are those with fatty liver but
some patients remain asymptomatic.

•The characteristic signs and symptoms of alcoholic
hepatitis are
–Fever
–Hepatomegaly
–Jaundice
–anorexia
•The presence of stigmata of chronic liver disease (spider
angiomata, palmar erythema, gynecomastia) suggest
advanced disease with underlying cirrhosis.
Alcohol and the Liver
• ALCOHOLIC HEPATITIS: Pathology

–Obligatory features include
•Liver cell necrosis
•Mallory bodies
•Infiltration by neutrophils
•Perivenular distribution of inflammation

–not essential, histologic features include:
•bridging necrosis,
•fatty change,
•bile duct proliferation,
•cholestasis,
•perivenular fibrosis.
Alcoholic Liver Disease and
Alcoholic Cirrhosis

•alcoholic cirrhosis, is defined as a condition in which there is
continuing fibrosis resulting in the subdivision of the liver into
nodules of proliferating hepatocytes surrounded by scar tissue as
the direct result of chronic alcohol abuse.

•Alcoholic cirrhosis is a debilitating disease that remains among the
top 10 causes of death worldwide.
Alcoholic Liver Disease and
Alcoholic Cirrhosis

•Alcoholic cirrhosis is an irreversible condition that has an estimated
frequency of 10% to 15% among people who consume more than
50 g of alcohol daily over a 10-year period.

•It is characterized by both steatosis and hepatitis, and fibrosis. If left
unchecked and untreated, inflammation of the liver certainly
produces hepatic fibrosis.

•The principal pathogenic process in the development of cirrhosis is
the progressive fibrotic changes that occur within the liver
parenchyma combined with the disruption of the normal hepatic
vasculature.
Alcohol and the Liver
•CIRRHOSIS

–The clinical and laboratory features of alcoholic
cirrhosis are largely similar to those seen in other
causes of cirrhosis

–one exception: affected patients may have
concurrent evidence of alcoholic hepatitis.
• increased ratio of serum AST to ALT,
•jaundice, alkaline phosphatase elevation,
•hematologic abnormalities may coexist with stigmata of
chronic liver disease.

Alcohol and the Liver
• long-term management of alcoholic liver
disease:
– importance of abstinence
– well nourished, and nutritional supplements
–During hospitalizations for decompensation of
alcoholic liver disease, aggressive nutritional
therapy should be instituted
–Complications of cirrhosis that arise in patients
with alcoholic liver disease should be sought and
treated
–end stage alcoholic liver disease should be
considered for liver transplantation


•Young patient admitted to the emergency for
–Jaundice
–confusion

•Labs:
–ALT 2000
–AST 1500
–Total Bilirubin 20
•Direct: 15

•Next step ??

•Abdominal ultra sound

•Other labs test?

•Physical exam

Fulminant hepatic failure

Fulminant hepatic failure
definition

•Rapid development of severe acute liver injury
with impaired function and encephalopathy in
previously normal liver or well compensated
liver disease

–Encephalopathy within 8wks previous healthy
liver

–Encephalopathy within 2 wks of developing
jaundice with previous underlying liver
Subfulminant hepatic failure
definition

•FHF> 8wks – 6 months

•FHF VS sub FHF
–Cerebral edema is common in FHF and rare in sub
FHF
–Renal failure and portal hypertension are more
frequently with sub FHF

Causes of Acute liver failure

Viruses
Hepatitis A, B, C, D, E
Cytomegalovirus
Epstein–Barr virus
Herpes simplex virus 1 and 2
Varicella-zoster virus
Adenovirus
Dengue virus
Medications
Acetaminophen
Anti-tuberculosis (Isoniazid, Rifampin, Pyrazinamide)
Statins
Non-steroidal anti-inflammatory drugs
Sulfa drugs
Phenytoin
Carbamazepine
MDMA (ecstasy)
Flucloxacillin
Ketoconazole
Nitrofurantoin
Immune checkpoint inhibitors
Idiosyncratic drug reactions
Genetic/Autoimmune
Wilson disease
Autoimmune hepatitis
Vascular
Budd–Chiari syndrome
Veno-occlusive disease
Ischemic hepatitis
Herbals/Nutritional Supplements
Multiple agents (Kava Kava, Hydroxycut, Ma Huang, etc.)
Dietary and weight loss supplements
Multivitamins
Toxins
Mushroom (most commonly Amanita phalloides)
Carbon tetrachloride
Yellow phosphorus
Infiltration
Breast cancer
Small-cell lung cancer
Lymphoma
Colon cancer
Melanoma
Multiple myeloma
Pregnancy-related
Acute fatty liver of pregnancy
HELLP syndrome
Pre-eclamptic liver rupture
Other
Sepsis
Partial hepatectomy
Heat stroke
Hemophagocytic lymphohistiocytosis
causes
•Major causes of fulminant hepatic failure
–A- Acetaminophene, hep A, autoimmune hepatitis
–B- Hepatitis B
–C- Hepatitis C, cryptogenic
–D- Hepatitis D, drug
–E- Esoteric causes, Wilson’s disease, Budd-Chiari
–F – Fatty infiltration, acute fatty liver of
pregnancy, Reye’s syndrome

30. –Alcoholic hepatitis is defined by both clinical and
pathologic criteria

•clinically in a patient with a history of heavy alcohol use
and compatible clinical and laboratory findings

•clinical and laboratory features are often adequate for
establishing the diagnosis
Alcohol and the Liver

•ALCOHOLIC HEPATITIS:

–History is essential: information includes:

•amount and duration of alcohol ingestion,

•the possible presence of risk factors for hepatitis B or C

•use of potentially hepatotoxic drugs

•knowledge of prior liver disease.
Loading…
Alcohol and the Liver

•ALCOHOLIC HEPATITIS:

–Presentations
•Asymptomatic (majority of cases)
–Hepatomegaly
–Biochemistry mildly abnormal
–Needs histology for confirmation
•Symptomatic (minority of cases)
–Liver failure

– laboratory features:
Alcohol and the Liver
•ALCOHOLIC HEPATITIS:
–Clinical manifestations
•symptoms at presentation are those with fatty liver but
some patients remain asymptomatic.

•The characteristic signs and symptoms of alcoholic
hepatitis are
–Fever
–Hepatomegaly
–Jaundice
–anorexia
•The presence of stigmata of chronic liver disease (spider
angiomata, palmar erythema, gynecomastia) suggest
advanced disease with underlying cirrhosis.
Alcohol and the Liver
• ALCOHOLIC HEPATITIS: Pathology

–Obligatory features include
•Liver cell necrosis
•Mallory bodies
•Infiltration by neutrophils
•Perivenular distribution of inflammation

–not essential, histologic features include:
•bridging necrosis,
•fatty change,
•bile duct proliferation,
•cholestasis,
•perivenular fibrosis.
Alcoholic Liver Disease and
Alcoholic Cirrhosis

•alcoholic cirrhosis, is defined as a condition in which there is
continuing fibrosis resulting in the subdivision of the liver into
nodules of proliferating hepatocytes surrounded by scar tissue as
the direct result of chronic alcohol abuse.

•Alcoholic cirrhosis is a debilitating disease that remains among the
top 10 causes of death worldwide.
Alcoholic Liver Disease and
Alcoholic Cirrhosis

•Alcoholic cirrhosis is an irreversible condition that has an estimated
frequency of 10% to 15% among people who consume more than
50 g of alcohol daily over a 10-year period.

•It is characterized by both steatosis and hepatitis, and fibrosis. If left
unchecked and untreated, inflammation of the liver certainly
produces hepatic fibrosis.

•The principal pathogenic process in the development of cirrhosis is
the progressive fibrotic changes that occur within the liver
parenchyma combined with the disruption of the normal hepatic
vasculature.
Alcohol and the Liver
•CIRRHOSIS

–The clinical and laboratory features of alcoholic
cirrhosis are largely similar to those seen in other
causes of cirrhosis

–one exception: affected patients may have
concurrent evidence of alcoholic hepatitis.
• increased ratio of serum AST to ALT,
•jaundice, alkaline phosphatase elevation,
•hematologic abnormalities may coexist with stigmata of
chronic liver disease.

Alcohol and the Liver
• long-term management of alcoholic liver
disease:
– importance of abstinence
– well nourished, and nutritional supplements
–During hospitalizations for decompensation of
alcoholic liver disease, aggressive nutritional
therapy should be instituted
–Complications of cirrhosis that arise in patients
with alcoholic liver disease should be sought and
treated
–end stage alcoholic liver disease should be
considered for liver transplantation


•Young patient admitted to the emergency for
–Jaundice
–confusion

•Labs:
–ALT 2000
–AST 1500
–Total Bilirubin 20
•Direct: 15

•Next step ??

•Abdominal ultra sound

•Other labs test?

•Physical exam

Fulminant hepatic failure

Fulminant hepatic failure
definition

•Rapid development of severe acute liver injury
with impaired function and encephalopathy in
previously normal liver or well compensated
liver disease

–Encephalopathy within 8wks previous healthy
liver

–Encephalopathy within 2 wks of developing
jaundice with previous underlying liver
Subfulminant hepatic failure
definition

•FHF> 8wks – 6 months

•FHF VS sub FHF
–Cerebral edema is common in FHF and rare in sub
FHF
–Renal failure and portal hypertension are more
frequently with sub FHF

Causes of Acute liver failure

Viruses
Hepatitis A, B, C, D, E
Cytomegalovirus
Epstein–Barr virus
Herpes simplex virus 1 and 2
Varicella-zoster virus
Adenovirus
Dengue virus
Medications
Acetaminophen
Anti-tuberculosis (Isoniazid, Rifampin, Pyrazinamide)
Statins
Non-steroidal anti-inflammatory drugs
Sulfa drugs
Phenytoin
Carbamazepine
MDMA (ecstasy)
Flucloxacillin
Ketoconazole
Nitrofurantoin
Immune checkpoint inhibitors
Idiosyncratic drug reactions
Genetic/Autoimmune
Wilson disease
Autoimmune hepatitis
Vascular
Budd–Chiari syndrome
Veno-occlusive disease
Ischemic hepatitis
Herbals/Nutritional Supplements
Multiple agents (Kava Kava, Hydroxycut, Ma Huang, etc.)
Dietary and weight loss supplements
Multivitamins
Toxins
Mushroom (most commonly Amanita phalloides)
Carbon tetrachloride
Yellow phosphorus
Infiltration
Breast cancer
Small-cell lung cancer
Lymphoma
Colon cancer
Melanoma
Multiple myeloma
Pregnancy-related
Acute fatty liver of pregnancy
HELLP syndrome
Pre-eclamptic liver rupture
Other
Sepsis
Partial hepatectomy
Heat stroke
Hemophagocytic lymphohistiocytosis
causes
•Major causes of fulminant hepatic failure
–A- Acetaminophene, hep A, autoimmune hepatitis
–B- Hepatitis B
–C- Hepatitis C, cryptogenic
–D- Hepatitis D, drug
–E- Esoteric causes, Wilson’s disease, Budd-Chiari
–F – Fatty infiltration, acute fatty liver of
pregnancy, Reye’s syndrome

31. –Alcoholic hepatitis is defined by both clinical and
pathologic criteria

•clinically in a patient with a history of heavy alcohol use
and compatible clinical and laboratory findings

•clinical and laboratory features are often adequate for
establishing the diagnosis
Alcohol and the Liver

•ALCOHOLIC HEPATITIS:

–History is essential: information includes:

•amount and duration of alcohol ingestion,

•the possible presence of risk factors for hepatitis B or C

•use of potentially hepatotoxic drugs

•knowledge of prior liver disease.
Loading…
Alcohol and the Liver

•ALCOHOLIC HEPATITIS:

–Presentations
•Asymptomatic (majority of cases)
–Hepatomegaly
–Biochemistry mildly abnormal
–Needs histology for confirmation
•Symptomatic (minority of cases)
–Liver failure

– laboratory features:
Alcohol and the Liver
•ALCOHOLIC HEPATITIS:
–Clinical manifestations
•symptoms at presentation are those with fatty liver but
some patients remain asymptomatic.

•The characteristic signs and symptoms of alcoholic
hepatitis are
–Fever
–Hepatomegaly
–Jaundice
–anorexia
•The presence of stigmata of chronic liver disease (spider
angiomata, palmar erythema, gynecomastia) suggest
advanced disease with underlying cirrhosis.
Alcohol and the Liver
• ALCOHOLIC HEPATITIS: Pathology

–Obligatory features include
•Liver cell necrosis
•Mallory bodies
•Infiltration by neutrophils
•Perivenular distribution of inflammation

–not essential, histologic features include:
•bridging necrosis,
•fatty change,
•bile duct proliferation,
•cholestasis,
•perivenular fibrosis.
Alcoholic Liver Disease and
Alcoholic Cirrhosis

•alcoholic cirrhosis, is defined as a condition in which there is
continuing fibrosis resulting in the subdivision of the liver into
nodules of proliferating hepatocytes surrounded by scar tissue as
the direct result of chronic alcohol abuse.

•Alcoholic cirrhosis is a debilitating disease that remains among the
top 10 causes of death worldwide.
Alcoholic Liver Disease and
Alcoholic Cirrhosis

•Alcoholic cirrhosis is an irreversible condition that has an estimated
frequency of 10% to 15% among people who consume more than
50 g of alcohol daily over a 10-year period.

•It is characterized by both steatosis and hepatitis, and fibrosis. If left
unchecked and untreated, inflammation of the liver certainly
produces hepatic fibrosis.

•The principal pathogenic process in the development of cirrhosis is
the progressive fibrotic changes that occur within the liver
parenchyma combined with the disruption of the normal hepatic
vasculature.
Alcohol and the Liver
•CIRRHOSIS

–The clinical and laboratory features of alcoholic
cirrhosis are largely similar to those seen in other
causes of cirrhosis

–one exception: affected patients may have
concurrent evidence of alcoholic hepatitis.
• increased ratio of serum AST to ALT,
•jaundice, alkaline phosphatase elevation,
•hematologic abnormalities may coexist with stigmata of
chronic liver disease.

Alcohol and the Liver
• long-term management of alcoholic liver
disease:
– importance of abstinence
– well nourished, and nutritional supplements
–During hospitalizations for decompensation of
alcoholic liver disease, aggressive nutritional
therapy should be instituted
–Complications of cirrhosis that arise in patients
with alcoholic liver disease should be sought and
treated
–end stage alcoholic liver disease should be
considered for liver transplantation


•Young patient admitted to the emergency for
–Jaundice
–confusion

•Labs:
–ALT 2000
–AST 1500
–Total Bilirubin 20
•Direct: 15

•Next step ??

•Abdominal ultra sound

•Other labs test?

•Physical exam

Fulminant hepatic failure

Fulminant hepatic failure
definition

•Rapid development of severe acute liver injury
with impaired function and encephalopathy in
previously normal liver or well compensated
liver disease

–Encephalopathy within 8wks previous healthy
liver

–Encephalopathy within 2 wks of developing
jaundice with previous underlying liver
Subfulminant hepatic failure
definition

•FHF> 8wks – 6 months

•FHF VS sub FHF
–Cerebral edema is common in FHF and rare in sub
FHF
–Renal failure and portal hypertension are more
frequently with sub FHF

Causes of Acute liver failure

Viruses
Hepatitis A, B, C, D, E
Cytomegalovirus
Epstein–Barr virus
Herpes simplex virus 1 and 2
Varicella-zoster virus
Adenovirus
Dengue virus
Medications
Acetaminophen
Anti-tuberculosis (Isoniazid, Rifampin, Pyrazinamide)
Statins
Non-steroidal anti-inflammatory drugs
Sulfa drugs
Phenytoin
Carbamazepine
MDMA (ecstasy)
Flucloxacillin
Ketoconazole
Nitrofurantoin
Immune checkpoint inhibitors
Idiosyncratic drug reactions
Genetic/Autoimmune
Wilson disease
Autoimmune hepatitis
Vascular
Budd–Chiari syndrome
Veno-occlusive disease
Ischemic hepatitis
Herbals/Nutritional Supplements
Multiple agents (Kava Kava, Hydroxycut, Ma Huang, etc.)
Dietary and weight loss supplements
Multivitamins
Toxins
Mushroom (most commonly Amanita phalloides)
Carbon tetrachloride
Yellow phosphorus
Infiltration
Breast cancer
Small-cell lung cancer
Lymphoma
Colon cancer
Melanoma
Multiple myeloma
Pregnancy-related
Acute fatty liver of pregnancy
HELLP syndrome
Pre-eclamptic liver rupture
Other
Sepsis
Partial hepatectomy
Heat stroke
Hemophagocytic lymphohistiocytosis
causes
•Major causes of fulminant hepatic failure
–A- Acetaminophene, hep A, autoimmune hepatitis
–B- Hepatitis B
–C- Hepatitis C, cryptogenic
–D- Hepatitis D, drug
–E- Esoteric causes, Wilson’s disease, Budd-Chiari
–F – Fatty infiltration, acute fatty liver of
pregnancy, Reye’s syndrome

32. –Alcoholic hepatitis is defined by both clinical and
pathologic criteria

•clinically in a patient with a history of heavy alcohol use
and compatible clinical and laboratory findings

•clinical and laboratory features are often adequate for
establishing the diagnosis
Alcohol and the Liver

•ALCOHOLIC HEPATITIS:

–History is essential: information includes:

•amount and duration of alcohol ingestion,

•the possible presence of risk factors for hepatitis B or C

•use of potentially hepatotoxic drugs

•knowledge of prior liver disease.
Loading…
Alcohol and the Liver

•ALCOHOLIC HEPATITIS:

–Presentations
•Asymptomatic (majority of cases)
–Hepatomegaly
–Biochemistry mildly abnormal
–Needs histology for confirmation
•Symptomatic (minority of cases)
–Liver failure

– laboratory features:
Alcohol and the Liver
•ALCOHOLIC HEPATITIS:
–Clinical manifestations
•symptoms at presentation are those with fatty liver but
some patients remain asymptomatic.

•The characteristic signs and symptoms of alcoholic
hepatitis are
–Fever
–Hepatomegaly
–Jaundice
–anorexia
•The presence of stigmata of chronic liver disease (spider
angiomata, palmar erythema, gynecomastia) suggest
advanced disease with underlying cirrhosis.
Alcohol and the Liver
• ALCOHOLIC HEPATITIS: Pathology

–Obligatory features include
•Liver cell necrosis
•Mallory bodies
•Infiltration by neutrophils
•Perivenular distribution of inflammation

–not essential, histologic features include:
•bridging necrosis,
•fatty change,
•bile duct proliferation,
•cholestasis,
•perivenular fibrosis.
Alcoholic Liver Disease and
Alcoholic Cirrhosis

•alcoholic cirrhosis, is defined as a condition in which there is
continuing fibrosis resulting in the subdivision of the liver into
nodules of proliferating hepatocytes surrounded by scar tissue as
the direct result of chronic alcohol abuse.

•Alcoholic cirrhosis is a debilitating disease that remains among the
top 10 causes of death worldwide.
Alcoholic Liver Disease and
Alcoholic Cirrhosis

•Alcoholic cirrhosis is an irreversible condition that has an estimated
frequency of 10% to 15% among people who consume more than
50 g of alcohol daily over a 10-year period.

•It is characterized by both steatosis and hepatitis, and fibrosis. If left
unchecked and untreated, inflammation of the liver certainly
produces hepatic fibrosis.

•The principal pathogenic process in the development of cirrhosis is
the progressive fibrotic changes that occur within the liver
parenchyma combined with the disruption of the normal hepatic
vasculature.
Alcohol and the Liver
•CIRRHOSIS

–The clinical and laboratory features of alcoholic
cirrhosis are largely similar to those seen in other
causes of cirrhosis

–one exception: affected patients may have
concurrent evidence of alcoholic hepatitis.
• increased ratio of serum AST to ALT,
•jaundice, alkaline phosphatase elevation,
•hematologic abnormalities may coexist with stigmata of
chronic liver disease.

Alcohol and the Liver
• long-term management of alcoholic liver
disease:
– importance of abstinence
– well nourished, and nutritional supplements
–During hospitalizations for decompensation of
alcoholic liver disease, aggressive nutritional
therapy should be instituted
–Complications of cirrhosis that arise in patients
with alcoholic liver disease should be sought and
treated
–end stage alcoholic liver disease should be
considered for liver transplantation


•Young patient admitted to the emergency for
–Jaundice
–confusion

•Labs:
–ALT 2000
–AST 1500
–Total Bilirubin 20
•Direct: 15

•Next step ??

•Abdominal ultra sound

•Other labs test?

•Physical exam

Fulminant hepatic failure

Fulminant hepatic failure
definition

•Rapid development of severe acute liver injury
with impaired function and encephalopathy in
previously normal liver or well compensated
liver disease

–Encephalopathy within 8wks previous healthy
liver

–Encephalopathy within 2 wks of developing
jaundice with previous underlying liver
Subfulminant hepatic failure
definition

•FHF> 8wks – 6 months

•FHF VS sub FHF
–Cerebral edema is common in FHF and rare in sub
FHF
–Renal failure and portal hypertension are more
frequently with sub FHF

Causes of Acute liver failure

Viruses
Hepatitis A, B, C, D, E
Cytomegalovirus
Epstein–Barr virus
Herpes simplex virus 1 and 2
Varicella-zoster virus
Adenovirus
Dengue virus
Medications
Acetaminophen
Anti-tuberculosis (Isoniazid, Rifampin, Pyrazinamide)
Statins
Non-steroidal anti-inflammatory drugs
Sulfa drugs
Phenytoin
Carbamazepine
MDMA (ecstasy)
Flucloxacillin
Ketoconazole
Nitrofurantoin
Immune checkpoint inhibitors
Idiosyncratic drug reactions
Genetic/Autoimmune
Wilson disease
Autoimmune hepatitis
Vascular
Budd–Chiari syndrome
Veno-occlusive disease
Ischemic hepatitis
Herbals/Nutritional Supplements
Multiple agents (Kava Kava, Hydroxycut, Ma Huang, etc.)
Dietary and weight loss supplements
Multivitamins
Toxins
Mushroom (most commonly Amanita phalloides)
Carbon tetrachloride
Yellow phosphorus
Infiltration
Breast cancer
Small-cell lung cancer
Lymphoma
Colon cancer
Melanoma
Multiple myeloma
Pregnancy-related
Acute fatty liver of pregnancy
HELLP syndrome
Pre-eclamptic liver rupture
Other
Sepsis
Partial hepatectomy
Heat stroke
Hemophagocytic lymphohistiocytosis
causes
•Major causes of fulminant hepatic failure
–A- Acetaminophene, hep A, autoimmune hepatitis
–B- Hepatitis B
–C- Hepatitis C, cryptogenic
–D- Hepatitis D, drug
–E- Esoteric causes, Wilson’s disease, Budd-Chiari
–F – Fatty infiltration, acute fatty liver of
pregnancy, Reye’s syndrome

33. –Alcoholic hepatitis is defined by both clinical and
pathologic criteria

•clinically in a patient with a history of heavy alcohol use
and compatible clinical and laboratory findings

•clinical and laboratory features are often adequate for
establishing the diagnosis
Alcohol and the Liver

•ALCOHOLIC HEPATITIS:

–History is essential: information includes:

•amount and duration of alcohol ingestion,

•the possible presence of risk factors for hepatitis B or C

•use of potentially hepatotoxic drugs

•knowledge of prior liver disease.
Loading…
Alcohol and the Liver

•ALCOHOLIC HEPATITIS:

–Presentations
•Asymptomatic (majority of cases)
–Hepatomegaly
–Biochemistry mildly abnormal
–Needs histology for confirmation
•Symptomatic (minority of cases)
–Liver failure

– laboratory features:
Alcohol and the Liver
•ALCOHOLIC HEPATITIS:
–Clinical manifestations
•symptoms at presentation are those with fatty liver but
some patients remain asymptomatic.

•The characteristic signs and symptoms of alcoholic
hepatitis are
–Fever
–Hepatomegaly
–Jaundice
–anorexia
•The presence of stigmata of chronic liver disease (spider
angiomata, palmar erythema, gynecomastia) suggest
advanced disease with underlying cirrhosis.
Alcohol and the Liver
• ALCOHOLIC HEPATITIS: Pathology

–Obligatory features include
•Liver cell necrosis
•Mallory bodies
•Infiltration by neutrophils
•Perivenular distribution of inflammation

–not essential, histologic features include:
•bridging necrosis,
•fatty change,
•bile duct proliferation,
•cholestasis,
•perivenular fibrosis.
Alcoholic Liver Disease and
Alcoholic Cirrhosis

•alcoholic cirrhosis, is defined as a condition in which there is
continuing fibrosis resulting in the subdivision of the liver into
nodules of proliferating hepatocytes surrounded by scar tissue as
the direct result of chronic alcohol abuse.

•Alcoholic cirrhosis is a debilitating disease that remains among the
top 10 causes of death worldwide.
Alcoholic Liver Disease and
Alcoholic Cirrhosis

•Alcoholic cirrhosis is an irreversible condition that has an estimated
frequency of 10% to 15% among people who consume more than
50 g of alcohol daily over a 10-year period.

•It is characterized by both steatosis and hepatitis, and fibrosis. If left
unchecked and untreated, inflammation of the liver certainly
produces hepatic fibrosis.

•The principal pathogenic process in the development of cirrhosis is
the progressive fibrotic changes that occur within the liver
parenchyma combined with the disruption of the normal hepatic
vasculature.
Alcohol and the Liver
•CIRRHOSIS

–The clinical and laboratory features of alcoholic
cirrhosis are largely similar to those seen in other
causes of cirrhosis

–one exception: affected patients may have
concurrent evidence of alcoholic hepatitis.
• increased ratio of serum AST to ALT,
•jaundice, alkaline phosphatase elevation,
•hematologic abnormalities may coexist with stigmata of
chronic liver disease.

Alcohol and the Liver
• long-term management of alcoholic liver
disease:
– importance of abstinence
– well nourished, and nutritional supplements
–During hospitalizations for decompensation of
alcoholic liver disease, aggressive nutritional
therapy should be instituted
–Complications of cirrhosis that arise in patients
with alcoholic liver disease should be sought and
treated
–end stage alcoholic liver disease should be
considered for liver transplantation


•Young patient admitted to the emergency for
–Jaundice
–confusion

•Labs:
–ALT 2000
–AST 1500
–Total Bilirubin 20
•Direct: 15

•Next step ??

•Abdominal ultra sound

•Other labs test?

•Physical exam

Fulminant hepatic failure

Fulminant hepatic failure
definition

•Rapid development of severe acute liver injury
with impaired function and encephalopathy in
previously normal liver or well compensated
liver disease

–Encephalopathy within 8wks previous healthy
liver

–Encephalopathy within 2 wks of developing
jaundice with previous underlying liver
Subfulminant hepatic failure
definition

•FHF> 8wks – 6 months

•FHF VS sub FHF
–Cerebral edema is common in FHF and rare in sub
FHF
–Renal failure and portal hypertension are more
frequently with sub FHF

Causes of Acute liver failure

Viruses
Hepatitis A, B, C, D, E
Cytomegalovirus
Epstein–Barr virus
Herpes simplex virus 1 and 2
Varicella-zoster virus
Adenovirus
Dengue virus
Medications
Acetaminophen
Anti-tuberculosis (Isoniazid, Rifampin, Pyrazinamide)
Statins
Non-steroidal anti-inflammatory drugs
Sulfa drugs
Phenytoin
Carbamazepine
MDMA (ecstasy)
Flucloxacillin
Ketoconazole
Nitrofurantoin
Immune checkpoint inhibitors
Idiosyncratic drug reactions
Genetic/Autoimmune
Wilson disease
Autoimmune hepatitis
Vascular
Budd–Chiari syndrome
Veno-occlusive disease
Ischemic hepatitis
Herbals/Nutritional Supplements
Multiple agents (Kava Kava, Hydroxycut, Ma Huang, etc.)
Dietary and weight loss supplements
Multivitamins
Toxins
Mushroom (most commonly Amanita phalloides)
Carbon tetrachloride
Yellow phosphorus
Infiltration
Breast cancer
Small-cell lung cancer
Lymphoma
Colon cancer
Melanoma
Multiple myeloma
Pregnancy-related
Acute fatty liver of pregnancy
HELLP syndrome
Pre-eclamptic liver rupture
Other
Sepsis
Partial hepatectomy
Heat stroke
Hemophagocytic lymphohistiocytosis
causes
•Major causes of fulminant hepatic failure
–A- Acetaminophene, hep A, autoimmune hepatitis
–B- Hepatitis B
–C- Hepatitis C, cryptogenic
–D- Hepatitis D, drug
–E- Esoteric causes, Wilson’s disease, Budd-Chiari
–F – Fatty infiltration, acute fatty liver of
pregnancy, Reye’s syndrome

34. –Alcoholic hepatitis is defined by both clinical and
pathologic criteria

•clinically in a patient with a history of heavy alcohol use
and compatible clinical and laboratory findings

•clinical and laboratory features are often adequate for
establishing the diagnosis
Alcohol and the Liver

•ALCOHOLIC HEPATITIS:

–History is essential: information includes:

•amount and duration of alcohol ingestion,

•the possible presence of risk factors for hepatitis B or C

•use of potentially hepatotoxic drugs

•knowledge of prior liver disease.
Loading…
Alcohol and the Liver

•ALCOHOLIC HEPATITIS:

–Presentations
•Asymptomatic (majority of cases)
–Hepatomegaly
–Biochemistry mildly abnormal
–Needs histology for confirmation
•Symptomatic (minority of cases)
–Liver failure

– laboratory features:
Alcohol and the Liver
•ALCOHOLIC HEPATITIS:
–Clinical manifestations
•symptoms at presentation are those with fatty liver but
some patients remain asymptomatic.

