19 hepatic cirrhosis

1. Hepatic Cirrhosis
Bin Wu, MD & PhD
Professor and Head
Department of Gastroenterology
The Third Affiliated Hospital
Sun Yat-Sen University

2. Aim:
Master: Clinical Manifestation and
Diagnosis of Hepatic cirrhosis
Acquaint: Distinguish Diagnosis and
Complication as well as Rule of
Treatment
Know: Causes and Risk Factors, Mechanism.
Times: 2 hours

3. Definition
Hepatic cirrhosis is a chronic,
degenerative disease in which normal
liver cells are damaged and are then
replaced by scar tissue.

4. Description
Hepatic Cirrhosis changes the
structure of the liver and the blood
vessels that nourish it. The disease
reduces the liver's ability to
manufacture proteins and process
hormones, nutrients, medications,
and poisons.

5. Cirrhosis gets worse over time and
can become potentially life injury.
This disease can cause:
4. Excessive bleeding (hemorrhage)
5. Impotence
6. Liver cancer
7. Coma due to accumulated ammonia

and body wastes (liver failure)
5. Death

6. Long-term alcoholism is the primary
cause of cirrhosis in the United States. Men
and women respond differently to alcohol.
Although most men can safely consume two
to five drinks a day, one to two drinks a day
can cause liver damage in women.
Individual tolerance to alcohol varies, but
people who drink more and drink more
often have a higher risk of developing
cirrhosis. In some people, one drink a day
can cause liver scarring.

7. Chronic liver infections, such as hepatitis B
and particularly hepatitis C, are commonly linked
to cirrhosis. People at high risk of contracting
hepatitis B include those exposed to the virus
through contact with blood and body fluids. This
includes healthcare workers and intravenous (IV)
drug users. In the past, people have contracted
hepatitis C through blood transfusions. As of
2003, cirrhosis resulting from chronic hepatitis
has emerged as a leading cause of death among
HIV-positive patients; in Europe, about 30% of
HIV-positive patients are coinfected with a
hepatitis virus.

8. Liver injury, reactions to prescription
medications, certain autoimmune disorders,
exposure to toxic substances, and repeated
episodes of heart failure with liver
congestion can cause cirrhosis. A family
history of diseases can genetically
predispose a person to develop cirrhosis.

9. Cirrhosis is the seventh leading
cause of disease related death in the
United States. It is twice as common
in men as in women. The disease
occurs in more than half of all chronic
alcoholics and kills about 25,000
peoples a year. It is the third most
common cause of death in adults
between the ages of 45 and 65.

10. Hepatitis is the first leading
cause of disease related death in the
China. So far, HBsAg
+
peoples are
about 1200 million (1, 200, 000, 000),
and peoples who are infected HCV are
about 38 million (38, 000, 000).

11. Types of cirrhosis
Portal or nutritional cirrhosis is the form of the disease
most common in the United States. About 30–50% of all cases of
cirrhosis are this type. Nine out of every 10 people who have
nutritional cirrhosis have a history of alcoholism.
Biliary cirrhosis is caused by intrahepatic bile-duct diseases
that impede bile flow. Bile is formed in the liver and is carried by
ducts to the intestines. Bile then helps digest fats in the intestines.
Biliary cirrhosis can scar or block these ducts. It represents 15–
20% of all cirrhosis.
Various types of chronic hepatitis, especially hepatitis B
and hepatitis C, can cause post-necrotic cirrhosis. This form of the
disease affects up to 40% of all patients who have cirrhosis.

12. Chronic hepatitis B and C
Alcoholic liver disease
Drugs or toxins
Cardiac cirrhosis (heart failure )
Certain parasitic infections (such as schistosomiasis)
Primary biliary cirrhosis
Autoimmune hepatitis
Primary sclerosing cholangitis
Other: such as Wilson's disease, Hereditary
Hemochromatosis, Alpha 1-antitrypsin deficiency,
Galactosemia, Cystic fibrosis
In China, the chronic hepatitis is common cause, but
not the alcoholic liver disease.
Risk factors of Hepatic cirrhosis

13. Worldwide Prevalence of HBV Worldwide Prevalence of HBV
and Incidence of HCCand Incidence of HCC
World prevalence of HBV carriers
HBsAg carriers-prevalence
<2%
2–7%
>8%
Poorly documented
Annual incidence of primary HCC
Cases/100,000 population
1–3
3–10
10–150
Poorly documented

WHO 2003

14. Hepatitis B Related Death in ChinaHepatitis B Related Death in China
Per 100,000 person/yr
101.316.0113Women
81.726.7193Men
81.521.3306Total
Chronic liver
diseases*
Rank orderPercentage of
total death
MortalityNo. of DeathsCause of death