•The characteristic signs and symptoms of alcoholic
hepatitis are
–Fever
–Hepatomegaly
–Jaundice
–anorexia
•The presence of stigmata of chronic liver disease (spider
angiomata, palmar erythema, gynecomastia) suggest
advanced disease with underlying cirrhosis.
Alcohol and the Liver
• ALCOHOLIC HEPATITIS: Pathology

–Obligatory features include
•Liver cell necrosis
•Mallory bodies
•Infiltration by neutrophils
•Perivenular distribution of inflammation

–not essential, histologic features include:
•bridging necrosis,
•fatty change,
•bile duct proliferation,
•cholestasis,
•perivenular fibrosis.
Alcoholic Liver Disease and
Alcoholic Cirrhosis

•alcoholic cirrhosis, is defined as a condition in which there is
continuing fibrosis resulting in the subdivision of the liver into
nodules of proliferating hepatocytes surrounded by scar tissue as
the direct result of chronic alcohol abuse.

•Alcoholic cirrhosis is a debilitating disease that remains among the
top 10 causes of death worldwide.
Alcoholic Liver Disease and
Alcoholic Cirrhosis

•Alcoholic cirrhosis is an irreversible condition that has an estimated
frequency of 10% to 15% among people who consume more than
50 g of alcohol daily over a 10-year period.

•It is characterized by both steatosis and hepatitis, and fibrosis. If left
unchecked and untreated, inflammation of the liver certainly
produces hepatic fibrosis.

•The principal pathogenic process in the development of cirrhosis is
the progressive fibrotic changes that occur within the liver
parenchyma combined with the disruption of the normal hepatic
vasculature.
Alcohol and the Liver
•CIRRHOSIS

–The clinical and laboratory features of alcoholic
cirrhosis are largely similar to those seen in other
causes of cirrhosis

–one exception: affected patients may have
concurrent evidence of alcoholic hepatitis.
• increased ratio of serum AST to ALT,
•jaundice, alkaline phosphatase elevation,
•hematologic abnormalities may coexist with stigmata of
chronic liver disease.

Alcohol and the Liver
• long-term management of alcoholic liver
disease:
– importance of abstinence
– well nourished, and nutritional supplements
–During hospitalizations for decompensation of
alcoholic liver disease, aggressive nutritional
therapy should be instituted
–Complications of cirrhosis that arise in patients
with alcoholic liver disease should be sought and
treated
–end stage alcoholic liver disease should be
considered for liver transplantation


•Young patient admitted to the emergency for
–Jaundice
–confusion

•Labs:
–ALT 2000
–AST 1500
–Total Bilirubin 20
•Direct: 15

•Next step ??

•Abdominal ultra sound

•Other labs test?

•Physical exam

Fulminant hepatic failure

Fulminant hepatic failure
definition

•Rapid development of severe acute liver injury
with impaired function and encephalopathy in
previously normal liver or well compensated
liver disease

–Encephalopathy within 8wks previous healthy
liver

–Encephalopathy within 2 wks of developing
jaundice with previous underlying liver
Subfulminant hepatic failure
definition

•FHF> 8wks – 6 months

•FHF VS sub FHF
–Cerebral edema is common in FHF and rare in sub
FHF
–Renal failure and portal hypertension are more
frequently with sub FHF

Causes of Acute liver failure

Viruses
Hepatitis A, B, C, D, E
Cytomegalovirus
Epstein–Barr virus
Herpes simplex virus 1 and 2
Varicella-zoster virus
Adenovirus
Dengue virus
Medications
Acetaminophen
Anti-tuberculosis (Isoniazid, Rifampin, Pyrazinamide)
Statins
Non-steroidal anti-inflammatory drugs
Sulfa drugs
Phenytoin
Carbamazepine
MDMA (ecstasy)
Flucloxacillin
Ketoconazole
Nitrofurantoin
Immune checkpoint inhibitors
Idiosyncratic drug reactions
Genetic/Autoimmune
Wilson disease
Autoimmune hepatitis
Vascular
Budd–Chiari syndrome
Veno-occlusive disease
Ischemic hepatitis
Herbals/Nutritional Supplements
Multiple agents (Kava Kava, Hydroxycut, Ma Huang, etc.)
Dietary and weight loss supplements
Multivitamins
Toxins
Mushroom (most commonly Amanita phalloides)
Carbon tetrachloride
Yellow phosphorus
Infiltration
Breast cancer
Small-cell lung cancer
Lymphoma
Colon cancer
Melanoma
Multiple myeloma
Pregnancy-related
Acute fatty liver of pregnancy
HELLP syndrome
Pre-eclamptic liver rupture
Other
Sepsis
Partial hepatectomy
Heat stroke
Hemophagocytic lymphohistiocytosis
causes
•Major causes of fulminant hepatic failure
–A- Acetaminophene, hep A, autoimmune hepatitis
–B- Hepatitis B
–C- Hepatitis C, cryptogenic
–D- Hepatitis D, drug
–E- Esoteric causes, Wilson’s disease, Budd-Chiari
–F – Fatty infiltration, acute fatty liver of
pregnancy, Reye’s syndrome

35. –Alcoholic hepatitis is defined by both clinical and
pathologic criteria

•clinically in a patient with a history of heavy alcohol use
and compatible clinical and laboratory findings

•clinical and laboratory features are often adequate for
establishing the diagnosis
Alcohol and the Liver

•ALCOHOLIC HEPATITIS:

–History is essential: information includes:

•amount and duration of alcohol ingestion,

•the possible presence of risk factors for hepatitis B or C

•use of potentially hepatotoxic drugs

•knowledge of prior liver disease.
Loading…
Alcohol and the Liver

•ALCOHOLIC HEPATITIS:

–Presentations
•Asymptomatic (majority of cases)
–Hepatomegaly
–Biochemistry mildly abnormal
–Needs histology for confirmation
•Symptomatic (minority of cases)
–Liver failure

– laboratory features:
Alcohol and the Liver
•ALCOHOLIC HEPATITIS:
–Clinical manifestations
•symptoms at presentation are those with fatty liver but
some patients remain asymptomatic.

•The characteristic signs and symptoms of alcoholic
hepatitis are
–Fever
–Hepatomegaly
–Jaundice
–anorexia
•The presence of stigmata of chronic liver disease (spider
angiomata, palmar erythema, gynecomastia) suggest
advanced disease with underlying cirrhosis.
Alcohol and the Liver
• ALCOHOLIC HEPATITIS: Pathology

–Obligatory features include
•Liver cell necrosis
•Mallory bodies
•Infiltration by neutrophils
•Perivenular distribution of inflammation

–not essential, histologic features include:
•bridging necrosis,
•fatty change,
•bile duct proliferation,
•cholestasis,
•perivenular fibrosis.
Alcoholic Liver Disease and
Alcoholic Cirrhosis

•alcoholic cirrhosis, is defined as a condition in which there is
continuing fibrosis resulting in the subdivision of the liver into
nodules of proliferating hepatocytes surrounded by scar tissue as
the direct result of chronic alcohol abuse.

•Alcoholic cirrhosis is a debilitating disease that remains among the
top 10 causes of death worldwide.
Alcoholic Liver Disease and
Alcoholic Cirrhosis

•Alcoholic cirrhosis is an irreversible condition that has an estimated
frequency of 10% to 15% among people who consume more than
50 g of alcohol daily over a 10-year period.

•It is characterized by both steatosis and hepatitis, and fibrosis. If left
unchecked and untreated, inflammation of the liver certainly
produces hepatic fibrosis.

•The principal pathogenic process in the development of cirrhosis is
the progressive fibrotic changes that occur within the liver
parenchyma combined with the disruption of the normal hepatic
vasculature.
Alcohol and the Liver
•CIRRHOSIS

–The clinical and laboratory features of alcoholic
cirrhosis are largely similar to those seen in other
causes of cirrhosis

–one exception: affected patients may have
concurrent evidence of alcoholic hepatitis.
• increased ratio of serum AST to ALT,
•jaundice, alkaline phosphatase elevation,
•hematologic abnormalities may coexist with stigmata of
chronic liver disease.

Alcohol and the Liver
• long-term management of alcoholic liver
disease:
– importance of abstinence
– well nourished, and nutritional supplements
–During hospitalizations for decompensation of
alcoholic liver disease, aggressive nutritional
therapy should be instituted
–Complications of cirrhosis that arise in patients
with alcoholic liver disease should be sought and
treated
–end stage alcoholic liver disease should be
considered for liver transplantation


•Young patient admitted to the emergency for
–Jaundice
–confusion

•Labs:
–ALT 2000
–AST 1500
–Total Bilirubin 20
•Direct: 15

•Next step ??

•Abdominal ultra sound

•Other labs test?

•Physical exam

Fulminant hepatic failure

Fulminant hepatic failure
definition

•Rapid development of severe acute liver injury
with impaired function and encephalopathy in
previously normal liver or well compensated
liver disease

–Encephalopathy within 8wks previous healthy
liver

–Encephalopathy within 2 wks of developing
jaundice with previous underlying liver
Subfulminant hepatic failure
definition

•FHF> 8wks – 6 months

•FHF VS sub FHF
–Cerebral edema is common in FHF and rare in sub
FHF
–Renal failure and portal hypertension are more
frequently with sub FHF

Causes of Acute liver failure

Viruses
Hepatitis A, B, C, D, E
Cytomegalovirus
Epstein–Barr virus
Herpes simplex virus 1 and 2
Varicella-zoster virus
Adenovirus
Dengue virus
Medications
Acetaminophen
Anti-tuberculosis (Isoniazid, Rifampin, Pyrazinamide)
Statins
Non-steroidal anti-inflammatory drugs
Sulfa drugs
Phenytoin
Carbamazepine
MDMA (ecstasy)
Flucloxacillin
Ketoconazole
Nitrofurantoin
Immune checkpoint inhibitors
Idiosyncratic drug reactions
Genetic/Autoimmune
Wilson disease
Autoimmune hepatitis
Vascular
Budd–Chiari syndrome
Veno-occlusive disease
Ischemic hepatitis
Herbals/Nutritional Supplements
Multiple agents (Kava Kava, Hydroxycut, Ma Huang, etc.)
Dietary and weight loss supplements
Multivitamins
Toxins
Mushroom (most commonly Amanita phalloides)
Carbon tetrachloride
Yellow phosphorus
Infiltration
Breast cancer
Small-cell lung cancer
Lymphoma
Colon cancer
Melanoma
Multiple myeloma
Pregnancy-related
Acute fatty liver of pregnancy
HELLP syndrome
Pre-eclamptic liver rupture
Other
Sepsis
Partial hepatectomy
Heat stroke
Hemophagocytic lymphohistiocytosis
causes
•Major causes of fulminant hepatic failure
–A- Acetaminophene, hep A, autoimmune hepatitis
–B- Hepatitis B
–C- Hepatitis C, cryptogenic
–D- Hepatitis D, drug
–E- Esoteric causes, Wilson’s disease, Budd-Chiari
–F – Fatty infiltration, acute fatty liver of
pregnancy, Reye’s syndrome

36. –Alcoholic hepatitis is defined by both clinical and
pathologic criteria

•clinically in a patient with a history of heavy alcohol use
and compatible clinical and laboratory findings

•clinical and laboratory features are often adequate for
establishing the diagnosis
Alcohol and the Liver

•ALCOHOLIC HEPATITIS:

–History is essential: information includes:

•amount and duration of alcohol ingestion,

•the possible presence of risk factors for hepatitis B or C

•use of potentially hepatotoxic drugs

•knowledge of prior liver disease.
Loading…
Alcohol and the Liver

•ALCOHOLIC HEPATITIS:

–Presentations
•Asymptomatic (majority of cases)
–Hepatomegaly
–Biochemistry mildly abnormal
–Needs histology for confirmation
•Symptomatic (minority of cases)
–Liver failure

– laboratory features:
Alcohol and the Liver
•ALCOHOLIC HEPATITIS:
–Clinical manifestations
•symptoms at presentation are those with fatty liver but
some patients remain asymptomatic.

•The characteristic signs and symptoms of alcoholic
hepatitis are
–Fever
–Hepatomegaly
–Jaundice
–anorexia
•The presence of stigmata of chronic liver disease (spider
angiomata, palmar erythema, gynecomastia) suggest
advanced disease with underlying cirrhosis.
Alcohol and the Liver
• ALCOHOLIC HEPATITIS: Pathology

–Obligatory features include
•Liver cell necrosis
•Mallory bodies
•Infiltration by neutrophils
•Perivenular distribution of inflammation

–not essential, histologic features include:
•bridging necrosis,
•fatty change,
•bile duct proliferation,
•cholestasis,
•perivenular fibrosis.
Alcoholic Liver Disease and
Alcoholic Cirrhosis

•alcoholic cirrhosis, is defined as a condition in which there is
continuing fibrosis resulting in the subdivision of the liver into
nodules of proliferating hepatocytes surrounded by scar tissue as
the direct result of chronic alcohol abuse.

•Alcoholic cirrhosis is a debilitating disease that remains among the
top 10 causes of death worldwide.
Alcoholic Liver Disease and
Alcoholic Cirrhosis

•Alcoholic cirrhosis is an irreversible condition that has an estimated
frequency of 10% to 15% among people who consume more than
50 g of alcohol daily over a 10-year period.

•It is characterized by both steatosis and hepatitis, and fibrosis. If left
unchecked and untreated, inflammation of the liver certainly
produces hepatic fibrosis.

•The principal pathogenic process in the development of cirrhosis is
the progressive fibrotic changes that occur within the liver
parenchyma combined with the disruption of the normal hepatic
vasculature.
Alcohol and the Liver
•CIRRHOSIS

–The clinical and laboratory features of alcoholic
cirrhosis are largely similar to those seen in other
causes of cirrhosis

–one exception: affected patients may have
concurrent evidence of alcoholic hepatitis.
• increased ratio of serum AST to ALT,
•jaundice, alkaline phosphatase elevation,
•hematologic abnormalities may coexist with stigmata of
chronic liver disease.

Alcohol and the Liver
• long-term management of alcoholic liver
disease:
– importance of abstinence
– well nourished, and nutritional supplements
–During hospitalizations for decompensation of
alcoholic liver disease, aggressive nutritional
therapy should be instituted
–Complications of cirrhosis that arise in patients
with alcoholic liver disease should be sought and
treated
–end stage alcoholic liver disease should be
considered for liver transplantation


•Young patient admitted to the emergency for
–Jaundice
–confusion

•Labs:
–ALT 2000
–AST 1500
–Total Bilirubin 20
•Direct: 15

•Next step ??

•Abdominal ultra sound

•Other labs test?

•Physical exam

Fulminant hepatic failure

Fulminant hepatic failure
definition

•Rapid development of severe acute liver injury
with impaired function and encephalopathy in
previously normal liver or well compensated
liver disease

–Encephalopathy within 8wks previous healthy
liver

–Encephalopathy within 2 wks of developing
jaundice with previous underlying liver
Subfulminant hepatic failure
definition

•FHF> 8wks – 6 months

•FHF VS sub FHF
–Cerebral edema is common in FHF and rare in sub
FHF
–Renal failure and portal hypertension are more
frequently with sub FHF

Causes of Acute liver failure

Viruses
Hepatitis A, B, C, D, E
Cytomegalovirus
Epstein–Barr virus
Herpes simplex virus 1 and 2
Varicella-zoster virus
Adenovirus
Dengue virus
Medications
Acetaminophen
Anti-tuberculosis (Isoniazid, Rifampin, Pyrazinamide)
Statins
Non-steroidal anti-inflammatory drugs
Sulfa drugs
Phenytoin
Carbamazepine
MDMA (ecstasy)
Flucloxacillin
Ketoconazole
Nitrofurantoin
Immune checkpoint inhibitors
Idiosyncratic drug reactions
Genetic/Autoimmune
Wilson disease
Autoimmune hepatitis
Vascular
Budd–Chiari syndrome
Veno-occlusive disease
Ischemic hepatitis
Herbals/Nutritional Supplements
Multiple agents (Kava Kava, Hydroxycut, Ma Huang, etc.)
Dietary and weight loss supplements
Multivitamins
Toxins
Mushroom (most commonly Amanita phalloides)
Carbon tetrachloride
Yellow phosphorus
Infiltration
Breast cancer
Small-cell lung cancer
Lymphoma
Colon cancer
Melanoma
Multiple myeloma
Pregnancy-related
Acute fatty liver of pregnancy
HELLP syndrome
Pre-eclamptic liver rupture
Other
Sepsis
Partial hepatectomy
Heat stroke
Hemophagocytic lymphohistiocytosis
causes
•Major causes of fulminant hepatic failure
–A- Acetaminophene, hep A, autoimmune hepatitis
–B- Hepatitis B
–C- Hepatitis C, cryptogenic
–D- Hepatitis D, drug
–E- Esoteric causes, Wilson’s disease, Budd-Chiari
–F – Fatty infiltration, acute fatty liver of
pregnancy, Reye’s syndrome

37. –Alcoholic hepatitis is defined by both clinical and
pathologic criteria

•clinically in a patient with a history of heavy alcohol use
and compatible clinical and laboratory findings

•clinical and laboratory features are often adequate for
establishing the diagnosis
Alcohol and the Liver

•ALCOHOLIC HEPATITIS:

–History is essential: information includes:

•amount and duration of alcohol ingestion,

•the possible presence of risk factors for hepatitis B or C

•use of potentially hepatotoxic drugs

•knowledge of prior liver disease.
Loading…
Alcohol and the Liver

•ALCOHOLIC HEPATITIS:

–Presentations
•Asymptomatic (majority of cases)
–Hepatomegaly
–Biochemistry mildly abnormal
–Needs histology for confirmation
•Symptomatic (minority of cases)
–Liver failure

– laboratory features:
Alcohol and the Liver
•ALCOHOLIC HEPATITIS:
–Clinical manifestations
•symptoms at presentation are those with fatty liver but
some patients remain asymptomatic.

•The characteristic signs and symptoms of alcoholic
hepatitis are
–Fever
–Hepatomegaly
–Jaundice
–anorexia
•The presence of stigmata of chronic liver disease (spider
angiomata, palmar erythema, gynecomastia) suggest
advanced disease with underlying cirrhosis.
Alcohol and the Liver
• ALCOHOLIC HEPATITIS: Pathology

–Obligatory features include
•Liver cell necrosis
•Mallory bodies
•Infiltration by neutrophils
•Perivenular distribution of inflammation

–not essential, histologic features include:
•bridging necrosis,
•fatty change,
•bile duct proliferation,
•cholestasis,
•perivenular fibrosis.
Alcoholic Liver Disease and
Alcoholic Cirrhosis

•alcoholic cirrhosis, is defined as a condition in which there is
continuing fibrosis resulting in the subdivision of the liver into
nodules of proliferating hepatocytes surrounded by scar tissue as
the direct result of chronic alcohol abuse.

•Alcoholic cirrhosis is a debilitating disease that remains among the
top 10 causes of death worldwide.
Alcoholic Liver Disease and
Alcoholic Cirrhosis

•Alcoholic cirrhosis is an irreversible condition that has an estimated
frequency of 10% to 15% among people who consume more than
50 g of alcohol daily over a 10-year period.

•It is characterized by both steatosis and hepatitis, and fibrosis. If left
unchecked and untreated, inflammation of the liver certainly
produces hepatic fibrosis.

•The principal pathogenic process in the development of cirrhosis is
the progressive fibrotic changes that occur within the liver
parenchyma combined with the disruption of the normal hepatic
vasculature.
Alcohol and the Liver
•CIRRHOSIS

–The clinical and laboratory features of alcoholic
cirrhosis are largely similar to those seen in other
causes of cirrhosis

–one exception: affected patients may have
concurrent evidence of alcoholic hepatitis.
• increased ratio of serum AST to ALT,
•jaundice, alkaline phosphatase elevation,
•hematologic abnormalities may coexist with stigmata of
chronic liver disease.

Alcohol and the Liver
• long-term management of alcoholic liver
disease:
– importance of abstinence
– well nourished, and nutritional supplements
–During hospitalizations for decompensation of
alcoholic liver disease, aggressive nutritional
therapy should be instituted
–Complications of cirrhosis that arise in patients
with alcoholic liver disease should be sought and
treated
–end stage alcoholic liver disease should be
considered for liver transplantation


•Young patient admitted to the emergency for
–Jaundice
–confusion

•Labs:
–ALT 2000
–AST 1500
–Total Bilirubin 20
•Direct: 15

•Next step ??

•Abdominal ultra sound

•Other labs test?

•Physical exam

Fulminant hepatic failure

Fulminant hepatic failure
definition

•Rapid development of severe acute liver injury
with impaired function and encephalopathy in
previously normal liver or well compensated
liver disease

–Encephalopathy within 8wks previous healthy
liver

–Encephalopathy within 2 wks of developing
jaundice with previous underlying liver
Subfulminant hepatic failure
definition

•FHF> 8wks – 6 months

•FHF VS sub FHF
–Cerebral edema is common in FHF and rare in sub
FHF
–Renal failure and portal hypertension are more
frequently with sub FHF

Causes of Acute liver failure

Viruses
Hepatitis A, B, C, D, E
Cytomegalovirus
Epstein–Barr virus
Herpes simplex virus 1 and 2
Varicella-zoster virus
Adenovirus
Dengue virus
Medications
Acetaminophen
Anti-tuberculosis (Isoniazid, Rifampin, Pyrazinamide)
Statins
Non-steroidal anti-inflammatory drugs
Sulfa drugs
Phenytoin
Carbamazepine
MDMA (ecstasy)
Flucloxacillin
Ketoconazole
Nitrofurantoin
Immune checkpoint inhibitors
Idiosyncratic drug reactions
Genetic/Autoimmune
Wilson disease
Autoimmune hepatitis
Vascular
Budd–Chiari syndrome
Veno-occlusive disease
Ischemic hepatitis
Herbals/Nutritional Supplements
Multiple agents (Kava Kava, Hydroxycut, Ma Huang, etc.)
Dietary and weight loss supplements
Multivitamins
Toxins
Mushroom (most commonly Amanita phalloides)
Carbon tetrachloride
Yellow phosphorus
Infiltration
Breast cancer
Small-cell lung cancer
Lymphoma
Colon cancer
Melanoma
Multiple myeloma
Pregnancy-related
Acute fatty liver of pregnancy
HELLP syndrome
Pre-eclamptic liver rupture
Other
Sepsis
Partial hepatectomy
Heat stroke
Hemophagocytic lymphohistiocytosis
causes
•Major causes of fulminant hepatic failure
–A- Acetaminophene, hep A, autoimmune hepatitis
–B- Hepatitis B
–C- Hepatitis C, cryptogenic
–D- Hepatitis D, drug
–E- Esoteric causes, Wilson’s disease, Budd-Chiari
–F – Fatty infiltration, acute fatty liver of
pregnancy, Reye’s syndrome

38. –Alcoholic hepatitis is defined by both clinical and
pathologic criteria

•clinically in a patient with a history of heavy alcohol use
and compatible clinical and laboratory findings

•clinical and laboratory features are often adequate for
establishing the diagnosis
Alcohol and the Liver

•ALCOHOLIC HEPATITIS:

–History is essential: information includes:

•amount and duration of alcohol ingestion,

•the possible presence of risk factors for hepatitis B or C

•use of potentially hepatotoxic drugs

•knowledge of prior liver disease.
Loading…
Alcohol and the Liver

•ALCOHOLIC HEPATITIS:

–Presentations
•Asymptomatic (majority of cases)
–Hepatomegaly
–Biochemistry mildly abnormal
–Needs histology for confirmation
•Symptomatic (minority of cases)
–Liver failure

– laboratory features:
Alcohol and the Liver
•ALCOHOLIC HEPATITIS:
–Clinical manifestations
•symptoms at presentation are those with fatty liver but
some patients remain asymptomatic.

•The characteristic signs and symptoms of alcoholic
hepatitis are
–Fever
–Hepatomegaly
–Jaundice
–anorexia
•The presence of stigmata of chronic liver disease (spider
angiomata, palmar erythema, gynecomastia) suggest
advanced disease with underlying cirrhosis.
Alcohol and the Liver
• ALCOHOLIC HEPATITIS: Pathology

–Obligatory features include
•Liver cell necrosis
•Mallory bodies
•Infiltration by neutrophils
•Perivenular distribution of inflammation

–not essential, histologic features include:
•bridging necrosis,
•fatty change,
•bile duct proliferation,
•cholestasis,
•perivenular fibrosis.
Alcoholic Liver Disease and
Alcoholic Cirrhosis

•alcoholic cirrhosis, is defined as a condition in which there is
continuing fibrosis resulting in the subdivision of the liver into
nodules of proliferating hepatocytes surrounded by scar tissue as
the direct result of chronic alcohol abuse.

•Alcoholic cirrhosis is a debilitating disease that remains among the
top 10 causes of death worldwide.
Alcoholic Liver Disease and
Alcoholic Cirrhosis

•Alcoholic cirrhosis is an irreversible condition that has an estimated
frequency of 10% to 15% among people who consume more than
50 g of alcohol daily over a 10-year period.

•It is characterized by both steatosis and hepatitis, and fibrosis. If left
unchecked and untreated, inflammation of the liver certainly
produces hepatic fibrosis.

•The principal pathogenic process in the development of cirrhosis is
the progressive fibrotic changes that occur within the liver
parenchyma combined with the disruption of the normal hepatic
vasculature.
Alcohol and the Liver
•CIRRHOSIS

–The clinical and laboratory features of alcoholic
cirrhosis are largely similar to those seen in other
causes of cirrhosis

–one exception: affected patients may have
concurrent evidence of alcoholic hepatitis.
• increased ratio of serum AST to ALT,
•jaundice, alkaline phosphatase elevation,
•hematologic abnormalities may coexist with stigmata of
chronic liver disease.

Alcohol and the Liver
• long-term management of alcoholic liver
disease:
– importance of abstinence
– well nourished, and nutritional supplements
–During hospitalizations for decompensation of
alcoholic liver disease, aggressive nutritional
therapy should be instituted
–Complications of cirrhosis that arise in patients
with alcoholic liver disease should be sought and
treated
–end stage alcoholic liver disease should be
considered for liver transplantation


•Young patient admitted to the emergency for
–Jaundice
–confusion

•Labs:
–ALT 2000
–AST 1500
–Total Bilirubin 20
•Direct: 15

•Next step ??

•Abdominal ultra sound

•Other labs test?

•Physical exam

Fulminant hepatic failure

Fulminant hepatic failure
definition

•Rapid development of severe acute liver injury
with impaired function and encephalopathy in
previously normal liver or well compensated
liver disease

–Encephalopathy within 8wks previous healthy
liver

–Encephalopathy within 2 wks of developing
jaundice with previous underlying liver
Subfulminant hepatic failure
definition

•FHF> 8wks – 6 months

•FHF VS sub FHF
–Cerebral edema is common in FHF and rare in sub
FHF
–Renal failure and portal hypertension are more
frequently with sub FHF

Causes of Acute liver failure

Viruses
Hepatitis A, B, C, D, E
Cytomegalovirus
Epstein–Barr virus
Herpes simplex virus 1 and 2
Varicella-zoster virus
Adenovirus
Dengue virus
Medications
Acetaminophen
Anti-tuberculosis (Isoniazid, Rifampin, Pyrazinamide)
Statins
Non-steroidal anti-inflammatory drugs
Sulfa drugs
Phenytoin
Carbamazepine
MDMA (ecstasy)
Flucloxacillin
Ketoconazole
Nitrofurantoin
Immune checkpoint inhibitors
Idiosyncratic drug reactions
Genetic/Autoimmune
Wilson disease
Autoimmune hepatitis
Vascular
Budd–Chiari syndrome
Veno-occlusive disease
Ischemic hepatitis
Herbals/Nutritional Supplements
Multiple agents (Kava Kava, Hydroxycut, Ma Huang, etc.)
Dietary and weight loss supplements
Multivitamins
Toxins
Mushroom (most commonly Amanita phalloides)
Carbon tetrachloride
Yellow phosphorus
Infiltration
Breast cancer
Small-cell lung cancer
Lymphoma
Colon cancer
Melanoma
Multiple myeloma
Pregnancy-related
Acute fatty liver of pregnancy
HELLP syndrome
Pre-eclamptic liver rupture
Other
Sepsis
Partial hepatectomy
Heat stroke
Hemophagocytic lymphohistiocytosis
causes
•Major causes of fulminant hepatic failure
–A- Acetaminophene, hep A, autoimmune hepatitis
–B- Hepatitis B
–C- Hepatitis C, cryptogenic
–D- Hepatitis D, drug
–E- Esoteric causes, Wilson’s disease, Budd-Chiari
–F – Fatty infiltration, acute fatty liver of
pregnancy, Reye’s syndrome

39. –Alcoholic hepatitis is defined by both clinical and
pathologic criteria

•clinically in a patient with a history of heavy alcohol use
and compatible clinical and laboratory findings

•clinical and laboratory features are often adequate for
establishing the diagnosis
Alcohol and the Liver

•ALCOHOLIC HEPATITIS:

–History is essential: information includes:

•amount and duration of alcohol ingestion,

•the possible presence of risk factors for hepatitis B or C

•use of potentially hepatotoxic drugs

•knowledge of prior liver disease.
Loading…
Alcohol and the Liver

•ALCOHOLIC HEPATITIS:

–Presentations
•Asymptomatic (majority of cases)
–Hepatomegaly
–Biochemistry mildly abnormal
–Needs histology for confirmation
•Symptomatic (minority of cases)
–Liver failure

– laboratory features:
Alcohol and the Liver
•ALCOHOLIC HEPATITIS:
–Clinical manifestations
•symptoms at presentation are those with fatty liver but
some patients remain asymptomatic.

•The characteristic signs and symptoms of alcoholic
hepatitis are
–Fever
–Hepatomegaly
–Jaundice
–anorexia
•The presence of stigmata of chronic liver disease (spider
angiomata, palmar erythema, gynecomastia) suggest
advanced disease with underlying cirrhosis.
Alcohol and the Liver
• ALCOHOLIC HEPATITIS: Pathology

–Obligatory features include
•Liver cell necrosis
•Mallory bodies
•Infiltration by neutrophils
•Perivenular distribution of inflammation

–not essential, histologic features include:
•bridging necrosis,
•fatty change,
•bile duct proliferation,
•cholestasis,
•perivenular fibrosis.
Alcoholic Liver Disease and
Alcoholic Cirrhosis

•alcoholic cirrhosis, is defined as a condition in which there is
continuing fibrosis resulting in the subdivision of the liver into
nodules of proliferating hepatocytes surrounded by scar tissue as
the direct result of chronic alcohol abuse.

•Alcoholic cirrhosis is a debilitating disease that remains among the
top 10 causes of death worldwide.
Alcoholic Liver Disease and
Alcoholic Cirrhosis

•Alcoholic cirrhosis is an irreversible condition that has an estimated
frequency of 10% to 15% among people who consume more than
50 g of alcohol daily over a 10-year period.

•It is characterized by both steatosis and hepatitis, and fibrosis. If left
unchecked and untreated, inflammation of the liver certainly
produces hepatic fibrosis.

•The principal pathogenic process in the development of cirrhosis is
the progressive fibrotic changes that occur within the liver
parenchyma combined with the disruption of the normal hepatic
vasculature.
Alcohol and the Liver
•CIRRHOSIS

–The clinical and laboratory features of alcoholic
cirrhosis are largely similar to those seen in other
causes of cirrhosis

–one exception: affected patients may have
concurrent evidence of alcoholic hepatitis.
• increased ratio of serum AST to ALT,
•jaundice, alkaline phosphatase elevation,
•hematologic abnormalities may coexist with stigmata of
chronic liver disease.

Alcohol and the Liver
• long-term management of alcoholic liver
disease:
– importance of abstinence
– well nourished, and nutritional supplements
–During hospitalizations for decompensation of
alcoholic liver disease, aggressive nutritional
therapy should be instituted
–Complications of cirrhosis that arise in patients
with alcoholic liver disease should be sought and
treated
–end stage alcoholic liver disease should be
considered for liver transplantation


•Young patient admitted to the emergency for
–Jaundice
–confusion

•Labs:
–ALT 2000
–AST 1500
–Total Bilirubin 20
•Direct: 15

•Next step ??

•Abdominal ultra sound

•Other labs test?

•Physical exam

Fulminant hepatic failure

Fulminant hepatic failure
definition

•Rapid development of severe acute liver injury
with impaired function and encephalopathy in
previously normal liver or well compensated
liver disease

–Encephalopathy within 8wks previous healthy
liver

–Encephalopathy within 2 wks of developing
jaundice with previous underlying liver
Subfulminant hepatic failure
definition

•FHF> 8wks – 6 months

•FHF VS sub FHF
–Cerebral edema is common in FHF and rare in sub
FHF
–Renal failure and portal hypertension are more
frequently with sub FHF

Causes of Acute liver failure

Viruses
Hepatitis A, B, C, D, E
Cytomegalovirus
Epstein–Barr virus
Herpes simplex virus 1 and 2
Varicella-zoster virus
Adenovirus
Dengue virus
Medications
Acetaminophen
Anti-tuberculosis (Isoniazid, Rifampin, Pyrazinamide)
Statins
Non-steroidal anti-inflammatory drugs
Sulfa drugs
Phenytoin
Carbamazepine
MDMA (ecstasy)
Flucloxacillin
Ketoconazole
Nitrofurantoin
Immune checkpoint inhibitors
Idiosyncratic drug reactions
Genetic/Autoimmune
Wilson disease
Autoimmune hepatitis
Vascular
Budd–Chiari syndrome
Veno-occlusive disease
Ischemic hepatitis
Herbals/Nutritional Supplements
Multiple agents (Kava Kava, Hydroxycut, Ma Huang, etc.)
Dietary and weight loss supplements
Multivitamins
Toxins
Mushroom (most commonly Amanita phalloides)
Carbon tetrachloride
Yellow phosphorus
Infiltration
Breast cancer
Small-cell lung cancer
Lymphoma
Colon cancer
Melanoma
Multiple myeloma
Pregnancy-related
Acute fatty liver of pregnancy
HELLP syndrome
Pre-eclamptic liver rupture
Other
Sepsis
Partial hepatectomy
Heat stroke
Hemophagocytic lymphohistiocytosis
causes
•Major causes of fulminant hepatic failure
–A- Acetaminophene, hep A, autoimmune hepatitis
–B- Hepatitis B
–C- Hepatitis C, cryptogenic
–D- Hepatitis D, drug
–E- Esoteric causes, Wilson’s disease, Budd-Chiari
–F – Fatty infiltration, acute fatty liver of
pregnancy, Reye’s syndrome

40. –Alcoholic hepatitis is defined by both clinical and
pathologic criteria

•clinically in a patient with a history of heavy alcohol use
and compatible clinical and laboratory findings

•clinical and laboratory features are often adequate for
establishing the diagnosis
Alcohol and the Liver

•ALCOHOLIC HEPATITIS:

–History is essential: information includes:

•amount and duration of alcohol ingestion,

•the possible presence of risk factors for hepatitis B or C

•use of potentially hepatotoxic drugs

•knowledge of prior liver disease.
Loading…
Alcohol and the Liver

•ALCOHOLIC HEPATITIS:

–Presentations
•Asymptomatic (majority of cases)
–Hepatomegaly
–Biochemistry mildly abnormal
–Needs histology for confirmation
•Symptomatic (minority of cases)
–Liver failure

– laboratory features:
Alcohol and the Liver
•ALCOHOLIC HEPATITIS:
–Clinical manifestations
•symptoms at presentation are those with fatty liver but
some patients remain asymptomatic.

•The characteristic signs and symptoms of alcoholic
hepatitis are
–Fever
–Hepatomegaly
–Jaundice
–anorexia
•The presence of stigmata of chronic liver disease (spider
angiomata, palmar erythema, gynecomastia) suggest
advanced disease with underlying cirrhosis.
Alcohol and the Liver
• ALCOHOLIC HEPATITIS: Pathology

–Obligatory features include
•Liver cell necrosis
•Mallory bodies
•Infiltration by neutrophils
•Perivenular distribution of inflammation

–not essential, histologic features include:
•bridging necrosis,
•fatty change,
•bile duct proliferation,
•cholestasis,
•perivenular fibrosis.
Alcoholic Liver Disease and
Alcoholic Cirrhosis

•alcoholic cirrhosis, is defined as a condition in which there is
continuing fibrosis resulting in the subdivision of the liver into
nodules of proliferating hepatocytes surrounded by scar tissue as
the direct result of chronic alcohol abuse.

•Alcoholic cirrhosis is a debilitating disease that remains among the
top 10 causes of death worldwide.
Alcoholic Liver Disease and
Alcoholic Cirrhosis

•Alcoholic cirrhosis is an irreversible condition that has an estimated
frequency of 10% to 15% among people who consume more than
50 g of alcohol daily over a 10-year period.

•It is characterized by both steatosis and hepatitis, and fibrosis. If left
unchecked and untreated, inflammation of the liver certainly
produces hepatic fibrosis.

•The principal pathogenic process in the development of cirrhosis is
the progressive fibrotic changes that occur within the liver
parenchyma combined with the disruption of the normal hepatic
vasculature.
Alcohol and the Liver
•CIRRHOSIS

–The clinical and laboratory features of alcoholic
cirrhosis are largely similar to those seen in other
causes of cirrhosis

–one exception: affected patients may have
concurrent evidence of alcoholic hepatitis.
• increased ratio of serum AST to ALT,
•jaundice, alkaline phosphatase elevation,
•hematologic abnormalities may coexist with stigmata of
chronic liver disease.

Alcohol and the Liver
• long-term management of alcoholic liver
disease:
– importance of abstinence
– well nourished, and nutritional supplements
–During hospitalizations for decompensation of
alcoholic liver disease, aggressive nutritional
therapy should be instituted
–Complications of cirrhosis that arise in patients
with alcoholic liver disease should be sought and
treated
–end stage alcoholic liver disease should be
considered for liver transplantation


•Young patient admitted to the emergency for
–Jaundice
–confusion

•Labs:
–ALT 2000
–AST 1500
–Total Bilirubin 20
•Direct: 15

•Next step ??

•Abdominal ultra sound

•Other labs test?

•Physical exam

Fulminant hepatic failure

Fulminant hepatic failure
definition

•Rapid development of severe acute liver injury
with impaired function and encephalopathy in
previously normal liver or well compensated
liver disease

–Encephalopathy within 8wks previous healthy
liver

–Encephalopathy within 2 wks of developing
jaundice with previous underlying liver
Subfulminant hepatic failure
definition

•FHF> 8wks – 6 months

•FHF VS sub FHF
–Cerebral edema is common in FHF and rare in sub
FHF
–Renal failure and portal hypertension are more
frequently with sub FHF

Causes of Acute liver failure

Viruses
Hepatitis A, B, C, D, E
Cytomegalovirus
Epstein–Barr virus
Herpes simplex virus 1 and 2
Varicella-zoster virus
Adenovirus
Dengue virus
Medications
Acetaminophen
Anti-tuberculosis (Isoniazid, Rifampin, Pyrazinamide)
Statins
Non-steroidal anti-inflammatory drugs
Sulfa drugs
Phenytoin
Carbamazepine
MDMA (ecstasy)
Flucloxacillin
Ketoconazole
Nitrofurantoin
Immune checkpoint inhibitors
Idiosyncratic drug reactions
Genetic/Autoimmune
Wilson disease
Autoimmune hepatitis
Vascular
Budd–Chiari syndrome
Veno-occlusive disease
Ischemic hepatitis
Herbals/Nutritional Supplements
Multiple agents (Kava Kava, Hydroxycut, Ma Huang, etc.)
Dietary and weight loss supplements
Multivitamins
Toxins
Mushroom (most commonly Amanita phalloides)
Carbon tetrachloride
Yellow phosphorus
Infiltration
Breast cancer
Small-cell lung cancer
Lymphoma
Colon cancer
Melanoma
Multiple myeloma
Pregnancy-related
Acute fatty liver of pregnancy
HELLP syndrome
Pre-eclamptic liver rupture
Other
Sepsis
Partial hepatectomy
Heat stroke
Hemophagocytic lymphohistiocytosis
causes
•Major causes of fulminant hepatic failure
–A- Acetaminophene, hep A, autoimmune hepatitis
–B- Hepatitis B
–C- Hepatitis C, cryptogenic
–D- Hepatitis D, drug
–E- Esoteric causes, Wilson’s disease, Budd-Chiari
–F – Fatty infiltration, acute fatty liver of
pregnancy, Reye’s syndrome

41. –Alcoholic hepatitis is defined by both clinical and
pathologic criteria

•clinically in a patient with a history of heavy alcohol use
and compatible clinical and laboratory findings

•clinical and laboratory features are often adequate for
establishing the diagnosis
Alcohol and the Liver

•ALCOHOLIC HEPATITIS:

–History is essential: information includes:

•amount and duration of alcohol ingestion,

•the possible presence of risk factors for hepatitis B or C

•use of potentially hepatotoxic drugs

•knowledge of prior liver disease.
Loading…
Alcohol and the Liver

•ALCOHOLIC HEPATITIS:

–Presentations
•Asymptomatic (majority of cases)
–Hepatomegaly
–Biochemistry mildly abnormal
–Needs histology for confirmation
•Symptomatic (minority of cases)
–Liver failure

– laboratory features:
Alcohol and the Liver
•ALCOHOLIC HEPATITIS:
–Clinical manifestations
•symptoms at presentation are those with fatty liver but
some patients remain asymptomatic.

•The characteristic signs and symptoms of alcoholic
hepatitis are
–Fever
–Hepatomegaly
–Jaundice
–anorexia
•The presence of stigmata of chronic liver disease (spider
angiomata, palmar erythema, gynecomastia) suggest
advanced disease with underlying cirrhosis.
Alcohol and the Liver
• ALCOHOLIC HEPATITIS: Pathology

–Obligatory features include
•Liver cell necrosis
•Mallory bodies
•Infiltration by neutrophils
•Perivenular distribution of inflammation

–not essential, histologic features include:
•bridging necrosis,
•fatty change,
•bile duct proliferation,
•cholestasis,
•perivenular fibrosis.
Alcoholic Liver Disease and
Alcoholic Cirrhosis

•alcoholic cirrhosis, is defined as a condition in which there is
continuing fibrosis resulting in the subdivision of the liver into
nodules of proliferating hepatocytes surrounded by scar tissue as
the direct result of chronic alcohol abuse.

•Alcoholic cirrhosis is a debilitating disease that remains among the
top 10 causes of death worldwide.
Alcoholic Liver Disease and
Alcoholic Cirrhosis

•Alcoholic cirrhosis is an irreversible condition that has an estimated
frequency of 10% to 15% among people who consume more than
50 g of alcohol daily over a 10-year period.

•It is characterized by both steatosis and hepatitis, and fibrosis. If left
unchecked and untreated, inflammation of the liver certainly
produces hepatic fibrosis.

•The principal pathogenic process in the development of cirrhosis is
the progressive fibrotic changes that occur within the liver
parenchyma combined with the disruption of the normal hepatic
vasculature.
Alcohol and the Liver
•CIRRHOSIS

–The clinical and laboratory features of alcoholic
cirrhosis are largely similar to those seen in other
causes of cirrhosis

–one exception: affected patients may have
concurrent evidence of alcoholic hepatitis.
• increased ratio of serum AST to ALT,
•jaundice, alkaline phosphatase elevation,
•hematologic abnormalities may coexist with stigmata of
chronic liver disease.

Alcohol and the Liver
• long-term management of alcoholic liver
disease:
– importance of abstinence
– well nourished, and nutritional supplements
–During hospitalizations for decompensation of
alcoholic liver disease, aggressive nutritional
therapy should be instituted
–Complications of cirrhosis that arise in patients
with alcoholic liver disease should be sought and
treated
–end stage alcoholic liver disease should be
considered for liver transplantation


•Young patient admitted to the emergency for
–Jaundice
–confusion

•Labs:
–ALT 2000
–AST 1500
–Total Bilirubin 20
•Direct: 15

•Next step ??

•Abdominal ultra sound

•Other labs test?

•Physical exam

Fulminant hepatic failure

Fulminant hepatic failure
definition

•Rapid development of severe acute liver injury
with impaired function and encephalopathy in
previously normal liver or well compensated
liver disease

–Encephalopathy within 8wks previous healthy
liver

–Encephalopathy within 2 wks of developing
jaundice with previous underlying liver
Subfulminant hepatic failure
definition

•FHF> 8wks – 6 months

•FHF VS sub FHF
–Cerebral edema is common in FHF and rare in sub
FHF
–Renal failure and portal hypertension are more
frequently with sub FHF

Causes of Acute liver failure

Viruses
Hepatitis A, B, C, D, E
Cytomegalovirus
Epstein–Barr virus
Herpes simplex virus 1 and 2
Varicella-zoster virus
Adenovirus
Dengue virus
Medications
Acetaminophen
Anti-tuberculosis (Isoniazid, Rifampin, Pyrazinamide)
Statins
Non-steroidal anti-inflammatory drugs
Sulfa drugs
Phenytoin
Carbamazepine
MDMA (ecstasy)
Flucloxacillin
Ketoconazole
Nitrofurantoin
Immune checkpoint inhibitors
Idiosyncratic drug reactions
Genetic/Autoimmune
Wilson disease
Autoimmune hepatitis
Vascular
Budd–Chiari syndrome
Veno-occlusive disease
Ischemic hepatitis
Herbals/Nutritional Supplements
Multiple agents (Kava Kava, Hydroxycut, Ma Huang, etc.)
Dietary and weight loss supplements
Multivitamins
Toxins
Mushroom (most commonly Amanita phalloides)
Carbon tetrachloride
Yellow phosphorus
Infiltration
Breast cancer
Small-cell lung cancer
Lymphoma
Colon cancer
Melanoma
Multiple myeloma
Pregnancy-related
Acute fatty liver of pregnancy
HELLP syndrome
Pre-eclamptic liver rupture
Other
Sepsis
Partial hepatectomy
Heat stroke
Hemophagocytic lymphohistiocytosis
causes
•Major causes of fulminant hepatic failure
–A- Acetaminophene, hep A, autoimmune hepatitis
–B- Hepatitis B
–C- Hepatitis C, cryptogenic
–D- Hepatitis D, drug
–E- Esoteric causes, Wilson’s disease, Budd-Chiari
–F – Fatty infiltration, acute fatty liver of
pregnancy, Reye’s syndrome

42. –Alcoholic hepatitis is defined by both clinical and
pathologic criteria

•clinically in a patient with a history of heavy alcohol use
and compatible clinical and laboratory findings

•clinical and laboratory features are often adequate for
establishing the diagnosis
Alcohol and the Liver

•ALCOHOLIC HEPATITIS:

–History is essential: information includes:

•amount and duration of alcohol ingestion,

•the possible presence of risk factors for hepatitis B or C

•use of potentially hepatotoxic drugs

•knowledge of prior liver disease.
Loading…
Alcohol and the Liver

•ALCOHOLIC HEPATITIS:

–Presentations
•Asymptomatic (majority of cases)
–Hepatomegaly
–Biochemistry mildly abnormal
–Needs histology for confirmation
•Symptomatic (minority of cases)
–Liver failure

– laboratory features:
Alcohol and the Liver
•ALCOHOLIC HEPATITIS:
–Clinical manifestations
•symptoms at presentation are those with fatty liver but
some patients remain asymptomatic.

•The characteristic signs and symptoms of alcoholic
hepatitis are
–Fever
–Hepatomegaly
–Jaundice
–anorexia
•The presence of stigmata of chronic liver disease (spider
angiomata, palmar erythema, gynecomastia) suggest
advanced disease with underlying cirrhosis.
Alcohol and the Liver
• ALCOHOLIC HEPATITIS: Pathology

–Obligatory features include
•Liver cell necrosis
•Mallory bodies
•Infiltration by neutrophils
•Perivenular distribution of inflammation

–not essential, histologic features include:
•bridging necrosis,
•fatty change,
•bile duct proliferation,
•cholestasis,
•perivenular fibrosis.
Alcoholic Liver Disease and
Alcoholic Cirrhosis

•alcoholic cirrhosis, is defined as a condition in which there is
continuing fibrosis resulting in the subdivision of the liver into
nodules of proliferating hepatocytes surrounded by scar tissue as
the direct result of chronic alcohol abuse.

•Alcoholic cirrhosis is a debilitating disease that remains among the
top 10 causes of death worldwide.
Alcoholic Liver Disease and
Alcoholic Cirrhosis

•Alcoholic cirrhosis is an irreversible condition that has an estimated
frequency of 10% to 15% among people who consume more than
50 g of alcohol daily over a 10-year period.

•It is characterized by both steatosis and hepatitis, and fibrosis. If left
unchecked and untreated, inflammation of the liver certainly
produces hepatic fibrosis.

•The principal pathogenic process in the development of cirrhosis is
the progressive fibrotic changes that occur within the liver
parenchyma combined with the disruption of the normal hepatic
vasculature.
Alcohol and the Liver
•CIRRHOSIS

–The clinical and laboratory features of alcoholic
cirrhosis are largely similar to those seen in other
causes of cirrhosis

–one exception: affected patients may have
concurrent evidence of alcoholic hepatitis.
• increased ratio of serum AST to ALT,
•jaundice, alkaline phosphatase elevation,
•hematologic abnormalities may coexist with stigmata of
chronic liver disease.

Alcohol and the Liver
• long-term management of alcoholic liver
disease:
– importance of abstinence
– well nourished, and nutritional supplements
–During hospitalizations for decompensation of
alcoholic liver disease, aggressive nutritional
therapy should be instituted
–Complications of cirrhosis that arise in patients
with alcoholic liver disease should be sought and
treated
–end stage alcoholic liver disease should be
considered for liver transplantation


•Young patient admitted to the emergency for
–Jaundice
–confusion

•Labs:
–ALT 2000
–AST 1500
–Total Bilirubin 20
•Direct: 15

•Next step ??

•Abdominal ultra sound

•Other labs test?

•Physical exam

Fulminant hepatic failure

Fulminant hepatic failure
definition

•Rapid development of severe acute liver injury
with impaired function and encephalopathy in
previously normal liver or well compensated
liver disease

–Encephalopathy within 8wks previous healthy
liver

–Encephalopathy within 2 wks of developing
jaundice with previous underlying liver
Subfulminant hepatic failure
definition

•FHF> 8wks – 6 months

•FHF VS sub FHF
–Cerebral edema is common in FHF and rare in sub
FHF
–Renal failure and portal hypertension are more
frequently with sub FHF

Causes of Acute liver failure

Viruses
Hepatitis A, B, C, D, E
Cytomegalovirus
Epstein–Barr virus
Herpes simplex virus 1 and 2
Varicella-zoster virus
Adenovirus
Dengue virus
Medications
Acetaminophen
Anti-tuberculosis (Isoniazid, Rifampin, Pyrazinamide)
Statins
Non-steroidal anti-inflammatory drugs
Sulfa drugs
Phenytoin
Carbamazepine
MDMA (ecstasy)
Flucloxacillin
Ketoconazole
Nitrofurantoin
Immune checkpoint inhibitors
Idiosyncratic drug reactions
Genetic/Autoimmune
Wilson disease
Autoimmune hepatitis
Vascular
Budd–Chiari syndrome
Veno-occlusive disease
Ischemic hepatitis
Herbals/Nutritional Supplements
Multiple agents (Kava Kava, Hydroxycut, Ma Huang, etc.)
Dietary and weight loss supplements
Multivitamins
Toxins
Mushroom (most commonly Amanita phalloides)
Carbon tetrachloride
Yellow phosphorus
Infiltration
Breast cancer
Small-cell lung cancer
Lymphoma
Colon cancer
Melanoma
Multiple myeloma
Pregnancy-related
Acute fatty liver of pregnancy
HELLP syndrome
Pre-eclamptic liver rupture
Other
Sepsis
Partial hepatectomy
Heat stroke
Hemophagocytic lymphohistiocytosis
causes
•Major causes of fulminant hepatic failure
–A- Acetaminophene, hep A, autoimmune hepatitis
–B- Hepatitis B
–C- Hepatitis C, cryptogenic
–D- Hepatitis D, drug
–E- Esoteric causes, Wilson’s disease, Budd-Chiari
–F – Fatty infiltration, acute fatty liver of
pregnancy, Reye’s syndrome

43. –Alcoholic hepatitis is defined by both clinical and
pathologic criteria

•clinically in a patient with a history of heavy alcohol use
and compatible clinical and laboratory findings

•clinical and laboratory features are often adequate for
establishing the diagnosis
Alcohol and the Liver

•ALCOHOLIC HEPATITIS:

–History is essential: information includes:

•amount and duration of alcohol ingestion,

•the possible presence of risk factors for hepatitis B or C

•use of potentially hepatotoxic drugs

•knowledge of prior liver disease.
Loading…
Alcohol and the Liver

•ALCOHOLIC HEPATITIS:

–Presentations
•Asymptomatic (majority of cases)
–Hepatomegaly
–Biochemistry mildly abnormal
–Needs histology for confirmation
•Symptomatic (minority of cases)
–Liver failure

– laboratory features:
Alcohol and the Liver
•ALCOHOLIC HEPATITIS:
–Clinical manifestations
•symptoms at presentation are those with fatty liver but
some patients remain asymptomatic.

•The characteristic signs and symptoms of alcoholic
hepatitis are
–Fever
–Hepatomegaly
–Jaundice
–anorexia
•The presence of stigmata of chronic liver disease (spider
angiomata, palmar erythema, gynecomastia) suggest
advanced disease with underlying cirrhosis.
Alcohol and the Liver
• ALCOHOLIC HEPATITIS: Pathology

–Obligatory features include
•Liver cell necrosis
•Mallory bodies
•Infiltration by neutrophils
•Perivenular distribution of inflammation

–not essential, histologic features include:
•bridging necrosis,
•fatty change,
•bile duct proliferation,
•cholestasis,
•perivenular fibrosis.
Alcoholic Liver Disease and
Alcoholic Cirrhosis

•alcoholic cirrhosis, is defined as a condition in which there is
continuing fibrosis resulting in the subdivision of the liver into
nodules of proliferating hepatocytes surrounded by scar tissue as
the direct result of chronic alcohol abuse.

•Alcoholic cirrhosis is a debilitating disease that remains among the
top 10 causes of death worldwide.
Alcoholic Liver Disease and
Alcoholic Cirrhosis

•Alcoholic cirrhosis is an irreversible condition that has an estimated
frequency of 10% to 15% among people who consume more than
50 g of alcohol daily over a 10-year period.

•It is characterized by both steatosis and hepatitis, and fibrosis. If left
unchecked and untreated, inflammation of the liver certainly
produces hepatic fibrosis.

•The principal pathogenic process in the development of cirrhosis is
the progressive fibrotic changes that occur within the liver
parenchyma combined with the disruption of the normal hepatic
vasculature.
Alcohol and the Liver
•CIRRHOSIS

–The clinical and laboratory features of alcoholic
cirrhosis are largely similar to those seen in other
causes of cirrhosis

–one exception: affected patients may have
concurrent evidence of alcoholic hepatitis.
• increased ratio of serum AST to ALT,
•jaundice, alkaline phosphatase elevation,
•hematologic abnormalities may coexist with stigmata of
chronic liver disease.

Alcohol and the Liver
• long-term management of alcoholic liver
disease:
– importance of abstinence
– well nourished, and nutritional supplements
–During hospitalizations for decompensation of
alcoholic liver disease, aggressive nutritional
therapy should be instituted
–Complications of cirrhosis that arise in patients
with alcoholic liver disease should be sought and
treated
–end stage alcoholic liver disease should be
considered for liver transplantation


•Young patient admitted to the emergency for
–Jaundice
–confusion

•Labs:
–ALT 2000
–AST 1500
–Total Bilirubin 20
•Direct: 15

•Next step ??

•Abdominal ultra sound

•Other labs test?

•Physical exam

Fulminant hepatic failure

Fulminant hepatic failure
definition

•Rapid development of severe acute liver injury
with impaired function and encephalopathy in
previously normal liver or well compensated
liver disease

–Encephalopathy within 8wks previous healthy
liver

–Encephalopathy within 2 wks of developing
jaundice with previous underlying liver
Subfulminant hepatic failure
definition

•FHF> 8wks – 6 months

•FHF VS sub FHF
–Cerebral edema is common in FHF and rare in sub
FHF
–Renal failure and portal hypertension are more
frequently with sub FHF

Causes of Acute liver failure

Viruses
Hepatitis A, B, C, D, E
Cytomegalovirus
Epstein–Barr virus
Herpes simplex virus 1 and 2
Varicella-zoster virus
Adenovirus
Dengue virus
Medications
Acetaminophen
Anti-tuberculosis (Isoniazid, Rifampin, Pyrazinamide)
Statins
Non-steroidal anti-inflammatory drugs
Sulfa drugs
Phenytoin
Carbamazepine
MDMA (ecstasy)
Flucloxacillin
Ketoconazole
Nitrofurantoin
Immune checkpoint inhibitors
Idiosyncratic drug reactions
Genetic/Autoimmune
Wilson disease
Autoimmune hepatitis
Vascular
Budd–Chiari syndrome
Veno-occlusive disease
Ischemic hepatitis
Herbals/Nutritional Supplements
Multiple agents (Kava Kava, Hydroxycut, Ma Huang, etc.)
Dietary and weight loss supplements
Multivitamins
Toxins
Mushroom (most commonly Amanita phalloides)
Carbon tetrachloride
Yellow phosphorus
Infiltration
Breast cancer
Small-cell lung cancer
Lymphoma
Colon cancer
Melanoma
Multiple myeloma
Pregnancy-related
Acute fatty liver of pregnancy
HELLP syndrome
Pre-eclamptic liver rupture
Other
Sepsis
Partial hepatectomy
Heat stroke
Hemophagocytic lymphohistiocytosis
causes
•Major causes of fulminant hepatic failure
–A- Acetaminophene, hep A, autoimmune hepatitis
–B- Hepatitis B
–C- Hepatitis C, cryptogenic
–D- Hepatitis D, drug
–E- Esoteric causes, Wilson’s disease, Budd-Chiari
–F – Fatty infiltration, acute fatty liver of
pregnancy, Reye’s syndrome

44. –Alcoholic hepatitis is defined by both clinical and
pathologic criteria

•clinically in a patient with a history of heavy alcohol use
and compatible clinical and laboratory findings

•clinical and laboratory features are often adequate for
establishing the diagnosis
Alcohol and the Liver

•ALCOHOLIC HEPATITIS:

–History is essential: information includes:

•amount and duration of alcohol ingestion,

•the possible presence of risk factors for hepatitis B or C

•use of potentially hepatotoxic drugs

•knowledge of prior liver disease.
Loading…
Alcohol and the Liver

•ALCOHOLIC HEPATITIS:

–Presentations
•Asymptomatic (majority of cases)
–Hepatomegaly
–Biochemistry mildly abnormal
–Needs histology for confirmation
•Symptomatic (minority of cases)
–Liver failure

– laboratory features:
Alcohol and the Liver
•ALCOHOLIC HEPATITIS:
–Clinical manifestations
•symptoms at presentation are those with fatty liver but
some patients remain asymptomatic.

•The characteristic signs and symptoms of alcoholic
hepatitis are
–Fever
–Hepatomegaly
–Jaundice
–anorexia
•The presence of stigmata of chronic liver disease (spider
angiomata, palmar erythema, gynecomastia) suggest
advanced disease with underlying cirrhosis.
Alcohol and the Liver
• ALCOHOLIC HEPATITIS: Pathology

–Obligatory features include
•Liver cell necrosis
•Mallory bodies
•Infiltration by neutrophils
•Perivenular distribution of inflammation

–not essential, histologic features include:
•bridging necrosis,
•fatty change,
•bile duct proliferation,
•cholestasis,
•perivenular fibrosis.
Alcoholic Liver Disease and
Alcoholic Cirrhosis

•alcoholic cirrhosis, is defined as a condition in which there is
continuing fibrosis resulting in the subdivision of the liver into
nodules of proliferating hepatocytes surrounded by scar tissue as
the direct result of chronic alcohol abuse.

•Alcoholic cirrhosis is a debilitating disease that remains among the
top 10 causes of death worldwide.
Alcoholic Liver Disease and
Alcoholic Cirrhosis

•Alcoholic cirrhosis is an irreversible condition that has an estimated
frequency of 10% to 15% among people who consume more than
50 g of alcohol daily over a 10-year period.

•It is characterized by both steatosis and hepatitis, and fibrosis. If left
unchecked and untreated, inflammation of the liver certainly
produces hepatic fibrosis.

•The principal pathogenic process in the development of cirrhosis is
the progressive fibrotic changes that occur within the liver
parenchyma combined with the disruption of the normal hepatic
vasculature.
Alcohol and the Liver
•CIRRHOSIS

–The clinical and laboratory features of alcoholic
cirrhosis are largely similar to those seen in other
causes of cirrhosis

–one exception: affected patients may have
concurrent evidence of alcoholic hepatitis.
• increased ratio of serum AST to ALT,
•jaundice, alkaline phosphatase elevation,
•hematologic abnormalities may coexist with stigmata of
chronic liver disease.

Alcohol and the Liver
• long-term management of alcoholic liver
disease:
– importance of abstinence
– well nourished, and nutritional supplements
–During hospitalizations for decompensation of
alcoholic liver disease, aggressive nutritional
therapy should be instituted
–Complications of cirrhosis that arise in patients
with alcoholic liver disease should be sought and
treated
–end stage alcoholic liver disease should be
considered for liver transplantation


•Young patient admitted to the emergency for
–Jaundice
–confusion

•Labs:
–ALT 2000
–AST 1500
–Total Bilirubin 20
•Direct: 15

•Next step ??

•Abdominal ultra sound

•Other labs test?

•Physical exam

Fulminant hepatic failure

Fulminant hepatic failure
definition

•Rapid development of severe acute liver injury
with impaired function and encephalopathy in
previously normal liver or well compensated
liver disease

–Encephalopathy within 8wks previous healthy
liver

–Encephalopathy within 2 wks of developing
jaundice with previous underlying liver
Subfulminant hepatic failure
definition

•FHF> 8wks – 6 months

•FHF VS sub FHF
–Cerebral edema is common in FHF and rare in sub
FHF
–Renal failure and portal hypertension are more
frequently with sub FHF

Causes of Acute liver failure

Viruses
Hepatitis A, B, C, D, E
Cytomegalovirus
Epstein–Barr virus
Herpes simplex virus 1 and 2
Varicella-zoster virus
Adenovirus
Dengue virus
Medications
Acetaminophen
Anti-tuberculosis (Isoniazid, Rifampin, Pyrazinamide)
Statins
Non-steroidal anti-inflammatory drugs
Sulfa drugs
Phenytoin
Carbamazepine
MDMA (ecstasy)
Flucloxacillin
Ketoconazole
Nitrofurantoin
Immune checkpoint inhibitors
Idiosyncratic drug reactions
Genetic/Autoimmune
Wilson disease
Autoimmune hepatitis
Vascular
Budd–Chiari syndrome
Veno-occlusive disease
Ischemic hepatitis
Herbals/Nutritional Supplements
Multiple agents (Kava Kava, Hydroxycut, Ma Huang, etc.)
Dietary and weight loss supplements
Multivitamins
Toxins
Mushroom (most commonly Amanita phalloides)
Carbon tetrachloride
Yellow phosphorus
Infiltration
Breast cancer
Small-cell lung cancer
Lymphoma
Colon cancer
Melanoma
Multiple myeloma
Pregnancy-related
Acute fatty liver of pregnancy
HELLP syndrome
Pre-eclamptic liver rupture
Other
Sepsis
Partial hepatectomy
Heat stroke
Hemophagocytic lymphohistiocytosis
causes
•Major causes of fulminant hepatic failure
–A- Acetaminophene, hep A, autoimmune hepatitis
–B- Hepatitis B
–C- Hepatitis C, cryptogenic
–D- Hepatitis D, drug
–E- Esoteric causes, Wilson’s disease, Budd-Chiari
–F – Fatty infiltration, acute fatty liver of
pregnancy, Reye’s syndrome

45. –Alcoholic hepatitis is defined by both clinical and
pathologic criteria

•clinically in a patient with a history of heavy alcohol use
and compatible clinical and laboratory findings

•clinical and laboratory features are often adequate for
establishing the diagnosis
Alcohol and the Liver

•ALCOHOLIC HEPATITIS:

–History is essential: information includes:

•amount and duration of alcohol ingestion,

•the possible presence of risk factors for hepatitis B or C

•use of potentially hepatotoxic drugs

•knowledge of prior liver disease.
Loading…
Alcohol and the Liver

•ALCOHOLIC HEPATITIS:

–Presentations
•Asymptomatic (majority of cases)
–Hepatomegaly
–Biochemistry mildly abnormal
–Needs histology for confirmation
•Symptomatic (minority of cases)
–Liver failure

– laboratory features:
Alcohol and the Liver
•ALCOHOLIC HEPATITIS:
–Clinical manifestations
•symptoms at presentation are those with fatty liver but
some patients remain asymptomatic.

•The characteristic signs and symptoms of alcoholic
hepatitis are
–Fever
–Hepatomegaly
–Jaundice
–anorexia
•The presence of stigmata of chronic liver disease (spider
angiomata, palmar erythema, gynecomastia) suggest
advanced disease with underlying cirrhosis.
Alcohol and the Liver
• ALCOHOLIC HEPATITIS: Pathology

–Obligatory features include
•Liver cell necrosis
•Mallory bodies
•Infiltration by neutrophils
•Perivenular distribution of inflammation

–not essential, histologic features include:
•bridging necrosis,
•fatty change,
•bile duct proliferation,
•cholestasis,
•perivenular fibrosis.
Alcoholic Liver Disease and
Alcoholic Cirrhosis

•alcoholic cirrhosis, is defined as a condition in which there is
continuing fibrosis resulting in the subdivision of the liver into
nodules of proliferating hepatocytes surrounded by scar tissue as
the direct result of chronic alcohol abuse.

•Alcoholic cirrhosis is a debilitating disease that remains among the
top 10 causes of death worldwide.
Alcoholic Liver Disease and
Alcoholic Cirrhosis

•Alcoholic cirrhosis is an irreversible condition that has an estimated
frequency of 10% to 15% among people who consume more than
50 g of alcohol daily over a 10-year period.

•It is characterized by both steatosis and hepatitis, and fibrosis. If left
unchecked and untreated, inflammation of the liver certainly
produces hepatic fibrosis.

•The principal pathogenic process in the development of cirrhosis is
the progressive fibrotic changes that occur within the liver
parenchyma combined with the disruption of the normal hepatic
vasculature.
Alcohol and the Liver
•CIRRHOSIS

–The clinical and laboratory features of alcoholic
cirrhosis are largely similar to those seen in other
causes of cirrhosis

–one exception: affected patients may have
concurrent evidence of alcoholic hepatitis.
• increased ratio of serum AST to ALT,
•jaundice, alkaline phosphatase elevation,
•hematologic abnormalities may coexist with stigmata of
chronic liver disease.

Alcohol and the Liver
• long-term management of alcoholic liver
disease:
– importance of abstinence
– well nourished, and nutritional supplements
–During hospitalizations for decompensation of
alcoholic liver disease, aggressive nutritional
therapy should be instituted
–Complications of cirrhosis that arise in patients
with alcoholic liver disease should be sought and
treated
–end stage alcoholic liver disease should be
considered for liver transplantation


•Young patient admitted to the emergency for
–Jaundice
–confusion

•Labs:
–ALT 2000
–AST 1500
–Total Bilirubin 20
•Direct: 15

•Next step ??

•Abdominal ultra sound

•Other labs test?

•Physical exam

Fulminant hepatic failure

Fulminant hepatic failure
definition

•Rapid development of severe acute liver injury
with impaired function and encephalopathy in
previously normal liver or well compensated
liver disease

–Encephalopathy within 8wks previous healthy
liver

–Encephalopathy within 2 wks of developing
jaundice with previous underlying liver
Subfulminant hepatic failure
definition

•FHF> 8wks – 6 months

•FHF VS sub FHF
–Cerebral edema is common in FHF and rare in sub
FHF
–Renal failure and portal hypertension are more
frequently with sub FHF

Causes of Acute liver failure

Viruses
Hepatitis A, B, C, D, E
Cytomegalovirus
Epstein–Barr virus
Herpes simplex virus 1 and 2
Varicella-zoster virus
Adenovirus
Dengue virus
Medications
Acetaminophen
Anti-tuberculosis (Isoniazid, Rifampin, Pyrazinamide)
Statins
Non-steroidal anti-inflammatory drugs
Sulfa drugs
Phenytoin
Carbamazepine
MDMA (ecstasy)
Flucloxacillin
Ketoconazole
Nitrofurantoin
Immune checkpoint inhibitors
Idiosyncratic drug reactions
Genetic/Autoimmune
Wilson disease
Autoimmune hepatitis
Vascular
Budd–Chiari syndrome
Veno-occlusive disease
Ischemic hepatitis
Herbals/Nutritional Supplements
Multiple agents (Kava Kava, Hydroxycut, Ma Huang, etc.)
Dietary and weight loss supplements
Multivitamins
Toxins
Mushroom (most commonly Amanita phalloides)
Carbon tetrachloride
Yellow phosphorus
Infiltration
Breast cancer
Small-cell lung cancer
Lymphoma
Colon cancer
Melanoma
Multiple myeloma
Pregnancy-related
Acute fatty liver of pregnancy
HELLP syndrome
Pre-eclamptic liver rupture
Other
Sepsis
Partial hepatectomy
Heat stroke
Hemophagocytic lymphohistiocytosis
causes
•Major causes of fulminant hepatic failure
–A- Acetaminophene, hep A, autoimmune hepatitis
–B- Hepatitis B
–C- Hepatitis C, cryptogenic
–D- Hepatitis D, drug
–E- Esoteric causes, Wilson’s disease, Budd-Chiari
–F – Fatty infiltration, acute fatty liver of
pregnancy, Reye’s syndrome

46. –Alcoholic hepatitis is defined by both clinical and
pathologic criteria

•clinically in a patient with a history of heavy alcohol use
and compatible clinical and laboratory findings

•clinical and laboratory features are often adequate for
establishing the diagnosis
Alcohol and the Liver

•ALCOHOLIC HEPATITIS:

–History is essential: information includes:

•amount and duration of alcohol ingestion,

•the possible presence of risk factors for hepatitis B or C

•use of potentially hepatotoxic drugs

•knowledge of prior liver disease.
Loading…
Alcohol and the Liver

•ALCOHOLIC HEPATITIS:

–Presentations
•Asymptomatic (majority of cases)
–Hepatomegaly
–Biochemistry mildly abnormal
–Needs histology for confirmation
•Symptomatic (minority of cases)
–Liver failure

– laboratory features:
Alcohol and the Liver
•ALCOHOLIC HEPATITIS:
–Clinical manifestations
•symptoms at presentation are those with fatty liver but
some patients remain asymptomatic.

•The characteristic signs and symptoms of alcoholic
hepatitis are
–Fever
–Hepatomegaly
–Jaundice
–anorexia
•The presence of stigmata of chronic liver disease (spider
angiomata, palmar erythema, gynecomastia) suggest
advanced disease with underlying cirrhosis.
Alcohol and the Liver
• ALCOHOLIC HEPATITIS: Pathology

–Obligatory features include
•Liver cell necrosis
•Mallory bodies
•Infiltration by neutrophils
•Perivenular distribution of inflammation

–not essential, histologic features include:
•bridging necrosis,
•fatty change,
•bile duct proliferation,
•cholestasis,
•perivenular fibrosis.
Alcoholic Liver Disease and
Alcoholic Cirrhosis

•alcoholic cirrhosis, is defined as a condition in which there is
continuing fibrosis resulting in the subdivision of the liver into
nodules of proliferating hepatocytes surrounded by scar tissue as
the direct result of chronic alcohol abuse.

•Alcoholic cirrhosis is a debilitating disease that remains among the
top 10 causes of death worldwide.
Alcoholic Liver Disease and
Alcoholic Cirrhosis

•Alcoholic cirrhosis is an irreversible condition that has an estimated
frequency of 10% to 15% among people who consume more than
50 g of alcohol daily over a 10-year period.

•It is characterized by both steatosis and hepatitis, and fibrosis. If left
unchecked and untreated, inflammation of the liver certainly
produces hepatic fibrosis.

•The principal pathogenic process in the development of cirrhosis is
the progressive fibrotic changes that occur within the liver
parenchyma combined with the disruption of the normal hepatic
vasculature.
Alcohol and the Liver
•CIRRHOSIS

–The clinical and laboratory features of alcoholic
cirrhosis are largely similar to those seen in other
causes of cirrhosis

–one exception: affected patients may have
concurrent evidence of alcoholic hepatitis.
• increased ratio of serum AST to ALT,
•jaundice, alkaline phosphatase elevation,
•hematologic abnormalities may coexist with stigmata of
chronic liver disease.

Alcohol and the Liver
• long-term management of alcoholic liver
disease:
– importance of abstinence
– well nourished, and nutritional supplements
–During hospitalizations for decompensation of
alcoholic liver disease, aggressive nutritional
therapy should be instituted
–Complications of cirrhosis that arise in patients
with alcoholic liver disease should be sought and
treated
–end stage alcoholic liver disease should be
considered for liver transplantation


•Young patient admitted to the emergency for
–Jaundice
–confusion

•Labs:
–ALT 2000
–AST 1500
–Total Bilirubin 20
•Direct: 15

•Next step ??

•Abdominal ultra sound

•Other labs test?

•Physical exam

Fulminant hepatic failure

Fulminant hepatic failure
definition

•Rapid development of severe acute liver injury
with impaired function and encephalopathy in
previously normal liver or well compensated
liver disease

–Encephalopathy within 8wks previous healthy
liver

–Encephalopathy within 2 wks of developing
jaundice with previous underlying liver
Subfulminant hepatic failure
definition

•FHF> 8wks – 6 months

•FHF VS sub FHF
–Cerebral edema is common in FHF and rare in sub
FHF
–Renal failure and portal hypertension are more
frequently with sub FHF

Causes of Acute liver failure

Viruses
Hepatitis A, B, C, D, E
Cytomegalovirus
Epstein–Barr virus
Herpes simplex virus 1 and 2
Varicella-zoster virus
Adenovirus
Dengue virus
Medications
Acetaminophen
Anti-tuberculosis (Isoniazid, Rifampin, Pyrazinamide)
Statins
Non-steroidal anti-inflammatory drugs
Sulfa drugs
Phenytoin
Carbamazepine
MDMA (ecstasy)
Flucloxacillin
Ketoconazole
Nitrofurantoin
Immune checkpoint inhibitors
Idiosyncratic drug reactions
Genetic/Autoimmune
Wilson disease
Autoimmune hepatitis
Vascular
Budd–Chiari syndrome
Veno-occlusive disease
Ischemic hepatitis
Herbals/Nutritional Supplements
Multiple agents (Kava Kava, Hydroxycut, Ma Huang, etc.)
Dietary and weight loss supplements
Multivitamins
Toxins
Mushroom (most commonly Amanita phalloides)
Carbon tetrachloride
Yellow phosphorus
Infiltration
Breast cancer
Small-cell lung cancer
Lymphoma
Colon cancer
Melanoma
Multiple myeloma
Pregnancy-related
Acute fatty liver of pregnancy
HELLP syndrome
Pre-eclamptic liver rupture
Other
Sepsis
Partial hepatectomy
Heat stroke
Hemophagocytic lymphohistiocytosis
causes
•Major causes of fulminant hepatic failure
–A- Acetaminophene, hep A, autoimmune hepatitis
–B- Hepatitis B
–C- Hepatitis C, cryptogenic
–D- Hepatitis D, drug
–E- Esoteric causes, Wilson’s disease, Budd-Chiari
–F – Fatty infiltration, acute fatty liver of
pregnancy, Reye’s syndrome

47. –Alcoholic hepatitis is defined by both clinical and
pathologic criteria

•clinically in a patient with a history of heavy alcohol use
and compatible clinical and laboratory findings

•clinical and laboratory features are often adequate for
establishing the diagnosis
Alcohol and the Liver

•ALCOHOLIC HEPATITIS:

–History is essential: information includes:

•amount and duration of alcohol ingestion,

•the possible presence of risk factors for hepatitis B or C

•use of potentially hepatotoxic drugs

•knowledge of prior liver disease.
Loading…
Alcohol and the Liver

•ALCOHOLIC HEPATITIS:

–Presentations
•Asymptomatic (majority of cases)
–Hepatomegaly
–Biochemistry mildly abnormal
–Needs histology for confirmation
•Symptomatic (minority of cases)
–Liver failure

– laboratory features:
Alcohol and the Liver
•ALCOHOLIC HEPATITIS:
–Clinical manifestations
•symptoms at presentation are those with fatty liver but
some patients remain asymptomatic.

•The characteristic signs and symptoms of alcoholic
hepatitis are
–Fever
–Hepatomegaly
–Jaundice
–anorexia
•The presence of stigmata of chronic liver disease (spider
angiomata, palmar erythema, gynecomastia) suggest
advanced disease with underlying cirrhosis.
Alcohol and the Liver
• ALCOHOLIC HEPATITIS: Pathology

–Obligatory features include
•Liver cell necrosis
•Mallory bodies
•Infiltration by neutrophils
•Perivenular distribution of inflammation

–not essential, histologic features include:
•bridging necrosis,
•fatty change,
•bile duct proliferation,
•cholestasis,
•perivenular fibrosis.
Alcoholic Liver Disease and
Alcoholic Cirrhosis

•alcoholic cirrhosis, is defined as a condition in which there is
continuing fibrosis resulting in the subdivision of the liver into
nodules of proliferating hepatocytes surrounded by scar tissue as
the direct result of chronic alcohol abuse.

•Alcoholic cirrhosis is a debilitating disease that remains among the
top 10 causes of death worldwide.
Alcoholic Liver Disease and
Alcoholic Cirrhosis

•Alcoholic cirrhosis is an irreversible condition that has an estimated
frequency of 10% to 15% among people who consume more than
50 g of alcohol daily over a 10-year period.

•It is characterized by both steatosis and hepatitis, and fibrosis. If left
unchecked and untreated, inflammation of the liver certainly
produces hepatic fibrosis.

•The principal pathogenic process in the development of cirrhosis is
the progressive fibrotic changes that occur within the liver
parenchyma combined with the disruption of the normal hepatic
vasculature.
Alcohol and the Liver
•CIRRHOSIS

–The clinical and laboratory features of alcoholic
cirrhosis are largely similar to those seen in other
causes of cirrhosis

–one exception: affected patients may have
concurrent evidence of alcoholic hepatitis.
• increased ratio of serum AST to ALT,
•jaundice, alkaline phosphatase elevation,
•hematologic abnormalities may coexist with stigmata of
chronic liver disease.

Alcohol and the Liver
• long-term management of alcoholic liver
disease:
– importance of abstinence
– well nourished, and nutritional supplements
–During hospitalizations for decompensation of
alcoholic liver disease, aggressive nutritional
therapy should be instituted
–Complications of cirrhosis that arise in patients
with alcoholic liver disease should be sought and
treated
–end stage alcoholic liver disease should be
considered for liver transplantation


•Young patient admitted to the emergency for
–Jaundice
–confusion

•Labs:
–ALT 2000
–AST 1500
–Total Bilirubin 20
•Direct: 15

•Next step ??

•Abdominal ultra sound

•Other labs test?

•Physical exam

Fulminant hepatic failure

Fulminant hepatic failure
definition

•Rapid development of severe acute liver injury
with impaired function and encephalopathy in
previously normal liver or well compensated
liver disease

–Encephalopathy within 8wks previous healthy
liver

–Encephalopathy within 2 wks of developing
jaundice with previous underlying liver
Subfulminant hepatic failure
definition

•FHF> 8wks – 6 months

•FHF VS sub FHF
–Cerebral edema is common in FHF and rare in sub
FHF
–Renal failure and portal hypertension are more
frequently with sub FHF

Causes of Acute liver failure

Viruses
Hepatitis A, B, C, D, E
Cytomegalovirus
Epstein–Barr virus
Herpes simplex virus 1 and 2
Varicella-zoster virus
Adenovirus
Dengue virus
Medications
Acetaminophen
Anti-tuberculosis (Isoniazid, Rifampin, Pyrazinamide)
Statins
Non-steroidal anti-inflammatory drugs
Sulfa drugs
Phenytoin
Carbamazepine
MDMA (ecstasy)
Flucloxacillin
Ketoconazole
Nitrofurantoin
Immune checkpoint inhibitors
Idiosyncratic drug reactions
Genetic/Autoimmune
Wilson disease
Autoimmune hepatitis
Vascular
Budd–Chiari syndrome
Veno-occlusive disease
Ischemic hepatitis
Herbals/Nutritional Supplements
Multiple agents (Kava Kava, Hydroxycut, Ma Huang, etc.)
Dietary and weight loss supplements
Multivitamins
Toxins
Mushroom (most commonly Amanita phalloides)
Carbon tetrachloride
Yellow phosphorus
Infiltration
Breast cancer
Small-cell lung cancer
Lymphoma
Colon cancer
Melanoma
Multiple myeloma
Pregnancy-related
Acute fatty liver of pregnancy
HELLP syndrome
Pre-eclamptic liver rupture
Other
Sepsis
Partial hepatectomy
Heat stroke
Hemophagocytic lymphohistiocytosis
causes
•Major causes of fulminant hepatic failure
–A- Acetaminophene, hep A, autoimmune hepatitis
–B- Hepatitis B
–C- Hepatitis C, cryptogenic
–D- Hepatitis D, drug
–E- Esoteric causes, Wilson’s disease, Budd-Chiari
–F – Fatty infiltration, acute fatty liver of
pregnancy, Reye’s syndrome

48. –Alcoholic hepatitis is defined by both clinical and
pathologic criteria

•clinically in a patient with a history of heavy alcohol use
and compatible clinical and laboratory findings

•clinical and laboratory features are often adequate for
establishing the diagnosis
Alcohol and the Liver

•ALCOHOLIC HEPATITIS:

–History is essential: information includes:

•amount and duration of alcohol ingestion,

•the possible presence of risk factors for hepatitis B or C

•use of potentially hepatotoxic drugs

•knowledge of prior liver disease.
Loading…
Alcohol and the Liver

•ALCOHOLIC HEPATITIS:

–Presentations
•Asymptomatic (majority of cases)
–Hepatomegaly
–Biochemistry mildly abnormal
–Needs histology for confirmation
•Symptomatic (minority of cases)
–Liver failure

– laboratory features:
Alcohol and the Liver
•ALCOHOLIC HEPATITIS:
–Clinical manifestations
•symptoms at presentation are those with fatty liver but
some patients remain asymptomatic.

•The characteristic signs and symptoms of alcoholic
hepatitis are
–Fever
–Hepatomegaly
–Jaundice
–anorexia
•The presence of stigmata of chronic liver disease (spider
angiomata, palmar erythema, gynecomastia) suggest
advanced disease with underlying cirrhosis.
Alcohol and the Liver
• ALCOHOLIC HEPATITIS: Pathology

–Obligatory features include
•Liver cell necrosis
•Mallory bodies
•Infiltration by neutrophils
•Perivenular distribution of inflammation

–not essential, histologic features include:
•bridging necrosis,
•fatty change,
•bile duct proliferation,
•cholestasis,
•perivenular fibrosis.
Alcoholic Liver Disease and
Alcoholic Cirrhosis

•alcoholic cirrhosis, is defined as a condition in which there is
continuing fibrosis resulting in the subdivision of the liver into
nodules of proliferating hepatocytes surrounded by scar tissue as
the direct result of chronic alcohol abuse.

•Alcoholic cirrhosis is a debilitating disease that remains among the
top 10 causes of death worldwide.
Alcoholic Liver Disease and
Alcoholic Cirrhosis

•Alcoholic cirrhosis is an irreversible condition that has an estimated
frequency of 10% to 15% among people who consume more than
50 g of alcohol daily over a 10-year period.

•It is characterized by both steatosis and hepatitis, and fibrosis. If left
unchecked and untreated, inflammation of the liver certainly
produces hepatic fibrosis.

•The principal pathogenic process in the development of cirrhosis is
the progressive fibrotic changes that occur within the liver
parenchyma combined with the disruption of the normal hepatic
vasculature.
Alcohol and the Liver
•CIRRHOSIS

–The clinical and laboratory features of alcoholic
cirrhosis are largely similar to those seen in other
causes of cirrhosis

–one exception: affected patients may have
concurrent evidence of alcoholic hepatitis.
• increased ratio of serum AST to ALT,
•jaundice, alkaline phosphatase elevation,
•hematologic abnormalities may coexist with stigmata of
chronic liver disease.

Alcohol and the Liver
• long-term management of alcoholic liver
disease:
– importance of abstinence
– well nourished, and nutritional supplements
–During hospitalizations for decompensation of
alcoholic liver disease, aggressive nutritional
therapy should be instituted
–Complications of cirrhosis that arise in patients
with alcoholic liver disease should be sought and
treated
–end stage alcoholic liver disease should be
considered for liver transplantation


•Young patient admitted to the emergency for
–Jaundice
–confusion

•Labs:
–ALT 2000
–AST 1500
–Total Bilirubin 20
•Direct: 15

•Next step ??

•Abdominal ultra sound

•Other labs test?

•Physical exam

Fulminant hepatic failure

Fulminant hepatic failure
definition

•Rapid development of severe acute liver injury
with impaired function and encephalopathy in
previously normal liver or well compensated
liver disease

–Encephalopathy within 8wks previous healthy
liver

–Encephalopathy within 2 wks of developing
jaundice with previous underlying liver
Subfulminant hepatic failure
definition

•FHF> 8wks – 6 months

•FHF VS sub FHF
–Cerebral edema is common in FHF and rare in sub
FHF
–Renal failure and portal hypertension are more
frequently with sub FHF

Causes of Acute liver failure

Viruses
Hepatitis A, B, C, D, E
Cytomegalovirus
Epstein–Barr virus
Herpes simplex virus 1 and 2
Varicella-zoster virus
Adenovirus
Dengue virus
Medications
Acetaminophen
Anti-tuberculosis (Isoniazid, Rifampin, Pyrazinamide)
Statins
Non-steroidal anti-inflammatory drugs
Sulfa drugs
Phenytoin
Carbamazepine
MDMA (ecstasy)
Flucloxacillin
Ketoconazole
Nitrofurantoin
Immune checkpoint inhibitors
Idiosyncratic drug reactions
Genetic/Autoimmune
Wilson disease
Autoimmune hepatitis
Vascular
Budd–Chiari syndrome
Veno-occlusive disease
Ischemic hepatitis
Herbals/Nutritional Supplements
Multiple agents (Kava Kava, Hydroxycut, Ma Huang, etc.)
Dietary and weight loss supplements
Multivitamins
Toxins
Mushroom (most commonly Amanita phalloides)
Carbon tetrachloride
Yellow phosphorus
Infiltration
Breast cancer
Small-cell lung cancer
Lymphoma
Colon cancer
Melanoma
Multiple myeloma
Pregnancy-related
Acute fatty liver of pregnancy
HELLP syndrome
Pre-eclamptic liver rupture
Other
Sepsis
Partial hepatectomy
Heat stroke
Hemophagocytic lymphohistiocytosis
causes
•Major causes of fulminant hepatic failure
–A- Acetaminophene, hep A, autoimmune hepatitis
–B- Hepatitis B
–C- Hepatitis C, cryptogenic
–D- Hepatitis D, drug
–E- Esoteric causes, Wilson’s disease, Budd-Chiari
–F – Fatty infiltration, acute fatty liver of
pregnancy, Reye’s syndrome

49. –Alcoholic hepatitis is defined by both clinical and
pathologic criteria

•clinically in a patient with a history of heavy alcohol use
and compatible clinical and laboratory findings

•clinical and laboratory features are often adequate for
establishing the diagnosis
Alcohol and the Liver

•ALCOHOLIC HEPATITIS:

–History is essential: information includes:

•amount and duration of alcohol ingestion,

•the possible presence of risk factors for hepatitis B or C

•use of potentially hepatotoxic drugs

•knowledge of prior liver disease.
Loading…
Alcohol and the Liver

•ALCOHOLIC HEPATITIS:

–Presentations
•Asymptomatic (majority of cases)
–Hepatomegaly
–Biochemistry mildly abnormal
–Needs histology for confirmation
•Symptomatic (minority of cases)
–Liver failure

– laboratory features:
Alcohol and the Liver
•ALCOHOLIC HEPATITIS:
–Clinical manifestations
•symptoms at presentation are those with fatty liver but
some patients remain asymptomatic.

•The characteristic signs and symptoms of alcoholic
hepatitis are
–Fever
–Hepatomegaly
–Jaundice
–anorexia
•The presence of stigmata of chronic liver disease (spider
angiomata, palmar erythema, gynecomastia) suggest
advanced disease with underlying cirrhosis.
Alcohol and the Liver
• ALCOHOLIC HEPATITIS: Pathology

–Obligatory features include
•Liver cell necrosis
•Mallory bodies
•Infiltration by neutrophils
•Perivenular distribution of inflammation

–not essential, histologic features include:
•bridging necrosis,
•fatty change,
•bile duct proliferation,
•cholestasis,
•perivenular fibrosis.
Alcoholic Liver Disease and
Alcoholic Cirrhosis

•alcoholic cirrhosis, is defined as a condition in which there is
continuing fibrosis resulting in the subdivision of the liver into
nodules of proliferating hepatocytes surrounded by scar tissue as
the direct result of chronic alcohol abuse.

•Alcoholic cirrhosis is a debilitating disease that remains among the
top 10 causes of death worldwide.
Alcoholic Liver Disease and
Alcoholic Cirrhosis

•Alcoholic cirrhosis is an irreversible condition that has an estimated
frequency of 10% to 15% among people who consume more than
50 g of alcohol daily over a 10-year period.

•It is characterized by both steatosis and hepatitis, and fibrosis. If left
unchecked and untreated, inflammation of the liver certainly
produces hepatic fibrosis.

•The principal pathogenic process in the development of cirrhosis is
the progressive fibrotic changes that occur within the liver
parenchyma combined with the disruption of the normal hepatic
vasculature.
Alcohol and the Liver
•CIRRHOSIS

–The clinical and laboratory features of alcoholic
cirrhosis are largely similar to those seen in other
causes of cirrhosis

–one exception: affected patients may have
concurrent evidence of alcoholic hepatitis.
• increased ratio of serum AST to ALT,
•jaundice, alkaline phosphatase elevation,
•hematologic abnormalities may coexist with stigmata of
chronic liver disease.

Alcohol and the Liver
• long-term management of alcoholic liver
disease:
– importance of abstinence
– well nourished, and nutritional supplements
–During hospitalizations for decompensation of
alcoholic liver disease, aggressive nutritional
therapy should be instituted
–Complications of cirrhosis that arise in patients
with alcoholic liver disease should be sought and
treated
–end stage alcoholic liver disease should be
considered for liver transplantation


•Young patient admitted to the emergency for
–Jaundice
–confusion

•Labs:
–ALT 2000
–AST 1500
–Total Bilirubin 20
•Direct: 15

•Next step ??

•Abdominal ultra sound

•Other labs test?

•Physical exam

Fulminant hepatic failure

Fulminant hepatic failure
definition

•Rapid development of severe acute liver injury
with impaired function and encephalopathy in
previously normal liver or well compensated
liver disease

–Encephalopathy within 8wks previous healthy
liver

–Encephalopathy within 2 wks of developing
jaundice with previous underlying liver
Subfulminant hepatic failure
definition

•FHF> 8wks – 6 months

•FHF VS sub FHF
–Cerebral edema is common in FHF and rare in sub
FHF
–Renal failure and portal hypertension are more
frequently with sub FHF

Causes of Acute liver failure

Viruses
Hepatitis A, B, C, D, E
Cytomegalovirus
Epstein–Barr virus
Herpes simplex virus 1 and 2
Varicella-zoster virus
Adenovirus
Dengue virus
Medications
Acetaminophen
Anti-tuberculosis (Isoniazid, Rifampin, Pyrazinamide)
Statins
Non-steroidal anti-inflammatory drugs
Sulfa drugs
Phenytoin
Carbamazepine
MDMA (ecstasy)
Flucloxacillin
Ketoconazole
Nitrofurantoin
Immune checkpoint inhibitors
Idiosyncratic drug reactions
Genetic/Autoimmune
Wilson disease
Autoimmune hepatitis
Vascular
Budd–Chiari syndrome
Veno-occlusive disease
Ischemic hepatitis
Herbals/Nutritional Supplements
Multiple agents (Kava Kava, Hydroxycut, Ma Huang, etc.)
Dietary and weight loss supplements
Multivitamins
Toxins
Mushroom (most commonly Amanita phalloides)
Carbon tetrachloride
Yellow phosphorus
Infiltration
Breast cancer
Small-cell lung cancer
Lymphoma
Colon cancer
Melanoma
Multiple myeloma
Pregnancy-related
Acute fatty liver of pregnancy
HELLP syndrome
Pre-eclamptic liver rupture
Other
Sepsis
Partial hepatectomy
Heat stroke
Hemophagocytic lymphohistiocytosis
causes
•Major causes of fulminant hepatic failure
–A- Acetaminophene, hep A, autoimmune hepatitis
–B- Hepatitis B
–C- Hepatitis C, cryptogenic
–D- Hepatitis D, drug
–E- Esoteric causes, Wilson’s disease, Budd-Chiari
–F – Fatty infiltration, acute fatty liver of
pregnancy, Reye’s syndrome

50. –Alcoholic hepatitis is defined by both clinical and
pathologic criteria

•clinically in a patient with a history of heavy alcohol use
and compatible clinical and laboratory findings

•clinical and laboratory features are often adequate for
establishing the diagnosis
Alcohol and the Liver

•ALCOHOLIC HEPATITIS:

–History is essential: information includes:

•amount and duration of alcohol ingestion,

•the possible presence of risk factors for hepatitis B or C

•use of potentially hepatotoxic drugs

•knowledge of prior liver disease.
Loading…
Alcohol and the Liver

•ALCOHOLIC HEPATITIS:

–Presentations
•Asymptomatic (majority of cases)
–Hepatomegaly
–Biochemistry mildly abnormal
–Needs histology for confirmation
•Symptomatic (minority of cases)
–Liver failure

– laboratory features:
Alcohol and the Liver
•ALCOHOLIC HEPATITIS:
–Clinical manifestations
•symptoms at presentation are those with fatty liver but
some patients remain asymptomatic.

•The characteristic signs and symptoms of alcoholic
hepatitis are
–Fever
–Hepatomegaly
–Jaundice
–anorexia
•The presence of stigmata of chronic liver disease (spider
angiomata, palmar erythema, gynecomastia) suggest
advanced disease with underlying cirrhosis.
Alcohol and the Liver
• ALCOHOLIC HEPATITIS: Pathology

–Obligatory features include
•Liver cell necrosis
•Mallory bodies
•Infiltration by neutrophils
•Perivenular distribution of inflammation

–not essential, histologic features include:
•bridging necrosis,
•fatty change,
•bile duct proliferation,
•cholestasis,
•perivenular fibrosis.
Alcoholic Liver Disease and
Alcoholic Cirrhosis

•alcoholic cirrhosis, is defined as a condition in which there is
continuing fibrosis resulting in the subdivision of the liver into
nodules of proliferating hepatocytes surrounded by scar tissue as
the direct result of chronic alcohol abuse.

•Alcoholic cirrhosis is a debilitating disease that remains among the
top 10 causes of death worldwide.
Alcoholic Liver Disease and
Alcoholic Cirrhosis

•Alcoholic cirrhosis is an irreversible condition that has an estimated
frequency of 10% to 15% among people who consume more than
50 g of alcohol daily over a 10-year period.

•It is characterized by both steatosis and hepatitis, and fibrosis. If left
unchecked and untreated, inflammation of the liver certainly
produces hepatic fibrosis.

•The principal pathogenic process in the development of cirrhosis is
the progressive fibrotic changes that occur within the liver
parenchyma combined with the disruption of the normal hepatic
vasculature.
Alcohol and the Liver
•CIRRHOSIS

–The clinical and laboratory features of alcoholic
cirrhosis are largely similar to those seen in other
causes of cirrhosis

–one exception: affected patients may have
concurrent evidence of alcoholic hepatitis.
• increased ratio of serum AST to ALT,
•jaundice, alkaline phosphatase elevation,
•hematologic abnormalities may coexist with stigmata of
chronic liver disease.

Alcohol and the Liver
• long-term management of alcoholic liver
disease:
– importance of abstinence
– well nourished, and nutritional supplements
–During hospitalizations for decompensation of
alcoholic liver disease, aggressive nutritional
therapy should be instituted
–Complications of cirrhosis that arise in patients
with alcoholic liver disease should be sought and
treated
–end stage alcoholic liver disease should be
considered for liver transplantation


•Young patient admitted to the emergency for
–Jaundice
–confusion

•Labs:
–ALT 2000
–AST 1500
–Total Bilirubin 20
•Direct: 15

•Next step ??

•Abdominal ultra sound

•Other labs test?

•Physical exam

Fulminant hepatic failure

Fulminant hepatic failure
definition

•Rapid development of severe acute liver injury
with impaired function and encephalopathy in
previously normal liver or well compensated
liver disease

–Encephalopathy within 8wks previous healthy
liver

–Encephalopathy within 2 wks of developing
jaundice with previous underlying liver
Subfulminant hepatic failure
definition

•FHF> 8wks – 6 months

•FHF VS sub FHF
–Cerebral edema is common in FHF and rare in sub
FHF
–Renal failure and portal hypertension are more
frequently with sub FHF

Causes of Acute liver failure

Viruses
Hepatitis A, B, C, D, E
Cytomegalovirus
Epstein–Barr virus
Herpes simplex virus 1 and 2
Varicella-zoster virus
Adenovirus
Dengue virus
Medications
Acetaminophen
Anti-tuberculosis (Isoniazid, Rifampin, Pyrazinamide)
Statins
Non-steroidal anti-inflammatory drugs
Sulfa drugs
Phenytoin
Carbamazepine
MDMA (ecstasy)
Flucloxacillin
Ketoconazole
Nitrofurantoin
Immune checkpoint inhibitors
Idiosyncratic drug reactions
Genetic/Autoimmune
Wilson disease
Autoimmune hepatitis
Vascular
Budd–Chiari syndrome
Veno-occlusive disease
Ischemic hepatitis
Herbals/Nutritional Supplements
Multiple agents (Kava Kava, Hydroxycut, Ma Huang, etc.)
Dietary and weight loss supplements
Multivitamins
Toxins
Mushroom (most commonly Amanita phalloides)
Carbon tetrachloride
Yellow phosphorus
Infiltration
Breast cancer
Small-cell lung cancer
Lymphoma
Colon cancer
Melanoma
Multiple myeloma
Pregnancy-related
Acute fatty liver of pregnancy
HELLP syndrome
Pre-eclamptic liver rupture
Other
Sepsis
Partial hepatectomy
Heat stroke
Hemophagocytic lymphohistiocytosis
causes
•Major causes of fulminant hepatic failure
–A- Acetaminophene, hep A, autoimmune hepatitis
–B- Hepatitis B
–C- Hepatitis C, cryptogenic
–D- Hepatitis D, drug
–E- Esoteric causes, Wilson’s disease, Budd-Chiari
–F – Fatty infiltration, acute fatty liver of
pregnancy, Reye’s syndrome

51. –Alcoholic hepatitis is defined by both clinical and
pathologic criteria

•clinically in a patient with a history of heavy alcohol use
and compatible clinical and laboratory findings

•clinical and laboratory features are often adequate for
establishing the diagnosis
Alcohol and the Liver

•ALCOHOLIC HEPATITIS:

–History is essential: information includes:

•amount and duration of alcohol ingestion,

•the possible presence of risk factors for hepatitis B or C

•use of potentially hepatotoxic drugs

•knowledge of prior liver disease.
Loading…
Alcohol and the Liver

•ALCOHOLIC HEPATITIS:

–Presentations
•Asymptomatic (majority of cases)
–Hepatomegaly
–Biochemistry mildly abnormal
–Needs histology for confirmation
•Symptomatic (minority of cases)
–Liver failure

– laboratory features:
Alcohol and the Liver
•ALCOHOLIC HEPATITIS:
–Clinical manifestations
•symptoms at presentation are those with fatty liver but
some patients remain asymptomatic.

•The characteristic signs and symptoms of alcoholic
hepatitis are
–Fever
–Hepatomegaly
–Jaundice
–anorexia
•The presence of stigmata of chronic liver disease (spider
angiomata, palmar erythema, gynecomastia) suggest
advanced disease with underlying cirrhosis.
Alcohol and the Liver
• ALCOHOLIC HEPATITIS: Pathology

–Obligatory features include
•Liver cell necrosis
•Mallory bodies
•Infiltration by neutrophils
•Perivenular distribution of inflammation

–not essential, histologic features include:
•bridging necrosis,
•fatty change,
•bile duct proliferation,
•cholestasis,
•perivenular fibrosis.
Alcoholic Liver Disease and
Alcoholic Cirrhosis

•alcoholic cirrhosis, is defined as a condition in which there is
continuing fibrosis resulting in the subdivision of the liver into
nodules of proliferating hepatocytes surrounded by scar tissue as
the direct result of chronic alcohol abuse.

•Alcoholic cirrhosis is a debilitating disease that remains among the
top 10 causes of death worldwide.
Alcoholic Liver Disease and
Alcoholic Cirrhosis

•Alcoholic cirrhosis is an irreversible condition that has an estimated
frequency of 10% to 15% among people who consume more than
50 g of alcohol daily over a 10-year period.

•It is characterized by both steatosis and hepatitis, and fibrosis. If left
unchecked and untreated, inflammation of the liver certainly
produces hepatic fibrosis.

•The principal pathogenic process in the development of cirrhosis is
the progressive fibrotic changes that occur within the liver
parenchyma combined with the disruption of the normal hepatic
vasculature.
Alcohol and the Liver
•CIRRHOSIS

–The clinical and laboratory features of alcoholic
cirrhosis are largely similar to those seen in other
causes of cirrhosis

–one exception: affected patients may have
concurrent evidence of alcoholic hepatitis.
• increased ratio of serum AST to ALT,
•jaundice, alkaline phosphatase elevation,
•hematologic abnormalities may coexist with stigmata of
chronic liver disease.

Alcohol and the Liver
• long-term management of alcoholic liver
disease:
– importance of abstinence
– well nourished, and nutritional supplements
–During hospitalizations for decompensation of
alcoholic liver disease, aggressive nutritional
therapy should be instituted
–Complications of cirrhosis that arise in patients
with alcoholic liver disease should be sought and
treated
–end stage alcoholic liver disease should be
considered for liver transplantation


•Young patient admitted to the emergency for
–Jaundice
–confusion

•Labs:
–ALT 2000
–AST 1500
–Total Bilirubin 20
•Direct: 15

•Next step ??

•Abdominal ultra sound

•Other labs test?

•Physical exam

Fulminant hepatic failure

Fulminant hepatic failure
definition

•Rapid development of severe acute liver injury
with impaired function and encephalopathy in
previously normal liver or well compensated
liver disease

–Encephalopathy within 8wks previous healthy
liver

–Encephalopathy within 2 wks of developing
jaundice with previous underlying liver
Subfulminant hepatic failure
definition

•FHF> 8wks – 6 months

•FHF VS sub FHF
–Cerebral edema is common in FHF and rare in sub
FHF
–Renal failure and portal hypertension are more
frequently with sub FHF

Causes of Acute liver failure

Viruses
Hepatitis A, B, C, D, E
Cytomegalovirus
Epstein–Barr virus
Herpes simplex virus 1 and 2
Varicella-zoster virus
Adenovirus
Dengue virus
Medications
Acetaminophen
Anti-tuberculosis (Isoniazid, Rifampin, Pyrazinamide)
Statins
Non-steroidal anti-inflammatory drugs
Sulfa drugs
Phenytoin
Carbamazepine
MDMA (ecstasy)
Flucloxacillin
Ketoconazole
Nitrofurantoin
Immune checkpoint inhibitors
Idiosyncratic drug reactions
Genetic/Autoimmune
Wilson disease
Autoimmune hepatitis
Vascular
Budd–Chiari syndrome
Veno-occlusive disease
Ischemic hepatitis
Herbals/Nutritional Supplements
Multiple agents (Kava Kava, Hydroxycut, Ma Huang, etc.)
Dietary and weight loss supplements
Multivitamins
Toxins
Mushroom (most commonly Amanita phalloides)
Carbon tetrachloride
Yellow phosphorus
Infiltration
Breast cancer
Small-cell lung cancer
Lymphoma
Colon cancer
Melanoma
Multiple myeloma
Pregnancy-related
Acute fatty liver of pregnancy
HELLP syndrome
Pre-eclamptic liver rupture
Other
Sepsis
Partial hepatectomy
Heat stroke
Hemophagocytic lymphohistiocytosis
causes
•Major causes of fulminant hepatic failure
–A- Acetaminophene, hep A, autoimmune hepatitis
–B- Hepatitis B
–C- Hepatitis C, cryptogenic
–D- Hepatitis D, drug
–E- Esoteric causes, Wilson’s disease, Budd-Chiari
–F – Fatty infiltration, acute fatty liver of
pregnancy, Reye’s syndrome

52. –Alcoholic hepatitis is defined by both clinical and
pathologic criteria

•clinically in a patient with a history of heavy alcohol use
and compatible clinical and laboratory findings

•clinical and laboratory features are often adequate for
establishing the diagnosis
Alcohol and the Liver

•ALCOHOLIC HEPATITIS:

–History is essential: information includes:

•amount and duration of alcohol ingestion,

•the possible presence of risk factors for hepatitis B or C

•use of potentially hepatotoxic drugs

•knowledge of prior liver disease.
Loading…
Alcohol and the Liver

•ALCOHOLIC HEPATITIS:

–Presentations
•Asymptomatic (majority of cases)
–Hepatomegaly
–Biochemistry mildly abnormal
–Needs histology for confirmation
•Symptomatic (minority of cases)
–Liver failure

– laboratory features:
Alcohol and the Liver
•ALCOHOLIC HEPATITIS:
–Clinical manifestations
•symptoms at presentation are those with fatty liver but
some patients remain asymptomatic.

•The characteristic signs and symptoms of alcoholic
hepatitis are
–Fever
–Hepatomegaly
–Jaundice
–anorexia
•The presence of stigmata of chronic liver disease (spider
angiomata, palmar erythema, gynecomastia) suggest
advanced disease with underlying cirrhosis.
Alcohol and the Liver
• ALCOHOLIC HEPATITIS: Pathology

–Obligatory features include
•Liver cell necrosis
•Mallory bodies
•Infiltration by neutrophils
•Perivenular distribution of inflammation

–not essential, histologic features include:
•bridging necrosis,
•fatty change,
•bile duct proliferation,
•cholestasis,
•perivenular fibrosis.
Alcoholic Liver Disease and
Alcoholic Cirrhosis

•alcoholic cirrhosis, is defined as a condition in which there is
continuing fibrosis resulting in the subdivision of the liver into
nodules of proliferating hepatocytes surrounded by scar tissue as
the direct result of chronic alcohol abuse.

•Alcoholic cirrhosis is a debilitating disease that remains among the
top 10 causes of death worldwide.
Alcoholic Liver Disease and
Alcoholic Cirrhosis

•Alcoholic cirrhosis is an irreversible condition that has an estimated
frequency of 10% to 15% among people who consume more than
50 g of alcohol daily over a 10-year period.

•It is characterized by both steatosis and hepatitis, and fibrosis. If left
unchecked and untreated, inflammation of the liver certainly
produces hepatic fibrosis.

•The principal pathogenic process in the development of cirrhosis is
the progressive fibrotic changes that occur within the liver
parenchyma combined with the disruption of the normal hepatic
vasculature.
Alcohol and the Liver
•CIRRHOSIS

–The clinical and laboratory features of alcoholic
cirrhosis are largely similar to those seen in other
causes of cirrhosis

–one exception: affected patients may have
concurrent evidence of alcoholic hepatitis.
• increased ratio of serum AST to ALT,
•jaundice, alkaline phosphatase elevation,
•hematologic abnormalities may coexist with stigmata of
chronic liver disease.

Alcohol and the Liver
• long-term management of alcoholic liver
disease:
– importance of abstinence
– well nourished, and nutritional supplements
–During hospitalizations for decompensation of
alcoholic liver disease, aggressive nutritional
therapy should be instituted
–Complications of cirrhosis that arise in patients
with alcoholic liver disease should be sought and
treated
–end stage alcoholic liver disease should be
considered for liver transplantation


•Young patient admitted to the emergency for
–Jaundice
–confusion

•Labs:
–ALT 2000
–AST 1500
–Total Bilirubin 20
•Direct: 15

•Next step ??

•Abdominal ultra sound

•Other labs test?

•Physical exam

Fulminant hepatic failure

Fulminant hepatic failure
definition

•Rapid development of severe acute liver injury
with impaired function and encephalopathy in
previously normal liver or well compensated
liver disease

–Encephalopathy within 8wks previous healthy
liver

–Encephalopathy within 2 wks of developing
jaundice with previous underlying liver
Subfulminant hepatic failure
definition

•FHF> 8wks – 6 months

•FHF VS sub FHF
–Cerebral edema is common in FHF and rare in sub
FHF
–Renal failure and portal hypertension are more
frequently with sub FHF

Causes of Acute liver failure

Viruses
Hepatitis A, B, C, D, E
Cytomegalovirus
Epstein–Barr virus
Herpes simplex virus 1 and 2
Varicella-zoster virus
Adenovirus
Dengue virus
Medications
Acetaminophen
Anti-tuberculosis (Isoniazid, Rifampin, Pyrazinamide)
Statins
Non-steroidal anti-inflammatory drugs
Sulfa drugs
Phenytoin
Carbamazepine
MDMA (ecstasy)
Flucloxacillin
Ketoconazole
Nitrofurantoin
Immune checkpoint inhibitors
Idiosyncratic drug reactions
Genetic/Autoimmune
Wilson disease
Autoimmune hepatitis
Vascular
Budd–Chiari syndrome
Veno-occlusive disease
Ischemic hepatitis
Herbals/Nutritional Supplements
Multiple agents (Kava Kava, Hydroxycut, Ma Huang, etc.)
Dietary and weight loss supplements
Multivitamins
Toxins
Mushroom (most commonly Amanita phalloides)
Carbon tetrachloride
Yellow phosphorus
Infiltration
Breast cancer
Small-cell lung cancer
Lymphoma
Colon cancer
Melanoma
Multiple myeloma
Pregnancy-related
Acute fatty liver of pregnancy
HELLP syndrome
Pre-eclamptic liver rupture
Other
Sepsis
Partial hepatectomy
Heat stroke
Hemophagocytic lymphohistiocytosis
causes
•Major causes of fulminant hepatic failure
–A- Acetaminophene, hep A, autoimmune hepatitis
–B- Hepatitis B
–C- Hepatitis C, cryptogenic
–D- Hepatitis D, drug
–E- Esoteric causes, Wilson’s disease, Budd-Chiari
–F – Fatty infiltration, acute fatty liver of
pregnancy, Reye’s syndrome

53. –Alcoholic hepatitis is defined by both clinical and
pathologic criteria

•clinically in a patient with a history of heavy alcohol use
and compatible clinical and laboratory findings

•clinical and laboratory features are often adequate for
establishing the diagnosis
Alcohol and the Liver

•ALCOHOLIC HEPATITIS:

–History is essential: information includes:

•amount and duration of alcohol ingestion,

•the possible presence of risk factors for hepatitis B or C

•use of potentially hepatotoxic drugs

•knowledge of prior liver disease.
Loading…
Alcohol and the Liver

•ALCOHOLIC HEPATITIS:

–Presentations
•Asymptomatic (majority of cases)
–Hepatomegaly
–Biochemistry mildly abnormal
–Needs histology for confirmation
•Symptomatic (minority of cases)
–Liver failure

– laboratory features:
Alcohol and the Liver
•ALCOHOLIC HEPATITIS:
–Clinical manifestations
•symptoms at presentation are those with fatty liver but
some patients remain asymptomatic.

•The characteristic signs and symptoms of alcoholic
hepatitis are
–Fever
–Hepatomegaly
–Jaundice
–anorexia
•The presence of stigmata of chronic liver disease (spider
angiomata, palmar erythema, gynecomastia) suggest
advanced disease with underlying cirrhosis.
Alcohol and the Liver
• ALCOHOLIC HEPATITIS: Pathology

–Obligatory features include
•Liver cell necrosis
•Mallory bodies
•Infiltration by neutrophils
•Perivenular distribution of inflammation

–not essential, histologic features include:
•bridging necrosis,
•fatty change,
•bile duct proliferation,
•cholestasis,
•perivenular fibrosis.
Alcoholic Liver Disease and
Alcoholic Cirrhosis

•alcoholic cirrhosis, is defined as a condition in which there is
continuing fibrosis resulting in the subdivision of the liver into
nodules of proliferating hepatocytes surrounded by scar tissue as
the direct result of chronic alcohol abuse.

•Alcoholic cirrhosis is a debilitating disease that remains among the
top 10 causes of death worldwide.
Alcoholic Liver Disease and
Alcoholic Cirrhosis

•Alcoholic cirrhosis is an irreversible condition that has an estimated
frequency of 10% to 15% among people who consume more than
50 g of alcohol daily over a 10-year period.

•It is characterized by both steatosis and hepatitis, and fibrosis. If left
unchecked and untreated, inflammation of the liver certainly
produces hepatic fibrosis.

•The principal pathogenic process in the development of cirrhosis is
the progressive fibrotic changes that occur within the liver
parenchyma combined with the disruption of the normal hepatic
vasculature.
Alcohol and the Liver
•CIRRHOSIS

–The clinical and laboratory features of alcoholic
cirrhosis are largely similar to those seen in other
causes of cirrhosis

–one exception: affected patients may have
concurrent evidence of alcoholic hepatitis.
• increased ratio of serum AST to ALT,
•jaundice, alkaline phosphatase elevation,
•hematologic abnormalities may coexist with stigmata of
chronic liver disease.

Alcohol and the Liver
• long-term management of alcoholic liver
disease:
– importance of abstinence
– well nourished, and nutritional supplements
–During hospitalizations for decompensation of
alcoholic liver disease, aggressive nutritional
therapy should be instituted
–Complications of cirrhosis that arise in patients
with alcoholic liver disease should be sought and
treated
–end stage alcoholic liver disease should be
considered for liver transplantation


•Young patient admitted to the emergency for
–Jaundice
–confusion

•Labs:
–ALT 2000
–AST 1500
–Total Bilirubin 20
•Direct: 15

•Next step ??

•Abdominal ultra sound

•Other labs test?

•Physical exam

Fulminant hepatic failure

Fulminant hepatic failure
definition

•Rapid development of severe acute liver injury
with impaired function and encephalopathy in
previously normal liver or well compensated
liver disease

–Encephalopathy within 8wks previous healthy
liver

–Encephalopathy within 2 wks of developing
jaundice with previous underlying liver
Subfulminant hepatic failure
definition

•FHF> 8wks – 6 months

•FHF VS sub FHF
–Cerebral edema is common in FHF and rare in sub
FHF
–Renal failure and portal hypertension are more
frequently with sub FHF

Causes of Acute liver failure

Viruses
Hepatitis A, B, C, D, E
Cytomegalovirus
Epstein–Barr virus
Herpes simplex virus 1 and 2
Varicella-zoster virus
Adenovirus
Dengue virus
Medications
Acetaminophen
Anti-tuberculosis (Isoniazid, Rifampin, Pyrazinamide)
Statins
Non-steroidal anti-inflammatory drugs
Sulfa drugs
Phenytoin
Carbamazepine
MDMA (ecstasy)
Flucloxacillin
Ketoconazole
Nitrofurantoin
Immune checkpoint inhibitors
Idiosyncratic drug reactions
Genetic/Autoimmune
Wilson disease
Autoimmune hepatitis
Vascular
Budd–Chiari syndrome
Veno-occlusive disease
Ischemic hepatitis
Herbals/Nutritional Supplements
Multiple agents (Kava Kava, Hydroxycut, Ma Huang, etc.)
Dietary and weight loss supplements
Multivitamins
Toxins
Mushroom (most commonly Amanita phalloides)
Carbon tetrachloride
Yellow phosphorus
Infiltration
Breast cancer
Small-cell lung cancer
Lymphoma
Colon cancer
Melanoma
Multiple myeloma
Pregnancy-related
Acute fatty liver of pregnancy
HELLP syndrome
Pre-eclamptic liver rupture
Other
Sepsis
Partial hepatectomy
Heat stroke
Hemophagocytic lymphohistiocytosis
causes
•Major causes of fulminant hepatic failure
–A- Acetaminophene, hep A, autoimmune hepatitis
–B- Hepatitis B
–C- Hepatitis C, cryptogenic
–D- Hepatitis D, drug
–E- Esoteric causes, Wilson’s disease, Budd-Chiari
–F – Fatty infiltration, acute fatty liver of
pregnancy, Reye’s syndrome
causes
•Hepatitis viruses
–Hepatitis A most common acute viral hepatitis but
rare for acute infection to progress to ALF
–Hepatitis B most common viral cause ALF
•Drug and toxins
–Acetaminophen, alcohol, Amiodarone, halothane,
isoniazid, methyldopa, NSAIDS, phenytoin,
rifampicin, sufonamides, tetracycline, tricyclic
antidepressants, valpoic acid
causes
•Vascular
–Portal vein thrombosis
–Budd-Chiari syndrome
–Veno-occlusive disease
–Ischemic hepatitis
•Metabolic
–Wilson’s disease
–Acute fatty liver of pregnancy
–Reye’s syndrome
causes
•Miscellaneous
–Malignant infiltration of the liver
–Heat stroke
–Sepsis
–Autoimmune hepatitis
Acetaminophen toxicity
Very high AST and ALT (often >3500 IU/L)
High INR
Low bilirubin
Ischemic hepatic injury
Very high AST and ALT (25–250 times of upper limit of normal)
Elevated serum LDH
Hepatitis B virus
Aminotransferase levels: 1000–2000 IU/L
ALT usually > AST
Wilson disease
Coombs-negative hemolytic anemia
Aminotransferase levels <2000 IU/L
AST/ALT ratio >2
Markedly low ALP (<40 IU/L)
ALP/total bilirubin ratio <4
Rapidly progressive renal failure
Low uric acid levels
Acute fatty liver of pregnancy/HELLP syndrome
Aminotransferase levels <1000 IU/L
Elevated bilirubin
Low platelet count
Herpes simplex virus
Markedly elevated aminotransferases
Leukopenia
Low bilirubin
Reye syndrome/Valproate or doxycycline toxicity Minor to moderate elevations in aminotransferase and bilirubin levels
Sign and symptom
•Acute liver failure
–Nonspecific symptoms
–Malaise
–Nausea
–Jaundice
–Ecchymoses
–Etc…
FHF complication
•Hepatic encephalopathy
•Cerebral edema
•Sepsis
•Renal failure
•Circulatory dysfunction
•Coagulopathy
•Gastrointestinal bleeding
•Pulmonary complication
•Metabolic disturbance, metabolic acidosis,
hypoglycemia, hypophosphatemia
FHF
Laboratory
•Hematology
–CBC, coagulation
•Biochemistry
–Blood glucose, BUN, creatinine, electrolyte, LFT
•Blood gas
•Virological markers
–Hepatitis profiles (A, B, C, delta)
•Microbiology
–Hemoculture
–Sputum/urine culture
Treatment
•Specific treatment
–Liver transplantation (stage 3 and 4)
•Complication treatment
–Hepatic encephalopathy
–Cerebral edema
–Sepsis
–Renal failure
–Circulatory dysfunction
–Coagulopathy
–Gastrointestinal bleeding
–Pulmonary complication
Complication treatment
•Hepatic encephalopathy
•↑ amonia WITHIN THE GUT LUMEN

•Concept
–Ammonia ↓
–Precipitating factors↓

•Restrict protein diet: 40 – 70 g/day
•Non-absorbable disaccharides: laculose
•Antibiotic: rifaximin, neomycin,
Complication treatment
•Cerebral edema
–Astrocyte edema
–Brainstem herniation, most causes of death
–Neurologic manifestations hypertonic, hyperflexia,
and altered pupillary responses

–Treatment:
•Elevated head position
•Manitol 0.5-1g/kg
ISCHEMIC HEPATITIS
(SHOCK LIVER, HYPOXIC
HEPATITIS)

ISCHEMIC HEPATITIS


•Ischemic hepatitis refers to diffuse hepatic
injury resulting from acute hypoperfusion



•Many cases of ischemic hepatitis occur in the
setting of congestive heart failure
ISCHEMIC HEPATITIS

•Clinical manifestations
–Any cause of shock or hemodynamic instability
can cause ischemic injury to the liver

–Ischemic injury can also be caused by focal
interruption of the hepatic blood supply

–The hemodynamic insult is usually apparent
clinically before evidence of liver injury appears
ISCHEMIC HEPATITIS

–Ischemic hepatitis is usually first detected because
of elevations in liver biochemical tests following a
hypotensive episode.

–Rare patients have symptoms suggesting acute
hepatitis, including nausea, vomiting, anorexia,
malaise, and right upper quadrant pain

–ischemia should always be considered in the
differential diagnosis of acute hepatitis, along with
more common causes such as viral infection,
ISCHEMIC HEPATITIS
•typical pattern of liver biochemical tests
consists of:

–rapid rise in serum aminotransferase levels
associated with an early massive rise in lactate
dehydrogenase (LDH) levels

–Peak aminotransferase levels are typically 25 to
250 times the upper limit of normal and are
reached within one to three days of the
hemodynamic insult

ISCHEMIC HEPATITIS
•Diagnosis

– There are relatively few causes of liver injury that
result in the striking increases in aminotransferase
levels

–Besides ischemic hepatitis, the most common are
acute viral hepatitis and acute drug- or toxin-
induced liver injury
ISCHEMIC HEPATITIS
•Pathology

–The histologic hallmark of ischemic hepatitis is
necrosis of hepatocytes
–associated with a variable degree of architectural
collapse around the central vein, depending upon
the duration and extent of ischemia

–There are characteristically few inflammatory cells
ISCHEMIC HEPATITIS
•Management
– aimed at restoring cardiac output and reversing
the underlying cause of hemodynamic instability.

•Prognosis:
– Ischemic hepatitis is nearly always benign and
self-limited.
–The severity of the liver injury correlates with the
duration and extent of the hemodynamic
compromise.
–Prognosis is mostly related to the severity of the
Drugs induced hepatitis

Drugs induced hepatitis

•Drug hepatotoxicity is the most common cause
of fulminant liver failure in the United States

•Hepatotoxicity can occur with many drugs by a
variety of mechanisms.
Drugs induced hepatitis

SPECTRUM OF DRUG-INDUCED
HEPATOTOXICITY
–A variety of clinical presentations may be seen in
patients who develop drug hepatotoxicity, ranging
from
•asymptomatic mild biochemical abnormalities to an
acute illness with jaundice that resembles viral hepatitis
Drugs induced hepatitis
SPECTRUM OF DRUG-INDUCED HEPATOTOXICITY
- Subclinical
- Acute hepatic injury
- Cytotoxic
- Cholestatic
- mixed patterns
- Steatosis
- Chronic hepatic injury
- Chronic hepatitis
- steatosis
- fibrosis and cirrhosis
- Vascular disease
- granulomatous disease
- Neoplasia
Drugs induced hepatitis
Subclinical

–Many drugs can induce asymptomatic elevations
in liver enzymes without producing overt clinical
disease
•antibiotics, antidepressants, antihyperlipidemics,
sulfonamides, salicylates, sulfonylureas, and quinidine

–Most elevations are benign and resolve once the
offending agent has been discontinued.
Drugs induced hepatitis
•Acute hepatic injury

–Cytotoxic
•hepatocellular injury is similar to that seen in viral
hepatitis and includes necrosis, steatosis, and cellular
degeneration.
• acetaminophen, phenytoin, methyldopa, diclofenac

–Cholestatic
•resembles extrahepatic obstructive jaundice
•chlorpromazine, trimethoprim-sulfamethoxazole,
rifampin, erythromycin, amiodarone
Drugs induced hepatitis
•Acute hepatic injury

–Mixed patterns
•often seen in patients with hepatotoxicity due to phenytoin
•Such patients may be at increased risk to develop chronic liver
disease compared with other forms of hepatotoxicity

– Steatosis
• Drug-induced acute steatosis is uncommon and occurs less often
than chronic steatosis.
•acute steatosis tends to be microvesicular
•tetracycline, amiodarone, piroxicam
Drugs induced hepatitis
•Chronic hepatic injury

54. causes
•Hepatitis viruses
–Hepatitis A most common acute viral hepatitis but
rare for acute infection to progress to ALF
–Hepatitis B most common viral cause ALF
•Drug and toxins
–Acetaminophen, alcohol, Amiodarone, halothane,
isoniazid, methyldopa, NSAIDS, phenytoin,
rifampicin, sufonamides, tetracycline, tricyclic
antidepressants, valpoic acid
causes
•Vascular
–Portal vein thrombosis
–Budd-Chiari syndrome
–Veno-occlusive disease
–Ischemic hepatitis
•Metabolic
–Wilson’s disease
–Acute fatty liver of pregnancy
–Reye’s syndrome
causes
•Miscellaneous
–Malignant infiltration of the liver
–Heat stroke
–Sepsis
–Autoimmune hepatitis
Acetaminophen toxicity
Very high AST and ALT (often >3500 IU/L)
High INR
Low bilirubin
Ischemic hepatic injury
Very high AST and ALT (25–250 times of upper limit of normal)
Elevated serum LDH
Hepatitis B virus
Aminotransferase levels: 1000–2000 IU/L
ALT usually > AST
Wilson disease
Coombs-negative hemolytic anemia
Aminotransferase levels <2000 IU/L
AST/ALT ratio >2
Markedly low ALP (<40 IU/L)
ALP/total bilirubin ratio <4
Rapidly progressive renal failure
Low uric acid levels
Acute fatty liver of pregnancy/HELLP syndrome
Aminotransferase levels <1000 IU/L
Elevated bilirubin
Low platelet count
Herpes simplex virus
Markedly elevated aminotransferases
Leukopenia
Low bilirubin
Reye syndrome/Valproate or doxycycline toxicity Minor to moderate elevations in aminotransferase and bilirubin levels
Sign and symptom
•Acute liver failure
–Nonspecific symptoms
–Malaise
–Nausea
–Jaundice
–Ecchymoses
–Etc…
FHF complication
•Hepatic encephalopathy
•Cerebral edema
•Sepsis
•Renal failure
•Circulatory dysfunction
•Coagulopathy
•Gastrointestinal bleeding
•Pulmonary complication
•Metabolic disturbance, metabolic acidosis,
hypoglycemia, hypophosphatemia
FHF
Laboratory
•Hematology
–CBC, coagulation
•Biochemistry
–Blood glucose, BUN, creatinine, electrolyte, LFT
•Blood gas
•Virological markers
–Hepatitis profiles (A, B, C, delta)
•Microbiology
–Hemoculture
–Sputum/urine culture
Treatment
•Specific treatment
–Liver transplantation (stage 3 and 4)
•Complication treatment
–Hepatic encephalopathy
–Cerebral edema
–Sepsis
–Renal failure
–Circulatory dysfunction
–Coagulopathy
–Gastrointestinal bleeding
–Pulmonary complication
Complication treatment
•Hepatic encephalopathy
•↑ amonia WITHIN THE GUT LUMEN

•Concept
–Ammonia ↓
–Precipitating factors↓

•Restrict protein diet: 40 – 70 g/day
•Non-absorbable disaccharides: laculose
•Antibiotic: rifaximin, neomycin,
Complication treatment
•Cerebral edema
–Astrocyte edema
–Brainstem herniation, most causes of death
–Neurologic manifestations hypertonic, hyperflexia,
and altered pupillary responses

–Treatment:
•Elevated head position
•Manitol 0.5-1g/kg
ISCHEMIC HEPATITIS
(SHOCK LIVER, HYPOXIC
HEPATITIS)

ISCHEMIC HEPATITIS


•Ischemic hepatitis refers to diffuse hepatic
injury resulting from acute hypoperfusion



•Many cases of ischemic hepatitis occur in the
setting of congestive heart failure
ISCHEMIC HEPATITIS

•Clinical manifestations
–Any cause of shock or hemodynamic instability
can cause ischemic injury to the liver

–Ischemic injury can also be caused by focal
interruption of the hepatic blood supply

–The hemodynamic insult is usually apparent
clinically before evidence of liver injury appears
ISCHEMIC HEPATITIS

–Ischemic hepatitis is usually first detected because
of elevations in liver biochemical tests following a
hypotensive episode.

–Rare patients have symptoms suggesting acute
hepatitis, including nausea, vomiting, anorexia,
malaise, and right upper quadrant pain

–ischemia should always be considered in the
differential diagnosis of acute hepatitis, along with
more common causes such as viral infection,
ISCHEMIC HEPATITIS
•typical pattern of liver biochemical tests
consists of:

–rapid rise in serum aminotransferase levels
associated with an early massive rise in lactate
dehydrogenase (LDH) levels

–Peak aminotransferase levels are typically 25 to
250 times the upper limit of normal and are
reached within one to three days of the
hemodynamic insult

ISCHEMIC HEPATITIS
•Diagnosis

– There are relatively few causes of liver injury that
result in the striking increases in aminotransferase
levels

–Besides ischemic hepatitis, the most common are
acute viral hepatitis and acute drug- or toxin-
induced liver injury
ISCHEMIC HEPATITIS
•Pathology

–The histologic hallmark of ischemic hepatitis is
necrosis of hepatocytes
–associated with a variable degree of architectural
collapse around the central vein, depending upon
the duration and extent of ischemia

–There are characteristically few inflammatory cells
ISCHEMIC HEPATITIS
•Management
– aimed at restoring cardiac output and reversing
the underlying cause of hemodynamic instability.

•Prognosis:
– Ischemic hepatitis is nearly always benign and
self-limited.
–The severity of the liver injury correlates with the
duration and extent of the hemodynamic
compromise.
–Prognosis is mostly related to the severity of the
Drugs induced hepatitis

Drugs induced hepatitis

•Drug hepatotoxicity is the most common cause
of fulminant liver failure in the United States

•Hepatotoxicity can occur with many drugs by a
variety of mechanisms.
Drugs induced hepatitis

SPECTRUM OF DRUG-INDUCED
HEPATOTOXICITY
–A variety of clinical presentations may be seen in
patients who develop drug hepatotoxicity, ranging
from
•asymptomatic mild biochemical abnormalities to an
acute illness with jaundice that resembles viral hepatitis
Drugs induced hepatitis
SPECTRUM OF DRUG-INDUCED HEPATOTOXICITY
- Subclinical
- Acute hepatic injury
- Cytotoxic
- Cholestatic
- mixed patterns
- Steatosis
- Chronic hepatic injury
- Chronic hepatitis
- steatosis
- fibrosis and cirrhosis
- Vascular disease
- granulomatous disease
- Neoplasia
Drugs induced hepatitis
Subclinical

–Many drugs can induce asymptomatic elevations
in liver enzymes without producing overt clinical
disease
•antibiotics, antidepressants, antihyperlipidemics,
sulfonamides, salicylates, sulfonylureas, and quinidine

–Most elevations are benign and resolve once the
offending agent has been discontinued.
Drugs induced hepatitis
•Acute hepatic injury

–Cytotoxic
•hepatocellular injury is similar to that seen in viral
hepatitis and includes necrosis, steatosis, and cellular
degeneration.
• acetaminophen, phenytoin, methyldopa, diclofenac

–Cholestatic
•resembles extrahepatic obstructive jaundice
•chlorpromazine, trimethoprim-sulfamethoxazole,
rifampin, erythromycin, amiodarone
Drugs induced hepatitis
•Acute hepatic injury

–Mixed patterns
•often seen in patients with hepatotoxicity due to phenytoin
•Such patients may be at increased risk to develop chronic liver
disease compared with other forms of hepatotoxicity

– Steatosis
• Drug-induced acute steatosis is uncommon and occurs less often
than chronic steatosis.
•acute steatosis tends to be microvesicular
•tetracycline, amiodarone, piroxicam
Drugs induced hepatitis
•Chronic hepatic injury

55. causes
•Hepatitis viruses
–Hepatitis A most common acute viral hepatitis but
rare for acute infection to progress to ALF
–Hepatitis B most common viral cause ALF
•Drug and toxins
–Acetaminophen, alcohol, Amiodarone, halothane,
isoniazid, methyldopa, NSAIDS, phenytoin,
rifampicin, sufonamides, tetracycline, tricyclic
antidepressants, valpoic acid
causes
•Vascular
–Portal vein thrombosis
–Budd-Chiari syndrome
–Veno-occlusive disease
–Ischemic hepatitis
•Metabolic
–Wilson’s disease
–Acute fatty liver of pregnancy
–Reye’s syndrome
causes
•Miscellaneous
–Malignant infiltration of the liver
–Heat stroke
–Sepsis
–Autoimmune hepatitis
Acetaminophen toxicity
Very high AST and ALT (often >3500 IU/L)
High INR
Low bilirubin
Ischemic hepatic injury
Very high AST and ALT (25–250 times of upper limit of normal)
Elevated serum LDH
Hepatitis B virus
Aminotransferase levels: 1000–2000 IU/L
ALT usually > AST
Wilson disease
Coombs-negative hemolytic anemia
Aminotransferase levels <2000 IU/L
AST/ALT ratio >2
Markedly low ALP (<40 IU/L)
ALP/total bilirubin ratio <4
Rapidly progressive renal failure
Low uric acid levels
Acute fatty liver of pregnancy/HELLP syndrome
Aminotransferase levels <1000 IU/L
Elevated bilirubin
Low platelet count
Herpes simplex virus
Markedly elevated aminotransferases
Leukopenia
Low bilirubin
Reye syndrome/Valproate or doxycycline toxicity Minor to moderate elevations in aminotransferase and bilirubin levels
Sign and symptom
•Acute liver failure
–Nonspecific symptoms
–Malaise
–Nausea
–Jaundice
–Ecchymoses
–Etc…
FHF complication
•Hepatic encephalopathy
•Cerebral edema
•Sepsis
•Renal failure
•Circulatory dysfunction
•Coagulopathy
•Gastrointestinal bleeding
•Pulmonary complication
•Metabolic disturbance, metabolic acidosis,
hypoglycemia, hypophosphatemia
FHF
Laboratory
•Hematology
–CBC, coagulation
•Biochemistry
–Blood glucose, BUN, creatinine, electrolyte, LFT
•Blood gas
•Virological markers
–Hepatitis profiles (A, B, C, delta)
•Microbiology
–Hemoculture
–Sputum/urine culture
Treatment
•Specific treatment
–Liver transplantation (stage 3 and 4)
•Complication treatment
–Hepatic encephalopathy
–Cerebral edema
–Sepsis
–Renal failure
–Circulatory dysfunction
–Coagulopathy
–Gastrointestinal bleeding
–Pulmonary complication
Complication treatment
•Hepatic encephalopathy
•↑ amonia WITHIN THE GUT LUMEN

•Concept
–Ammonia ↓
–Precipitating factors↓

•Restrict protein diet: 40 – 70 g/day
•Non-absorbable disaccharides: laculose
•Antibiotic: rifaximin, neomycin,
Complication treatment
•Cerebral edema
–Astrocyte edema
–Brainstem herniation, most causes of death
–Neurologic manifestations hypertonic, hyperflexia,
and altered pupillary responses

–Treatment:
•Elevated head position
•Manitol 0.5-1g/kg
ISCHEMIC HEPATITIS
(SHOCK LIVER, HYPOXIC
HEPATITIS)

ISCHEMIC HEPATITIS


•Ischemic hepatitis refers to diffuse hepatic
injury resulting from acute hypoperfusion



•Many cases of ischemic hepatitis occur in the
setting of congestive heart failure
ISCHEMIC HEPATITIS

•Clinical manifestations
–Any cause of shock or hemodynamic instability
can cause ischemic injury to the liver

–Ischemic injury can also be caused by focal
interruption of the hepatic blood supply

–The hemodynamic insult is usually apparent
clinically before evidence of liver injury appears
ISCHEMIC HEPATITIS

–Ischemic hepatitis is usually first detected because
of elevations in liver biochemical tests following a
hypotensive episode.

–Rare patients have symptoms suggesting acute
hepatitis, including nausea, vomiting, anorexia,
malaise, and right upper quadrant pain

–ischemia should always be considered in the
differential diagnosis of acute hepatitis, along with
more common causes such as viral infection,
ISCHEMIC HEPATITIS
•typical pattern of liver biochemical tests
consists of:

–rapid rise in serum aminotransferase levels
associated with an early massive rise in lactate
dehydrogenase (LDH) levels

–Peak aminotransferase levels are typically 25 to
250 times the upper limit of normal and are
reached within one to three days of the
hemodynamic insult

ISCHEMIC HEPATITIS
•Diagnosis

– There are relatively few causes of liver injury that
result in the striking increases in aminotransferase
levels

–Besides ischemic hepatitis, the most common are
acute viral hepatitis and acute drug- or toxin-
induced liver injury
ISCHEMIC HEPATITIS
•Pathology

–The histologic hallmark of ischemic hepatitis is
necrosis of hepatocytes
–associated with a variable degree of architectural
collapse around the central vein, depending upon
the duration and extent of ischemia

–There are characteristically few inflammatory cells
ISCHEMIC HEPATITIS
•Management
– aimed at restoring cardiac output and reversing
the underlying cause of hemodynamic instability.

•Prognosis:
– Ischemic hepatitis is nearly always benign and
self-limited.
–The severity of the liver injury correlates with the
duration and extent of the hemodynamic
compromise.
–Prognosis is mostly related to the severity of the
Drugs induced hepatitis

Drugs induced hepatitis

•Drug hepatotoxicity is the most common cause
of fulminant liver failure in the United States

•Hepatotoxicity can occur with many drugs by a
variety of mechanisms.
Drugs induced hepatitis

SPECTRUM OF DRUG-INDUCED
HEPATOTOXICITY
–A variety of clinical presentations may be seen in
patients who develop drug hepatotoxicity, ranging
from
•asymptomatic mild biochemical abnormalities to an
acute illness with jaundice that resembles viral hepatitis
Drugs induced hepatitis
SPECTRUM OF DRUG-INDUCED HEPATOTOXICITY
- Subclinical
- Acute hepatic injury
- Cytotoxic
- Cholestatic
- mixed patterns
- Steatosis
- Chronic hepatic injury
- Chronic hepatitis
- steatosis
- fibrosis and cirrhosis
- Vascular disease
- granulomatous disease
- Neoplasia
Drugs induced hepatitis
Subclinical

–Many drugs can induce asymptomatic elevations
in liver enzymes without producing overt clinical
disease
•antibiotics, antidepressants, antihyperlipidemics,
sulfonamides, salicylates, sulfonylureas, and quinidine

–Most elevations are benign and resolve once the
offending agent has been discontinued.
Drugs induced hepatitis
•Acute hepatic injury

–Cytotoxic
•hepatocellular injury is similar to that seen in viral
hepatitis and includes necrosis, steatosis, and cellular
degeneration.
• acetaminophen, phenytoin, methyldopa, diclofenac

–Cholestatic
•resembles extrahepatic obstructive jaundice
•chlorpromazine, trimethoprim-sulfamethoxazole,
rifampin, erythromycin, amiodarone
Drugs induced hepatitis
•Acute hepatic injury

–Mixed patterns
•often seen in patients with hepatotoxicity due to phenytoin
•Such patients may be at increased risk to develop chronic liver
disease compared with other forms of hepatotoxicity

– Steatosis
• Drug-induced acute steatosis is uncommon and occurs less often
than chronic steatosis.
•acute steatosis tends to be microvesicular
•tetracycline, amiodarone, piroxicam
Drugs induced hepatitis
•Chronic hepatic injury

56. causes
•Hepatitis viruses
–Hepatitis A most common acute viral hepatitis but
rare for acute infection to progress to ALF
–Hepatitis B most common viral cause ALF
•Drug and toxins
–Acetaminophen, alcohol, Amiodarone, halothane,
isoniazid, methyldopa, NSAIDS, phenytoin,
rifampicin, sufonamides, tetracycline, tricyclic
antidepressants, valpoic acid
causes
•Vascular
–Portal vein thrombosis
–Budd-Chiari syndrome
–Veno-occlusive disease
–Ischemic hepatitis
•Metabolic
–Wilson’s disease
–Acute fatty liver of pregnancy
–Reye’s syndrome
causes
•Miscellaneous
–Malignant infiltration of the liver
–Heat stroke
–Sepsis
–Autoimmune hepatitis
Acetaminophen toxicity
Very high AST and ALT (often >3500 IU/L)
High INR
Low bilirubin
Ischemic hepatic injury
Very high AST and ALT (25–250 times of upper limit of normal)
Elevated serum LDH
Hepatitis B virus
Aminotransferase levels: 1000–2000 IU/L
ALT usually > AST
Wilson disease
Coombs-negative hemolytic anemia
Aminotransferase levels <2000 IU/L
AST/ALT ratio >2
Markedly low ALP (<40 IU/L)
ALP/total bilirubin ratio <4
Rapidly progressive renal failure
Low uric acid levels
Acute fatty liver of pregnancy/HELLP syndrome
Aminotransferase levels <1000 IU/L
Elevated bilirubin
Low platelet count
Herpes simplex virus
Markedly elevated aminotransferases
Leukopenia
Low bilirubin
Reye syndrome/Valproate or doxycycline toxicity Minor to moderate elevations in aminotransferase and bilirubin levels
Sign and symptom
•Acute liver failure
–Nonspecific symptoms
–Malaise
–Nausea
–Jaundice
–Ecchymoses
–Etc…
FHF complication
•Hepatic encephalopathy
•Cerebral edema
•Sepsis
•Renal failure
•Circulatory dysfunction
•Coagulopathy
•Gastrointestinal bleeding
•Pulmonary complication
•Metabolic disturbance, metabolic acidosis,
hypoglycemia, hypophosphatemia
FHF
Laboratory
•Hematology
–CBC, coagulation
•Biochemistry
–Blood glucose, BUN, creatinine, electrolyte, LFT
•Blood gas
•Virological markers
–Hepatitis profiles (A, B, C, delta)
•Microbiology
–Hemoculture
–Sputum/urine culture
Treatment
•Specific treatment
–Liver transplantation (stage 3 and 4)
•Complication treatment
–Hepatic encephalopathy
–Cerebral edema
–Sepsis
–Renal failure
–Circulatory dysfunction
–Coagulopathy
–Gastrointestinal bleeding
–Pulmonary complication
Complication treatment
•Hepatic encephalopathy
•↑ amonia WITHIN THE GUT LUMEN

•Concept
–Ammonia ↓
–Precipitating factors↓

•Restrict protein diet: 40 – 70 g/day
•Non-absorbable disaccharides: laculose
•Antibiotic: rifaximin, neomycin,
Complication treatment
•Cerebral edema
–Astrocyte edema
–Brainstem herniation, most causes of death
–Neurologic manifestations hypertonic, hyperflexia,
and altered pupillary responses

–Treatment:
•Elevated head position
•Manitol 0.5-1g/kg
ISCHEMIC HEPATITIS
(SHOCK LIVER, HYPOXIC
HEPATITIS)

ISCHEMIC HEPATITIS


•Ischemic hepatitis refers to diffuse hepatic
injury resulting from acute hypoperfusion



•Many cases of ischemic hepatitis occur in the
setting of congestive heart failure
ISCHEMIC HEPATITIS

•Clinical manifestations
–Any cause of shock or hemodynamic instability
can cause ischemic injury to the liver

–Ischemic injury can also be caused by focal
interruption of the hepatic blood supply

–The hemodynamic insult is usually apparent
clinically before evidence of liver injury appears
ISCHEMIC HEPATITIS

–Ischemic hepatitis is usually first detected because
of elevations in liver biochemical tests following a
hypotensive episode.

–Rare patients have symptoms suggesting acute
hepatitis, including nausea, vomiting, anorexia,
malaise, and right upper quadrant pain

–ischemia should always be considered in the
differential diagnosis of acute hepatitis, along with
more common causes such as viral infection,
ISCHEMIC HEPATITIS
•typical pattern of liver biochemical tests
consists of:

–rapid rise in serum aminotransferase levels
associated with an early massive rise in lactate
dehydrogenase (LDH) levels

–Peak aminotransferase levels are typically 25 to
250 times the upper limit of normal and are
reached within one to three days of the
hemodynamic insult

ISCHEMIC HEPATITIS
•Diagnosis

– There are relatively few causes of liver injury that
result in the striking increases in aminotransferase
levels

–Besides ischemic hepatitis, the most common are
acute viral hepatitis and acute drug- or toxin-
induced liver injury
ISCHEMIC HEPATITIS
•Pathology

–The histologic hallmark of ischemic hepatitis is
necrosis of hepatocytes
–associated with a variable degree of architectural
collapse around the central vein, depending upon
the duration and extent of ischemia

–There are characteristically few inflammatory cells
ISCHEMIC HEPATITIS
•Management
– aimed at restoring cardiac output and reversing
the underlying cause of hemodynamic instability.

•Prognosis:
– Ischemic hepatitis is nearly always benign and
self-limited.
–The severity of the liver injury correlates with the
duration and extent of the hemodynamic
compromise.
–Prognosis is mostly related to the severity of the
Drugs induced hepatitis

Drugs induced hepatitis

•Drug hepatotoxicity is the most common cause
of fulminant liver failure in the United States

•Hepatotoxicity can occur with many drugs by a
variety of mechanisms.
Drugs induced hepatitis

SPECTRUM OF DRUG-INDUCED
HEPATOTOXICITY
–A variety of clinical presentations may be seen in
patients who develop drug hepatotoxicity, ranging
from
•asymptomatic mild biochemical abnormalities to an
acute illness with jaundice that resembles viral hepatitis
Drugs induced hepatitis
SPECTRUM OF DRUG-INDUCED HEPATOTOXICITY
- Subclinical
- Acute hepatic injury
- Cytotoxic
- Cholestatic
- mixed patterns
- Steatosis
- Chronic hepatic injury
- Chronic hepatitis
- steatosis
- fibrosis and cirrhosis
- Vascular disease
- granulomatous disease
- Neoplasia
Drugs induced hepatitis
Subclinical

–Many drugs can induce asymptomatic elevations
in liver enzymes without producing overt clinical
disease
•antibiotics, antidepressants, antihyperlipidemics,
sulfonamides, salicylates, sulfonylureas, and quinidine

–Most elevations are benign and resolve once the
offending agent has been discontinued.
Drugs induced hepatitis
•Acute hepatic injury

–Cytotoxic
•hepatocellular injury is similar to that seen in viral
hepatitis and includes necrosis, steatosis, and cellular
degeneration.
• acetaminophen, phenytoin, methyldopa, diclofenac

–Cholestatic
•resembles extrahepatic obstructive jaundice
•chlorpromazine, trimethoprim-sulfamethoxazole,
rifampin, erythromycin, amiodarone
Drugs induced hepatitis
•Acute hepatic injury

–Mixed patterns
•often seen in patients with hepatotoxicity due to phenytoin
•Such patients may be at increased risk to develop chronic liver
disease compared with other forms of hepatotoxicity

– Steatosis
• Drug-induced acute steatosis is uncommon and occurs less often
than chronic steatosis.
•acute steatosis tends to be microvesicular
•tetracycline, amiodarone, piroxicam
Drugs induced hepatitis
•Chronic hepatic injury

57. causes
•Hepatitis viruses
–Hepatitis A most common acute viral hepatitis but
rare for acute infection to progress to ALF
–Hepatitis B most common viral cause ALF
•Drug and toxins
–Acetaminophen, alcohol, Amiodarone, halothane,
isoniazid, methyldopa, NSAIDS, phenytoin,
rifampicin, sufonamides, tetracycline, tricyclic
antidepressants, valpoic acid
causes
•Vascular
–Portal vein thrombosis
–Budd-Chiari syndrome
–Veno-occlusive disease
–Ischemic hepatitis
•Metabolic
–Wilson’s disease
–Acute fatty liver of pregnancy
–Reye’s syndrome
causes
•Miscellaneous
–Malignant infiltration of the liver
–Heat stroke
–Sepsis
–Autoimmune hepatitis
Acetaminophen toxicity
Very high AST and ALT (often >3500 IU/L)
High INR
Low bilirubin
Ischemic hepatic injury
Very high AST and ALT (25–250 times of upper limit of normal)
Elevated serum LDH
Hepatitis B virus
Aminotransferase levels: 1000–2000 IU/L
ALT usually > AST
Wilson disease
Coombs-negative hemolytic anemia
Aminotransferase levels <2000 IU/L
AST/ALT ratio >2
Markedly low ALP (<40 IU/L)
ALP/total bilirubin ratio <4
Rapidly progressive renal failure
Low uric acid levels
Acute fatty liver of pregnancy/HELLP syndrome
Aminotransferase levels <1000 IU/L
Elevated bilirubin
Low platelet count
Herpes simplex virus
Markedly elevated aminotransferases
Leukopenia
Low bilirubin
Reye syndrome/Valproate or doxycycline toxicity Minor to moderate elevations in aminotransferase and bilirubin levels
Sign and symptom
•Acute liver failure
–Nonspecific symptoms
–Malaise
–Nausea
–Jaundice
–Ecchymoses
–Etc…
FHF complication
•Hepatic encephalopathy
•Cerebral edema
•Sepsis
•Renal failure
•Circulatory dysfunction
•Coagulopathy
•Gastrointestinal bleeding
•Pulmonary complication
•Metabolic disturbance, metabolic acidosis,
hypoglycemia, hypophosphatemia
FHF
Laboratory
•Hematology
–CBC, coagulation
•Biochemistry
–Blood glucose, BUN, creatinine, electrolyte, LFT
•Blood gas
•Virological markers
–Hepatitis profiles (A, B, C, delta)
•Microbiology
–Hemoculture
–Sputum/urine culture
Treatment
•Specific treatment
–Liver transplantation (stage 3 and 4)
•Complication treatment
–Hepatic encephalopathy
–Cerebral edema
–Sepsis
–Renal failure
–Circulatory dysfunction
–Coagulopathy
–Gastrointestinal bleeding
–Pulmonary complication
Complication treatment
•Hepatic encephalopathy
•↑ amonia WITHIN THE GUT LUMEN

•Concept
–Ammonia ↓
–Precipitating factors↓

•Restrict protein diet: 40 – 70 g/day
•Non-absorbable disaccharides: laculose
•Antibiotic: rifaximin, neomycin,
Complication treatment
•Cerebral edema
–Astrocyte edema
–Brainstem herniation, most causes of death
–Neurologic manifestations hypertonic, hyperflexia,
and altered pupillary responses

–Treatment:
•Elevated head position
•Manitol 0.5-1g/kg
ISCHEMIC HEPATITIS
(SHOCK LIVER, HYPOXIC
HEPATITIS)

ISCHEMIC HEPATITIS


•Ischemic hepatitis refers to diffuse hepatic
injury resulting from acute hypoperfusion



•Many cases of ischemic hepatitis occur in the
setting of congestive heart failure
ISCHEMIC HEPATITIS

•Clinical manifestations
–Any cause of shock or hemodynamic instability
can cause ischemic injury to the liver

–Ischemic injury can also be caused by focal
interruption of the hepatic blood supply

–The hemodynamic insult is usually apparent
clinically before evidence of liver injury appears
ISCHEMIC HEPATITIS

–Ischemic hepatitis is usually first detected because
of elevations in liver biochemical tests following a
hypotensive episode.

–Rare patients have symptoms suggesting acute
hepatitis, including nausea, vomiting, anorexia,
malaise, and right upper quadrant pain

–ischemia should always be considered in the
differential diagnosis of acute hepatitis, along with
more common causes such as viral infection,
ISCHEMIC HEPATITIS
•typical pattern of liver biochemical tests
consists of:

–rapid rise in serum aminotransferase levels
associated with an early massive rise in lactate
dehydrogenase (LDH) levels

–Peak aminotransferase levels are typically 25 to
250 times the upper limit of normal and are
reached within one to three days of the
hemodynamic insult

ISCHEMIC HEPATITIS
•Diagnosis

– There are relatively few causes of liver injury that
result in the striking increases in aminotransferase
levels

–Besides ischemic hepatitis, the most common are
acute viral hepatitis and acute drug- or toxin-
induced liver injury
ISCHEMIC HEPATITIS
•Pathology

–The histologic hallmark of ischemic hepatitis is
necrosis of hepatocytes
–associated with a variable degree of architectural
collapse around the central vein, depending upon
the duration and extent of ischemia

–There are characteristically few inflammatory cells
ISCHEMIC HEPATITIS
•Management
– aimed at restoring cardiac output and reversing
the underlying cause of hemodynamic instability.

•Prognosis:
– Ischemic hepatitis is nearly always benign and
self-limited.
–The severity of the liver injury correlates with the
duration and extent of the hemodynamic
compromise.
–Prognosis is mostly related to the severity of the
Drugs induced hepatitis

Drugs induced hepatitis

•Drug hepatotoxicity is the most common cause
of fulminant liver failure in the United States

•Hepatotoxicity can occur with many drugs by a
variety of mechanisms.
Drugs induced hepatitis

SPECTRUM OF DRUG-INDUCED
HEPATOTOXICITY
–A variety of clinical presentations may be seen in
patients who develop drug hepatotoxicity, ranging
from
•asymptomatic mild biochemical abnormalities to an
acute illness with jaundice that resembles viral hepatitis
Drugs induced hepatitis
SPECTRUM OF DRUG-INDUCED HEPATOTOXICITY
- Subclinical
- Acute hepatic injury
- Cytotoxic
- Cholestatic
- mixed patterns
- Steatosis
- Chronic hepatic injury
- Chronic hepatitis
- steatosis
- fibrosis and cirrhosis
- Vascular disease
- granulomatous disease
- Neoplasia
Drugs induced hepatitis
Subclinical

–Many drugs can induce asymptomatic elevations
in liver enzymes without producing overt clinical
disease
•antibiotics, antidepressants, antihyperlipidemics,
sulfonamides, salicylates, sulfonylureas, and quinidine

–Most elevations are benign and resolve once the
offending agent has been discontinued.
Drugs induced hepatitis
•Acute hepatic injury

–Cytotoxic
•hepatocellular injury is similar to that seen in viral
hepatitis and includes necrosis, steatosis, and cellular
degeneration.
• acetaminophen, phenytoin, methyldopa, diclofenac

–Cholestatic
•resembles extrahepatic obstructive jaundice
•chlorpromazine, trimethoprim-sulfamethoxazole,
rifampin, erythromycin, amiodarone
Drugs induced hepatitis
•Acute hepatic injury

–Mixed patterns
•often seen in patients with hepatotoxicity due to phenytoin
•Such patients may be at increased risk to develop chronic liver
disease compared with other forms of hepatotoxicity

– Steatosis
• Drug-induced acute steatosis is uncommon and occurs less often
than chronic steatosis.
•acute steatosis tends to be microvesicular
•tetracycline, amiodarone, piroxicam
Drugs induced hepatitis
•Chronic hepatic injury

58. causes
•Hepatitis viruses
–Hepatitis A most common acute viral hepatitis but
rare for acute infection to progress to ALF
–Hepatitis B most common viral cause ALF
•Drug and toxins
–Acetaminophen, alcohol, Amiodarone, halothane,
isoniazid, methyldopa, NSAIDS, phenytoin,
rifampicin, sufonamides, tetracycline, tricyclic
antidepressants, valpoic acid
causes
•Vascular
–Portal vein thrombosis
–Budd-Chiari syndrome
–Veno-occlusive disease
–Ischemic hepatitis
•Metabolic
–Wilson’s disease
–Acute fatty liver of pregnancy
–Reye’s syndrome
causes
•Miscellaneous
–Malignant infiltration of the liver
–Heat stroke
–Sepsis
–Autoimmune hepatitis
Acetaminophen toxicity
Very high AST and ALT (often >3500 IU/L)
High INR
Low bilirubin
Ischemic hepatic injury
Very high AST and ALT (25–250 times of upper limit of normal)
Elevated serum LDH
Hepatitis B virus
Aminotransferase levels: 1000–2000 IU/L
ALT usually > AST
Wilson disease
Coombs-negative hemolytic anemia
Aminotransferase levels <2000 IU/L
AST/ALT ratio >2
Markedly low ALP (<40 IU/L)
ALP/total bilirubin ratio <4
Rapidly progressive renal failure
Low uric acid levels
Acute fatty liver of pregnancy/HELLP syndrome
Aminotransferase levels <1000 IU/L
Elevated bilirubin
Low platelet count
Herpes simplex virus
Markedly elevated aminotransferases
Leukopenia
Low bilirubin
Reye syndrome/Valproate or doxycycline toxicity Minor to moderate elevations in aminotransferase and bilirubin levels
Sign and symptom
•Acute liver failure
–Nonspecific symptoms
–Malaise
–Nausea
–Jaundice
–Ecchymoses
–Etc…
FHF complication
•Hepatic encephalopathy
•Cerebral edema
•Sepsis
•Renal failure
•Circulatory dysfunction
•Coagulopathy
•Gastrointestinal bleeding
•Pulmonary complication
•Metabolic disturbance, metabolic acidosis,
hypoglycemia, hypophosphatemia
FHF
Laboratory
•Hematology
–CBC, coagulation
•Biochemistry
–Blood glucose, BUN, creatinine, electrolyte, LFT
•Blood gas
•Virological markers
–Hepatitis profiles (A, B, C, delta)
•Microbiology
–Hemoculture
–Sputum/urine culture
Treatment
•Specific treatment
–Liver transplantation (stage 3 and 4)
•Complication treatment
–Hepatic encephalopathy
–Cerebral edema
–Sepsis
–Renal failure
–Circulatory dysfunction
–Coagulopathy
–Gastrointestinal bleeding
–Pulmonary complication
Complication treatment
•Hepatic encephalopathy
•↑ amonia WITHIN THE GUT LUMEN

•Concept
–Ammonia ↓
–Precipitating factors↓

•Restrict protein diet: 40 – 70 g/day
•Non-absorbable disaccharides: laculose
•Antibiotic: rifaximin, neomycin,
Complication treatment
•Cerebral edema
–Astrocyte edema
–Brainstem herniation, most causes of death
–Neurologic manifestations hypertonic, hyperflexia,
and altered pupillary responses

–Treatment:
•Elevated head position
•Manitol 0.5-1g/kg
ISCHEMIC HEPATITIS
(SHOCK LIVER, HYPOXIC
HEPATITIS)

ISCHEMIC HEPATITIS


•Ischemic hepatitis refers to diffuse hepatic
injury resulting from acute hypoperfusion



•Many cases of ischemic hepatitis occur in the
setting of congestive heart failure
ISCHEMIC HEPATITIS

•Clinical manifestations
–Any cause of shock or hemodynamic instability
can cause ischemic injury to the liver

–Ischemic injury can also be caused by focal
interruption of the hepatic blood supply

–The hemodynamic insult is usually apparent
clinically before evidence of liver injury appears
ISCHEMIC HEPATITIS

–Ischemic hepatitis is usually first detected because
of elevations in liver biochemical tests following a
hypotensive episode.

–Rare patients have symptoms suggesting acute
hepatitis, including nausea, vomiting, anorexia,
malaise, and right upper quadrant pain

–ischemia should always be considered in the
differential diagnosis of acute hepatitis, along with
more common causes such as viral infection,
ISCHEMIC HEPATITIS
•typical pattern of liver biochemical tests
consists of:

–rapid rise in serum aminotransferase levels
associated with an early massive rise in lactate
dehydrogenase (LDH) levels

–Peak aminotransferase levels are typically 25 to
250 times the upper limit of normal and are
reached within one to three days of the
hemodynamic insult

ISCHEMIC HEPATITIS
•Diagnosis

– There are relatively few causes of liver injury that
result in the striking increases in aminotransferase
levels

–Besides ischemic hepatitis, the most common are
acute viral hepatitis and acute drug- or toxin-
induced liver injury
ISCHEMIC HEPATITIS
•Pathology

–The histologic hallmark of ischemic hepatitis is
necrosis of hepatocytes
–associated with a variable degree of architectural
collapse around the central vein, depending upon
the duration and extent of ischemia

–There are characteristically few inflammatory cells
ISCHEMIC HEPATITIS
•Management
– aimed at restoring cardiac output and reversing
the underlying cause of hemodynamic instability.

•Prognosis:
– Ischemic hepatitis is nearly always benign and
self-limited.
–The severity of the liver injury correlates with the
duration and extent of the hemodynamic
compromise.
–Prognosis is mostly related to the severity of the
Drugs induced hepatitis

Drugs induced hepatitis

•Drug hepatotoxicity is the most common cause
of fulminant liver failure in the United States

•Hepatotoxicity can occur with many drugs by a
variety of mechanisms.
Drugs induced hepatitis

SPECTRUM OF DRUG-INDUCED
HEPATOTOXICITY
–A variety of clinical presentations may be seen in
patients who develop drug hepatotoxicity, ranging
from
•asymptomatic mild biochemical abnormalities to an
acute illness with jaundice that resembles viral hepatitis
Drugs induced hepatitis
SPECTRUM OF DRUG-INDUCED HEPATOTOXICITY
- Subclinical
- Acute hepatic injury
- Cytotoxic
- Cholestatic
- mixed patterns
- Steatosis
- Chronic hepatic injury
- Chronic hepatitis
- steatosis
- fibrosis and cirrhosis
- Vascular disease
- granulomatous disease
- Neoplasia
Drugs induced hepatitis
Subclinical

–Many drugs can induce asymptomatic elevations
in liver enzymes without producing overt clinical
disease
•antibiotics, antidepressants, antihyperlipidemics,
sulfonamides, salicylates, sulfonylureas, and quinidine

–Most elevations are benign and resolve once the
offending agent has been discontinued.
Drugs induced hepatitis
•Acute hepatic injury

–Cytotoxic
•hepatocellular injury is similar to that seen in viral
hepatitis and includes necrosis, steatosis, and cellular
degeneration.
• acetaminophen, phenytoin, methyldopa, diclofenac

–Cholestatic
•resembles extrahepatic obstructive jaundice
•chlorpromazine, trimethoprim-sulfamethoxazole,
rifampin, erythromycin, amiodarone
Drugs induced hepatitis
•Acute hepatic injury

–Mixed patterns
•often seen in patients with hepatotoxicity due to phenytoin
•Such patients may be at increased risk to develop chronic liver
disease compared with other forms of hepatotoxicity

– Steatosis
• Drug-induced acute steatosis is uncommon and occurs less often
than chronic steatosis.
•acute steatosis tends to be microvesicular
•tetracycline, amiodarone, piroxicam
Drugs induced hepatitis
•Chronic hepatic injury

59. causes
•Hepatitis viruses
–Hepatitis A most common acute viral hepatitis but
rare for acute infection to progress to ALF
–Hepatitis B most common viral cause ALF
•Drug and toxins
–Acetaminophen, alcohol, Amiodarone, halothane,
isoniazid, methyldopa, NSAIDS, phenytoin,
rifampicin, sufonamides, tetracycline, tricyclic
antidepressants, valpoic acid
causes
•Vascular
–Portal vein thrombosis
–Budd-Chiari syndrome
–Veno-occlusive disease
–Ischemic hepatitis
•Metabolic
–Wilson’s disease
–Acute fatty liver of pregnancy
–Reye’s syndrome
causes
•Miscellaneous
–Malignant infiltration of the liver
–Heat stroke
–Sepsis
–Autoimmune hepatitis
Acetaminophen toxicity
Very high AST and ALT (often >3500 IU/L)
High INR
Low bilirubin
Ischemic hepatic injury
Very high AST and ALT (25–250 times of upper limit of normal)
Elevated serum LDH
Hepatitis B virus
Aminotransferase levels: 1000–2000 IU/L
ALT usually > AST
Wilson disease
Coombs-negative hemolytic anemia
Aminotransferase levels <2000 IU/L
AST/ALT ratio >2
Markedly low ALP (<40 IU/L)
ALP/total bilirubin ratio <4
Rapidly progressive renal failure
Low uric acid levels
Acute fatty liver of pregnancy/HELLP syndrome
Aminotransferase levels <1000 IU/L
Elevated bilirubin
Low platelet count
Herpes simplex virus
Markedly elevated aminotransferases
Leukopenia
Low bilirubin
Reye syndrome/Valproate or doxycycline toxicity Minor to moderate elevations in aminotransferase and bilirubin levels
Sign and symptom
•Acute liver failure
–Nonspecific symptoms
–Malaise
–Nausea
–Jaundice
–Ecchymoses
–Etc…
FHF complication
•Hepatic encephalopathy
•Cerebral edema
•Sepsis
•Renal failure
•Circulatory dysfunction
•Coagulopathy
•Gastrointestinal bleeding
•Pulmonary complication
•Metabolic disturbance, metabolic acidosis,
hypoglycemia, hypophosphatemia
FHF
Laboratory
•Hematology
–CBC, coagulation
•Biochemistry
–Blood glucose, BUN, creatinine, electrolyte, LFT
•Blood gas
•Virological markers
–Hepatitis profiles (A, B, C, delta)
•Microbiology
–Hemoculture
–Sputum/urine culture
Treatment
•Specific treatment
–Liver transplantation (stage 3 and 4)
•Complication treatment
–Hepatic encephalopathy
–Cerebral edema
–Sepsis
–Renal failure
–Circulatory dysfunction
–Coagulopathy
–Gastrointestinal bleeding
–Pulmonary complication
Complication treatment
•Hepatic encephalopathy
•↑ amonia WITHIN THE GUT LUMEN

•Concept
–Ammonia ↓
–Precipitating factors↓

•Restrict protein diet: 40 – 70 g/day
•Non-absorbable disaccharides: laculose
•Antibiotic: rifaximin, neomycin,
Complication treatment
•Cerebral edema
–Astrocyte edema
–Brainstem herniation, most causes of death
–Neurologic manifestations hypertonic, hyperflexia,
and altered pupillary responses

–Treatment:
•Elevated head position
•Manitol 0.5-1g/kg
ISCHEMIC HEPATITIS
(SHOCK LIVER, HYPOXIC
HEPATITIS)

ISCHEMIC HEPATITIS


•Ischemic hepatitis refers to diffuse hepatic
injury resulting from acute hypoperfusion



•Many cases of ischemic hepatitis occur in the
setting of congestive heart failure
ISCHEMIC HEPATITIS

•Clinical manifestations
–Any cause of shock or hemodynamic instability
can cause ischemic injury to the liver

–Ischemic injury can also be caused by focal
interruption of the hepatic blood supply

–The hemodynamic insult is usually apparent
clinically before evidence of liver injury appears
ISCHEMIC HEPATITIS

–Ischemic hepatitis is usually first detected because
of elevations in liver biochemical tests following a
hypotensive episode.

–Rare patients have symptoms suggesting acute
hepatitis, including nausea, vomiting, anorexia,
malaise, and right upper quadrant pain

–ischemia should always be considered in the
differential diagnosis of acute hepatitis, along with
more common causes such as viral infection,
ISCHEMIC HEPATITIS
•typical pattern of liver biochemical tests
consists of:

–rapid rise in serum aminotransferase levels
associated with an early massive rise in lactate
dehydrogenase (LDH) levels

–Peak aminotransferase levels are typically 25 to
250 times the upper limit of normal and are
reached within one to three days of the
hemodynamic insult

ISCHEMIC HEPATITIS
•Diagnosis

– There are relatively few causes of liver injury that
result in the striking increases in aminotransferase
levels

–Besides ischemic hepatitis, the most common are
acute viral hepatitis and acute drug- or toxin-
induced liver injury
ISCHEMIC HEPATITIS
•Pathology

–The histologic hallmark of ischemic hepatitis is
necrosis of hepatocytes
–associated with a variable degree of architectural
collapse around the central vein, depending upon
the duration and extent of ischemia

–There are characteristically few inflammatory cells
ISCHEMIC HEPATITIS
•Management
– aimed at restoring cardiac output and reversing
the underlying cause of hemodynamic instability.

•Prognosis:
– Ischemic hepatitis is nearly always benign and
self-limited.
–The severity of the liver injury correlates with the
duration and extent of the hemodynamic
compromise.
–Prognosis is mostly related to the severity of the
Drugs induced hepatitis

Drugs induced hepatitis

•Drug hepatotoxicity is the most common cause
of fulminant liver failure in the United States

•Hepatotoxicity can occur with many drugs by a
variety of mechanisms.
Drugs induced hepatitis

SPECTRUM OF DRUG-INDUCED
HEPATOTOXICITY
–A variety of clinical presentations may be seen in
patients who develop drug hepatotoxicity, ranging
from
•asymptomatic mild biochemical abnormalities to an
acute illness with jaundice that resembles viral hepatitis
Drugs induced hepatitis
SPECTRUM OF DRUG-INDUCED HEPATOTOXICITY
- Subclinical
- Acute hepatic injury
- Cytotoxic
- Cholestatic
- mixed patterns
- Steatosis
- Chronic hepatic injury
- Chronic hepatitis
- steatosis
- fibrosis and cirrhosis
- Vascular disease
- granulomatous disease
- Neoplasia
Drugs induced hepatitis
Subclinical

–Many drugs can induce asymptomatic elevations
in liver enzymes without producing overt clinical
disease
•antibiotics, antidepressants, antihyperlipidemics,
sulfonamides, salicylates, sulfonylureas, and quinidine

–Most elevations are benign and resolve once the
offending agent has been discontinued.
Drugs induced hepatitis
•Acute hepatic injury

–Cytotoxic
•hepatocellular injury is similar to that seen in viral
hepatitis and includes necrosis, steatosis, and cellular
degeneration.
• acetaminophen, phenytoin, methyldopa, diclofenac

–Cholestatic
•resembles extrahepatic obstructive jaundice
•chlorpromazine, trimethoprim-sulfamethoxazole,
rifampin, erythromycin, amiodarone
Drugs induced hepatitis
•Acute hepatic injury

–Mixed patterns
•often seen in patients with hepatotoxicity due to phenytoin
•Such patients may be at increased risk to develop chronic liver
disease compared with other forms of hepatotoxicity

– Steatosis
• Drug-induced acute steatosis is uncommon and occurs less often
than chronic steatosis.
•acute steatosis tends to be microvesicular
•tetracycline, amiodarone, piroxicam
Drugs induced hepatitis
•Chronic hepatic injury

60. causes
•Hepatitis viruses
–Hepatitis A most common acute viral hepatitis but
rare for acute infection to progress to ALF
–Hepatitis B most common viral cause ALF
•Drug and toxins
–Acetaminophen, alcohol, Amiodarone, halothane,
isoniazid, methyldopa, NSAIDS, phenytoin,
rifampicin, sufonamides, tetracycline, tricyclic
antidepressants, valpoic acid
causes
•Vascular
–Portal vein thrombosis
–Budd-Chiari syndrome
–Veno-occlusive disease
–Ischemic hepatitis
•Metabolic
–Wilson’s disease
–Acute fatty liver of pregnancy
–Reye’s syndrome
causes
•Miscellaneous
–Malignant infiltration of the liver
–Heat stroke
–Sepsis
–Autoimmune hepatitis
Acetaminophen toxicity
Very high AST and ALT (often >3500 IU/L)
High INR
Low bilirubin
Ischemic hepatic injury
Very high AST and ALT (25–250 times of upper limit of normal)
Elevated serum LDH
Hepatitis B virus
Aminotransferase levels: 1000–2000 IU/L
ALT usually > AST
Wilson disease
Coombs-negative hemolytic anemia
Aminotransferase levels <2000 IU/L
AST/ALT ratio >2
Markedly low ALP (<40 IU/L)
ALP/total bilirubin ratio <4
Rapidly progressive renal failure
Low uric acid levels
Acute fatty liver of pregnancy/HELLP syndrome
Aminotransferase levels <1000 IU/L
Elevated bilirubin
Low platelet count
Herpes simplex virus
Markedly elevated aminotransferases
Leukopenia
Low bilirubin
Reye syndrome/Valproate or doxycycline toxicity Minor to moderate elevations in aminotransferase and bilirubin levels
Sign and symptom
•Acute liver failure
–Nonspecific symptoms
–Malaise
–Nausea
–Jaundice
–Ecchymoses
–Etc…
FHF complication
•Hepatic encephalopathy
•Cerebral edema
•Sepsis
•Renal failure
•Circulatory dysfunction
•Coagulopathy
•Gastrointestinal bleeding
•Pulmonary complication
•Metabolic disturbance, metabolic acidosis,
hypoglycemia, hypophosphatemia
FHF
Laboratory
•Hematology
–CBC, coagulation
•Biochemistry
–Blood glucose, BUN, creatinine, electrolyte, LFT
•Blood gas
•Virological markers
–Hepatitis profiles (A, B, C, delta)
•Microbiology
–Hemoculture
–Sputum/urine culture
Treatment
•Specific treatment
–Liver transplantation (stage 3 and 4)
•Complication treatment
–Hepatic encephalopathy
–Cerebral edema
–Sepsis
–Renal failure
–Circulatory dysfunction
–Coagulopathy
–Gastrointestinal bleeding
–Pulmonary complication
Complication treatment
•Hepatic encephalopathy
•↑ amonia WITHIN THE GUT LUMEN

•Concept
–Ammonia ↓
–Precipitating factors↓

•Restrict protein diet: 40 – 70 g/day
•Non-absorbable disaccharides: laculose
•Antibiotic: rifaximin, neomycin,
Complication treatment
•Cerebral edema
–Astrocyte edema
–Brainstem herniation, most causes of death
–Neurologic manifestations hypertonic, hyperflexia,
and altered pupillary responses

–Treatment:
•Elevated head position
•Manitol 0.5-1g/kg
ISCHEMIC HEPATITIS
(SHOCK LIVER, HYPOXIC
HEPATITIS)

ISCHEMIC HEPATITIS


•Ischemic hepatitis refers to diffuse hepatic
injury resulting from acute hypoperfusion



•Many cases of ischemic hepatitis occur in the
setting of congestive heart failure
ISCHEMIC HEPATITIS

•Clinical manifestations
–Any cause of shock or hemodynamic instability
can cause ischemic injury to the liver

–Ischemic injury can also be caused by focal
interruption of the hepatic blood supply

–The hemodynamic insult is usually apparent
clinically before evidence of liver injury appears
ISCHEMIC HEPATITIS

–Ischemic hepatitis is usually first detected because
of elevations in liver biochemical tests following a
hypotensive episode.

–Rare patients have symptoms suggesting acute
hepatitis, including nausea, vomiting, anorexia,
malaise, and right upper quadrant pain

–ischemia should always be considered in the
differential diagnosis of acute hepatitis, along with
more common causes such as viral infection,
ISCHEMIC HEPATITIS
•typical pattern of liver biochemical tests
consists of:

–rapid rise in serum aminotransferase levels
associated with an early massive rise in lactate
dehydrogenase (LDH) levels

–Peak aminotransferase levels are typically 25 to
250 times the upper limit of normal and are
reached within one to three days of the
hemodynamic insult

ISCHEMIC HEPATITIS
•Diagnosis

– There are relatively few causes of liver injury that
result in the striking increases in aminotransferase
levels

–Besides ischemic hepatitis, the most common are
acute viral hepatitis and acute drug- or toxin-
induced liver injury
ISCHEMIC HEPATITIS
•Pathology

–The histologic hallmark of ischemic hepatitis is
necrosis of hepatocytes
–associated with a variable degree of architectural
collapse around the central vein, depending upon
the duration and extent of ischemia

–There are characteristically few inflammatory cells
ISCHEMIC HEPATITIS
•Management
– aimed at restoring cardiac output and reversing
the underlying cause of hemodynamic instability.

•Prognosis:
– Ischemic hepatitis is nearly always benign and
self-limited.
–The severity of the liver injury correlates with the
duration and extent of the hemodynamic
compromise.
–Prognosis is mostly related to the severity of the
Drugs induced hepatitis

Drugs induced hepatitis

•Drug hepatotoxicity is the most common cause
of fulminant liver failure in the United States

•Hepatotoxicity can occur with many drugs by a
variety of mechanisms.
Drugs induced hepatitis

SPECTRUM OF DRUG-INDUCED
HEPATOTOXICITY
–A variety of clinical presentations may be seen in
patients who develop drug hepatotoxicity, ranging
from
•asymptomatic mild biochemical abnormalities to an
acute illness with jaundice that resembles viral hepatitis
Drugs induced hepatitis
SPECTRUM OF DRUG-INDUCED HEPATOTOXICITY
- Subclinical
- Acute hepatic injury
- Cytotoxic
- Cholestatic
- mixed patterns
- Steatosis
- Chronic hepatic injury
- Chronic hepatitis
- steatosis
- fibrosis and cirrhosis
- Vascular disease
- granulomatous disease
- Neoplasia
Drugs induced hepatitis
Subclinical

–Many drugs can induce asymptomatic elevations
in liver enzymes without producing overt clinical
disease
•antibiotics, antidepressants, antihyperlipidemics,
sulfonamides, salicylates, sulfonylureas, and quinidine

–Most elevations are benign and resolve once the
offending agent has been discontinued.
Drugs induced hepatitis
•Acute hepatic injury

–Cytotoxic
•hepatocellular injury is similar to that seen in viral
hepatitis and includes necrosis, steatosis, and cellular
degeneration.
• acetaminophen, phenytoin, methyldopa, diclofenac

–Cholestatic
•resembles extrahepatic obstructive jaundice
•chlorpromazine, trimethoprim-sulfamethoxazole,
rifampin, erythromycin, amiodarone
Drugs induced hepatitis
•Acute hepatic injury

–Mixed patterns
•often seen in patients with hepatotoxicity due to phenytoin
•Such patients may be at increased risk to develop chronic liver
disease compared with other forms of hepatotoxicity

– Steatosis
• Drug-induced acute steatosis is uncommon and occurs less often
than chronic steatosis.
•acute steatosis tends to be microvesicular
•tetracycline, amiodarone, piroxicam
Drugs induced hepatitis
•Chronic hepatic injury

61. causes
•Hepatitis viruses
–Hepatitis A most common acute viral hepatitis but
rare for acute infection to progress to ALF
–Hepatitis B most common viral cause ALF
•Drug and toxins
–Acetaminophen, alcohol, Amiodarone, halothane,
isoniazid, methyldopa, NSAIDS, phenytoin,
rifampicin, sufonamides, tetracycline, tricyclic
antidepressants, valpoic acid
causes
•Vascular
–Portal vein thrombosis
–Budd-Chiari syndrome
–Veno-occlusive disease
–Ischemic hepatitis
•Metabolic
–Wilson’s disease
–Acute fatty liver of pregnancy
–Reye’s syndrome
causes
•Miscellaneous
–Malignant infiltration of the liver
–Heat stroke
–Sepsis
–Autoimmune hepatitis
Acetaminophen toxicity
Very high AST and ALT (often >3500 IU/L)
High INR
Low bilirubin
Ischemic hepatic injury
Very high AST and ALT (25–250 times of upper limit of normal)
Elevated serum LDH
Hepatitis B virus
Aminotransferase levels: 1000–2000 IU/L
ALT usually > AST
Wilson disease
Coombs-negative hemolytic anemia
Aminotransferase levels <2000 IU/L
AST/ALT ratio >2
Markedly low ALP (<40 IU/L)
ALP/total bilirubin ratio <4
Rapidly progressive renal failure
Low uric acid levels
Acute fatty liver of pregnancy/HELLP syndrome
Aminotransferase levels <1000 IU/L
Elevated bilirubin
Low platelet count
Herpes simplex virus
Markedly elevated aminotransferases
Leukopenia
Low bilirubin
Reye syndrome/Valproate or doxycycline toxicity Minor to moderate elevations in aminotransferase and bilirubin levels
Sign and symptom
•Acute liver failure
–Nonspecific symptoms
–Malaise
–Nausea
–Jaundice
–Ecchymoses
–Etc…
FHF complication
•Hepatic encephalopathy
•Cerebral edema
•Sepsis
•Renal failure
•Circulatory dysfunction
•Coagulopathy
•Gastrointestinal bleeding
•Pulmonary complication
•Metabolic disturbance, metabolic acidosis,
hypoglycemia, hypophosphatemia
FHF
Laboratory
•Hematology
–CBC, coagulation
•Biochemistry
–Blood glucose, BUN, creatinine, electrolyte, LFT
•Blood gas
•Virological markers
–Hepatitis profiles (A, B, C, delta)
•Microbiology
–Hemoculture
–Sputum/urine culture
Treatment
•Specific treatment
–Liver transplantation (stage 3 and 4)
•Complication treatment
–Hepatic encephalopathy
–Cerebral edema
–Sepsis
–Renal failure
–Circulatory dysfunction
–Coagulopathy
–Gastrointestinal bleeding
–Pulmonary complication
Complication treatment
•Hepatic encephalopathy
•↑ amonia WITHIN THE GUT LUMEN

•Concept
–Ammonia ↓
–Precipitating factors↓

•Restrict protein diet: 40 – 70 g/day
•Non-absorbable disaccharides: laculose
•Antibiotic: rifaximin, neomycin,
Complication treatment
•Cerebral edema
–Astrocyte edema
–Brainstem herniation, most causes of death
–Neurologic manifestations hypertonic, hyperflexia,
and altered pupillary responses

–Treatment:
•Elevated head position
•Manitol 0.5-1g/kg
ISCHEMIC HEPATITIS
(SHOCK LIVER, HYPOXIC
HEPATITIS)

ISCHEMIC HEPATITIS


•Ischemic hepatitis refers to diffuse hepatic
injury resulting from acute hypoperfusion



•Many cases of ischemic hepatitis occur in the
setting of congestive heart failure
ISCHEMIC HEPATITIS

•Clinical manifestations
–Any cause of shock or hemodynamic instability
can cause ischemic injury to the liver

–Ischemic injury can also be caused by focal
interruption of the hepatic blood supply

–The hemodynamic insult is usually apparent
clinically before evidence of liver injury appears
ISCHEMIC HEPATITIS

–Ischemic hepatitis is usually first detected because
of elevations in liver biochemical tests following a
hypotensive episode.

–Rare patients have symptoms suggesting acute
hepatitis, including nausea, vomiting, anorexia,
malaise, and right upper quadrant pain

–ischemia should always be considered in the
differential diagnosis of acute hepatitis, along with
more common causes such as viral infection,
ISCHEMIC HEPATITIS
•typical pattern of liver biochemical tests
consists of:

–rapid rise in serum aminotransferase levels
associated with an early massive rise in lactate
dehydrogenase (LDH) levels

–Peak aminotransferase levels are typically 25 to
250 times the upper limit of normal and are
reached within one to three days of the
hemodynamic insult

ISCHEMIC HEPATITIS
•Diagnosis

– There are relatively few causes of liver injury that
result in the striking increases in aminotransferase
levels

–Besides ischemic hepatitis, the most common are
acute viral hepatitis and acute drug- or toxin-
induced liver injury
ISCHEMIC HEPATITIS
•Pathology

–The histologic hallmark of ischemic hepatitis is
necrosis of hepatocytes
–associated with a variable degree of architectural
collapse around the central vein, depending upon
the duration and extent of ischemia

–There are characteristically few inflammatory cells
ISCHEMIC HEPATITIS
•Management
– aimed at restoring cardiac output and reversing
the underlying cause of hemodynamic instability.

•Prognosis:
– Ischemic hepatitis is nearly always benign and
self-limited.
–The severity of the liver injury correlates with the
duration and extent of the hemodynamic
compromise.
–Prognosis is mostly related to the severity of the
Drugs induced hepatitis

Drugs induced hepatitis

•Drug hepatotoxicity is the most common cause
of fulminant liver failure in the United States

•Hepatotoxicity can occur with many drugs by a
variety of mechanisms.
Drugs induced hepatitis

SPECTRUM OF DRUG-INDUCED
HEPATOTOXICITY
–A variety of clinical presentations may be seen in
patients who develop drug hepatotoxicity, ranging
from
•asymptomatic mild biochemical abnormalities to an
acute illness with jaundice that resembles viral hepatitis
Drugs induced hepatitis
SPECTRUM OF DRUG-INDUCED HEPATOTOXICITY
- Subclinical
- Acute hepatic injury
- Cytotoxic
- Cholestatic
- mixed patterns
- Steatosis
- Chronic hepatic injury
- Chronic hepatitis
- steatosis
- fibrosis and cirrhosis
- Vascular disease
- granulomatous disease
- Neoplasia
Drugs induced hepatitis
Subclinical

–Many drugs can induce asymptomatic elevations
in liver enzymes without producing overt clinical
disease
•antibiotics, antidepressants, antihyperlipidemics,
sulfonamides, salicylates, sulfonylureas, and quinidine

–Most elevations are benign and resolve once the
offending agent has been discontinued.
Drugs induced hepatitis
•Acute hepatic injury

–Cytotoxic
•hepatocellular injury is similar to that seen in viral
hepatitis and includes necrosis, steatosis, and cellular
degeneration.
• acetaminophen, phenytoin, methyldopa, diclofenac

–Cholestatic
•resembles extrahepatic obstructive jaundice
•chlorpromazine, trimethoprim-sulfamethoxazole,
rifampin, erythromycin, amiodarone
Drugs induced hepatitis
•Acute hepatic injury

–Mixed patterns
•often seen in patients with hepatotoxicity due to phenytoin
•Such patients may be at increased risk to develop chronic liver
disease compared with other forms of hepatotoxicity

– Steatosis
• Drug-induced acute steatosis is uncommon and occurs less often
than chronic steatosis.
•acute steatosis tends to be microvesicular
•tetracycline, amiodarone, piroxicam
Drugs induced hepatitis
•Chronic hepatic injury

62. causes
•Hepatitis viruses
–Hepatitis A most common acute viral hepatitis but
rare for acute infection to progress to ALF
–Hepatitis B most common viral cause ALF
•Drug and toxins
–Acetaminophen, alcohol, Amiodarone, halothane,
isoniazid, methyldopa, NSAIDS, phenytoin,
rifampicin, sufonamides, tetracycline, tricyclic
antidepressants, valpoic acid
causes
•Vascular
–Portal vein thrombosis
–Budd-Chiari syndrome
–Veno-occlusive disease
–Ischemic hepatitis
•Metabolic
–Wilson’s disease
–Acute fatty liver of pregnancy
–Reye’s syndrome
causes
•Miscellaneous
–Malignant infiltration of the liver
–Heat stroke
–Sepsis
–Autoimmune hepatitis
Acetaminophen toxicity
Very high AST and ALT (often >3500 IU/L)
High INR
Low bilirubin
Ischemic hepatic injury
Very high AST and ALT (25–250 times of upper limit of normal)
Elevated serum LDH
Hepatitis B virus
Aminotransferase levels: 1000–2000 IU/L
ALT usually > AST
Wilson disease
Coombs-negative hemolytic anemia
Aminotransferase levels <2000 IU/L
AST/ALT ratio >2
Markedly low ALP (<40 IU/L)
ALP/total bilirubin ratio <4
Rapidly progressive renal failure
Low uric acid levels
Acute fatty liver of pregnancy/HELLP syndrome
Aminotransferase levels <1000 IU/L
Elevated bilirubin
Low platelet count
Herpes simplex virus
Markedly elevated aminotransferases
Leukopenia
Low bilirubin
Reye syndrome/Valproate or doxycycline toxicity Minor to moderate elevations in aminotransferase and bilirubin levels
Sign and symptom
•Acute liver failure
–Nonspecific symptoms
–Malaise
–Nausea
–Jaundice
–Ecchymoses
–Etc…
FHF complication
•Hepatic encephalopathy
•Cerebral edema
•Sepsis
•Renal failure
•Circulatory dysfunction
•Coagulopathy
•Gastrointestinal bleeding
•Pulmonary complication
•Metabolic disturbance, metabolic acidosis,
hypoglycemia, hypophosphatemia
FHF
Laboratory
•Hematology
–CBC, coagulation
•Biochemistry
–Blood glucose, BUN, creatinine, electrolyte, LFT
•Blood gas
•Virological markers
–Hepatitis profiles (A, B, C, delta)
•Microbiology
–Hemoculture
–Sputum/urine culture
Treatment
•Specific treatment
–Liver transplantation (stage 3 and 4)
•Complication treatment
–Hepatic encephalopathy
–Cerebral edema
–Sepsis
–Renal failure
–Circulatory dysfunction
–Coagulopathy
–Gastrointestinal bleeding
–Pulmonary complication
Complication treatment
•Hepatic encephalopathy
•↑ amonia WITHIN THE GUT LUMEN

•Concept
–Ammonia ↓
–Precipitating factors↓

•Restrict protein diet: 40 – 70 g/day
•Non-absorbable disaccharides: laculose
•Antibiotic: rifaximin, neomycin,
Complication treatment
•Cerebral edema
–Astrocyte edema
–Brainstem herniation, most causes of death
–Neurologic manifestations hypertonic, hyperflexia,
and altered pupillary responses

–Treatment:
•Elevated head position
•Manitol 0.5-1g/kg
ISCHEMIC HEPATITIS
(SHOCK LIVER, HYPOXIC
HEPATITIS)

ISCHEMIC HEPATITIS


•Ischemic hepatitis refers to diffuse hepatic
injury resulting from acute hypoperfusion



•Many cases of ischemic hepatitis occur in the
setting of congestive heart failure
ISCHEMIC HEPATITIS

•Clinical manifestations
–Any cause of shock or hemodynamic instability
can cause ischemic injury to the liver

–Ischemic injury can also be caused by focal
interruption of the hepatic blood supply

–The hemodynamic insult is usually apparent
clinically before evidence of liver injury appears
ISCHEMIC HEPATITIS

–Ischemic hepatitis is usually first detected because
of elevations in liver biochemical tests following a
hypotensive episode.

–Rare patients have symptoms suggesting acute
hepatitis, including nausea, vomiting, anorexia,
malaise, and right upper quadrant pain

–ischemia should always be considered in the
differential diagnosis of acute hepatitis, along with
more common causes such as viral infection,
ISCHEMIC HEPATITIS
•typical pattern of liver biochemical tests
consists of:

–rapid rise in serum aminotransferase levels
associated with an early massive rise in lactate
dehydrogenase (LDH) levels

–Peak aminotransferase levels are typically 25 to
250 times the upper limit of normal and are
reached within one to three days of the
hemodynamic insult

ISCHEMIC HEPATITIS
•Diagnosis

– There are relatively few causes of liver injury that
result in the striking increases in aminotransferase
levels

–Besides ischemic hepatitis, the most common are
acute viral hepatitis and acute drug- or toxin-
induced liver injury
ISCHEMIC HEPATITIS
•Pathology

–The histologic hallmark of ischemic hepatitis is
necrosis of hepatocytes
–associated with a variable degree of architectural
collapse around the central vein, depending upon
the duration and extent of ischemia

–There are characteristically few inflammatory cells
ISCHEMIC HEPATITIS
•Management
– aimed at restoring cardiac output and reversing
the underlying cause of hemodynamic instability.

•Prognosis:
– Ischemic hepatitis is nearly always benign and
self-limited.
–The severity of the liver injury correlates with the
duration and extent of the hemodynamic
compromise.
–Prognosis is mostly related to the severity of the
Drugs induced hepatitis

Drugs induced hepatitis

•Drug hepatotoxicity is the most common cause
of fulminant liver failure in the United States

•Hepatotoxicity can occur with many drugs by a
variety of mechanisms.
Drugs induced hepatitis

SPECTRUM OF DRUG-INDUCED
HEPATOTOXICITY
–A variety of clinical presentations may be seen in
patients who develop drug hepatotoxicity, ranging
from
•asymptomatic mild biochemical abnormalities to an
acute illness with jaundice that resembles viral hepatitis
Drugs induced hepatitis
SPECTRUM OF DRUG-INDUCED HEPATOTOXICITY
- Subclinical
- Acute hepatic injury
- Cytotoxic
- Cholestatic
- mixed patterns
- Steatosis
- Chronic hepatic injury
- Chronic hepatitis
- steatosis
- fibrosis and cirrhosis
- Vascular disease
- granulomatous disease
- Neoplasia
Drugs induced hepatitis
Subclinical

–Many drugs can induce asymptomatic elevations
in liver enzymes without producing overt clinical
disease
•antibiotics, antidepressants, antihyperlipidemics,
sulfonamides, salicylates, sulfonylureas, and quinidine

–Most elevations are benign and resolve once the
offending agent has been discontinued.
Drugs induced hepatitis
•Acute hepatic injury

–Cytotoxic
•hepatocellular injury is similar to that seen in viral
hepatitis and includes necrosis, steatosis, and cellular
degeneration.
• acetaminophen, phenytoin, methyldopa, diclofenac

–Cholestatic
•resembles extrahepatic obstructive jaundice
•chlorpromazine, trimethoprim-sulfamethoxazole,
rifampin, erythromycin, amiodarone
Drugs induced hepatitis
•Acute hepatic injury

–Mixed patterns
•often seen in patients with hepatotoxicity due to phenytoin
•Such patients may be at increased risk to develop chronic liver
disease compared with other forms of hepatotoxicity

– Steatosis
• Drug-induced acute steatosis is uncommon and occurs less often
than chronic steatosis.
•acute steatosis tends to be microvesicular
•tetracycline, amiodarone, piroxicam
Drugs induced hepatitis
•Chronic hepatic injury

63. causes
•Hepatitis viruses
–Hepatitis A most common acute viral hepatitis but
rare for acute infection to progress to ALF
–Hepatitis B most common viral cause ALF
•Drug and toxins
–Acetaminophen, alcohol, Amiodarone, halothane,
isoniazid, methyldopa, NSAIDS, phenytoin,
rifampicin, sufonamides, tetracycline, tricyclic
antidepressants, valpoic acid
causes
•Vascular
–Portal vein thrombosis
–Budd-Chiari syndrome
–Veno-occlusive disease
–Ischemic hepatitis
•Metabolic
–Wilson’s disease
–Acute fatty liver of pregnancy
–Reye’s syndrome
causes
•Miscellaneous
–Malignant infiltration of the liver
–Heat stroke
–Sepsis
–Autoimmune hepatitis
Acetaminophen toxicity
Very high AST and ALT (often >3500 IU/L)
High INR
Low bilirubin
Ischemic hepatic injury
Very high AST and ALT (25–250 times of upper limit of normal)
Elevated serum LDH
Hepatitis B virus
Aminotransferase levels: 1000–2000 IU/L
ALT usually > AST
Wilson disease
Coombs-negative hemolytic anemia
Aminotransferase levels <2000 IU/L
AST/ALT ratio >2
Markedly low ALP (<40 IU/L)
ALP/total bilirubin ratio <4
Rapidly progressive renal failure
Low uric acid levels
Acute fatty liver of pregnancy/HELLP syndrome
Aminotransferase levels <1000 IU/L
Elevated bilirubin
Low platelet count
Herpes simplex virus
Markedly elevated aminotransferases
Leukopenia
Low bilirubin
Reye syndrome/Valproate or doxycycline toxicity Minor to moderate elevations in aminotransferase and bilirubin levels
Sign and symptom
•Acute liver failure
–Nonspecific symptoms
–Malaise
–Nausea
–Jaundice
–Ecchymoses
–Etc…
FHF complication
•Hepatic encephalopathy
•Cerebral edema
•Sepsis
•Renal failure
•Circulatory dysfunction
•Coagulopathy
•Gastrointestinal bleeding
•Pulmonary complication
•Metabolic disturbance, metabolic acidosis,
hypoglycemia, hypophosphatemia
FHF
Laboratory
•Hematology
–CBC, coagulation
•Biochemistry
–Blood glucose, BUN, creatinine, electrolyte, LFT
•Blood gas
•Virological markers
–Hepatitis profiles (A, B, C, delta)
•Microbiology
–Hemoculture
–Sputum/urine culture
Treatment
•Specific treatment
–Liver transplantation (stage 3 and 4)
•Complication treatment
–Hepatic encephalopathy
–Cerebral edema
–Sepsis
–Renal failure
–Circulatory dysfunction
–Coagulopathy
–Gastrointestinal bleeding
–Pulmonary complication
Complication treatment
•Hepatic encephalopathy
•↑ amonia WITHIN THE GUT LUMEN

•Concept
–Ammonia ↓
–Precipitating factors↓

•Restrict protein diet: 40 – 70 g/day
•Non-absorbable disaccharides: laculose
•Antibiotic: rifaximin, neomycin,
Complication treatment
•Cerebral edema
–Astrocyte edema
–Brainstem herniation, most causes of death
–Neurologic manifestations hypertonic, hyperflexia,
and altered pupillary responses

–Treatment:
•Elevated head position
•Manitol 0.5-1g/kg
ISCHEMIC HEPATITIS
(SHOCK LIVER, HYPOXIC
HEPATITIS)

ISCHEMIC HEPATITIS


•Ischemic hepatitis refers to diffuse hepatic
injury resulting from acute hypoperfusion



•Many cases of ischemic hepatitis occur in the
setting of congestive heart failure
ISCHEMIC HEPATITIS

•Clinical manifestations
–Any cause of shock or hemodynamic instability
can cause ischemic injury to the liver

–Ischemic injury can also be caused by focal
interruption of the hepatic blood supply

–The hemodynamic insult is usually apparent
clinically before evidence of liver injury appears
ISCHEMIC HEPATITIS

–Ischemic hepatitis is usually first detected because
of elevations in liver biochemical tests following a
hypotensive episode.

–Rare patients have symptoms suggesting acute
hepatitis, including nausea, vomiting, anorexia,
malaise, and right upper quadrant pain

–ischemia should always be considered in the
differential diagnosis of acute hepatitis, along with
more common causes such as viral infection,
ISCHEMIC HEPATITIS
•typical pattern of liver biochemical tests
consists of:

–rapid rise in serum aminotransferase levels
associated with an early massive rise in lactate
dehydrogenase (LDH) levels

–Peak aminotransferase levels are typically 25 to
250 times the upper limit of normal and are
reached within one to three days of the
hemodynamic insult

ISCHEMIC HEPATITIS
•Diagnosis

– There are relatively few causes of liver injury that
result in the striking increases in aminotransferase
levels

–Besides ischemic hepatitis, the most common are
acute viral hepatitis and acute drug- or toxin-
induced liver injury
ISCHEMIC HEPATITIS
•Pathology

–The histologic hallmark of ischemic hepatitis is
necrosis of hepatocytes
–associated with a variable degree of architectural
collapse around the central vein, depending upon
the duration and extent of ischemia

–There are characteristically few inflammatory cells
ISCHEMIC HEPATITIS
•Management
– aimed at restoring cardiac output and reversing
the underlying cause of hemodynamic instability.

•Prognosis:
– Ischemic hepatitis is nearly always benign and
self-limited.
–The severity of the liver injury correlates with the
duration and extent of the hemodynamic
compromise.
–Prognosis is mostly related to the severity of the
Drugs induced hepatitis

Drugs induced hepatitis

•Drug hepatotoxicity is the most common cause
of fulminant liver failure in the United States

•Hepatotoxicity can occur with many drugs by a
variety of mechanisms.
Drugs induced hepatitis

SPECTRUM OF DRUG-INDUCED
HEPATOTOXICITY
–A variety of clinical presentations may be seen in
patients who develop drug hepatotoxicity, ranging
from
•asymptomatic mild biochemical abnormalities to an
acute illness with jaundice that resembles viral hepatitis
Drugs induced hepatitis
SPECTRUM OF DRUG-INDUCED HEPATOTOXICITY
- Subclinical
- Acute hepatic injury
- Cytotoxic
- Cholestatic
- mixed patterns
- Steatosis
- Chronic hepatic injury
- Chronic hepatitis
- steatosis
- fibrosis and cirrhosis
- Vascular disease
- granulomatous disease
- Neoplasia
Drugs induced hepatitis
Subclinical

–Many drugs can induce asymptomatic elevations
in liver enzymes without producing overt clinical
disease
•antibiotics, antidepressants, antihyperlipidemics,
sulfonamides, salicylates, sulfonylureas, and quinidine

–Most elevations are benign and resolve once the
offending agent has been discontinued.
Drugs induced hepatitis
•Acute hepatic injury

–Cytotoxic
•hepatocellular injury is similar to that seen in viral
hepatitis and includes necrosis, steatosis, and cellular
degeneration.
• acetaminophen, phenytoin, methyldopa, diclofenac

–Cholestatic
•resembles extrahepatic obstructive jaundice
•chlorpromazine, trimethoprim-sulfamethoxazole,
rifampin, erythromycin, amiodarone
Drugs induced hepatitis
•Acute hepatic injury

–Mixed patterns
•often seen in patients with hepatotoxicity due to phenytoin
•Such patients may be at increased risk to develop chronic liver
disease compared with other forms of hepatotoxicity

– Steatosis
• Drug-induced acute steatosis is uncommon and occurs less often
than chronic steatosis.
•acute steatosis tends to be microvesicular
•tetracycline, amiodarone, piroxicam
Drugs induced hepatitis
•Chronic hepatic injury

64. causes
•Hepatitis viruses
–Hepatitis A most common acute viral hepatitis but
rare for acute infection to progress to ALF
–Hepatitis B most common viral cause ALF
•Drug and toxins
–Acetaminophen, alcohol, Amiodarone, halothane,
isoniazid, methyldopa, NSAIDS, phenytoin,
rifampicin, sufonamides, tetracycline, tricyclic
antidepressants, valpoic acid
causes
•Vascular
–Portal vein thrombosis
–Budd-Chiari syndrome
–Veno-occlusive disease
–Ischemic hepatitis
•Metabolic
–Wilson’s disease
–Acute fatty liver of pregnancy
–Reye’s syndrome
causes
•Miscellaneous
–Malignant infiltration of the liver
–Heat stroke
–Sepsis
–Autoimmune hepatitis
Acetaminophen toxicity
Very high AST and ALT (often >3500 IU/L)
High INR
Low bilirubin
Ischemic hepatic injury
Very high AST and ALT (25–250 times of upper limit of normal)
Elevated serum LDH
Hepatitis B virus
Aminotransferase levels: 1000–2000 IU/L
ALT usually > AST
Wilson disease
Coombs-negative hemolytic anemia
Aminotransferase levels <2000 IU/L
AST/ALT ratio >2
Markedly low ALP (<40 IU/L)
ALP/total bilirubin ratio <4
Rapidly progressive renal failure
Low uric acid levels
Acute fatty liver of pregnancy/HELLP syndrome
Aminotransferase levels <1000 IU/L
Elevated bilirubin
Low platelet count
Herpes simplex virus
Markedly elevated aminotransferases
Leukopenia
Low bilirubin
Reye syndrome/Valproate or doxycycline toxicity Minor to moderate elevations in aminotransferase and bilirubin levels
Sign and symptom
•Acute liver failure
–Nonspecific symptoms
–Malaise
–Nausea
–Jaundice
–Ecchymoses
–Etc…
FHF complication
•Hepatic encephalopathy
•Cerebral edema
•Sepsis
•Renal failure
•Circulatory dysfunction
•Coagulopathy
•Gastrointestinal bleeding
•Pulmonary complication
•Metabolic disturbance, metabolic acidosis,
hypoglycemia, hypophosphatemia
FHF
Laboratory
•Hematology
–CBC, coagulation
•Biochemistry
–Blood glucose, BUN, creatinine, electrolyte, LFT
•Blood gas
•Virological markers
–Hepatitis profiles (A, B, C, delta)
•Microbiology
–Hemoculture
–Sputum/urine culture
Treatment
•Specific treatment
–Liver transplantation (stage 3 and 4)
•Complication treatment
–Hepatic encephalopathy
–Cerebral edema
–Sepsis
–Renal failure
–Circulatory dysfunction
–Coagulopathy
–Gastrointestinal bleeding
–Pulmonary complication
Complication treatment
•Hepatic encephalopathy
•↑ amonia WITHIN THE GUT LUMEN

•Concept
–Ammonia ↓
–Precipitating factors↓

•Restrict protein diet: 40 – 70 g/day
•Non-absorbable disaccharides: laculose
•Antibiotic: rifaximin, neomycin,
Complication treatment
•Cerebral edema
–Astrocyte edema
–Brainstem herniation, most causes of death
–Neurologic manifestations hypertonic, hyperflexia,
and altered pupillary responses

–Treatment:
•Elevated head position
•Manitol 0.5-1g/kg
ISCHEMIC HEPATITIS
(SHOCK LIVER, HYPOXIC
HEPATITIS)

ISCHEMIC HEPATITIS


•Ischemic hepatitis refers to diffuse hepatic
injury resulting from acute hypoperfusion



•Many cases of ischemic hepatitis occur in the
setting of congestive heart failure
ISCHEMIC HEPATITIS

•Clinical manifestations
–Any cause of shock or hemodynamic instability
can cause ischemic injury to the liver

–Ischemic injury can also be caused by focal
interruption of the hepatic blood supply

–The hemodynamic insult is usually apparent
clinically before evidence of liver injury appears
ISCHEMIC HEPATITIS

–Ischemic hepatitis is usually first detected because
of elevations in liver biochemical tests following a
hypotensive episode.

–Rare patients have symptoms suggesting acute
hepatitis, including nausea, vomiting, anorexia,
malaise, and right upper quadrant pain

–ischemia should always be considered in the
differential diagnosis of acute hepatitis, along with
more common causes such as viral infection,
ISCHEMIC HEPATITIS
•typical pattern of liver biochemical tests
consists of:

–rapid rise in serum aminotransferase levels
associated with an early massive rise in lactate
dehydrogenase (LDH) levels

–Peak aminotransferase levels are typically 25 to
250 times the upper limit of normal and are
reached within one to three days of the
hemodynamic insult

ISCHEMIC HEPATITIS
•Diagnosis

– There are relatively few causes of liver injury that
result in the striking increases in aminotransferase
levels

–Besides ischemic hepatitis, the most common are
acute viral hepatitis and acute drug- or toxin-
induced liver injury
ISCHEMIC HEPATITIS
•Pathology

–The histologic hallmark of ischemic hepatitis is
necrosis of hepatocytes
–associated with a variable degree of architectural
collapse around the central vein, depending upon
the duration and extent of ischemia

–There are characteristically few inflammatory cells
ISCHEMIC HEPATITIS
•Management
– aimed at restoring cardiac output and reversing
the underlying cause of hemodynamic instability.

•Prognosis:
– Ischemic hepatitis is nearly always benign and
self-limited.
–The severity of the liver injury correlates with the
duration and extent of the hemodynamic
compromise.
–Prognosis is mostly related to the severity of the
Drugs induced hepatitis

Drugs induced hepatitis

•Drug hepatotoxicity is the most common cause
of fulminant liver failure in the United States

•Hepatotoxicity can occur with many drugs by a
variety of mechanisms.
Drugs induced hepatitis

SPECTRUM OF DRUG-INDUCED
HEPATOTOXICITY
–A variety of clinical presentations may be seen in
patients who develop drug hepatotoxicity, ranging
from
•asymptomatic mild biochemical abnormalities to an
acute illness with jaundice that resembles viral hepatitis
Drugs induced hepatitis
SPECTRUM OF DRUG-INDUCED HEPATOTOXICITY
- Subclinical
- Acute hepatic injury
- Cytotoxic
- Cholestatic
- mixed patterns
- Steatosis
- Chronic hepatic injury
- Chronic hepatitis
- steatosis
- fibrosis and cirrhosis
- Vascular disease
- granulomatous disease
- Neoplasia
Drugs induced hepatitis
Subclinical

–Many drugs can induce asymptomatic elevations
in liver enzymes without producing overt clinical
disease
•antibiotics, antidepressants, antihyperlipidemics,
sulfonamides, salicylates, sulfonylureas, and quinidine

–Most elevations are benign and resolve once the
offending agent has been discontinued.
Drugs induced hepatitis
•Acute hepatic injury

–Cytotoxic
•hepatocellular injury is similar to that seen in viral
hepatitis and includes necrosis, steatosis, and cellular
degeneration.
• acetaminophen, phenytoin, methyldopa, diclofenac

–Cholestatic
•resembles extrahepatic obstructive jaundice
•chlorpromazine, trimethoprim-sulfamethoxazole,
rifampin, erythromycin, amiodarone
Drugs induced hepatitis
•Acute hepatic injury

–Mixed patterns
•often seen in patients with hepatotoxicity due to phenytoin
•Such patients may be at increased risk to develop chronic liver
disease compared with other forms of hepatotoxicity

– Steatosis
• Drug-induced acute steatosis is uncommon and occurs less often
than chronic steatosis.
•acute steatosis tends to be microvesicular
•tetracycline, amiodarone, piroxicam
Drugs induced hepatitis
•Chronic hepatic injury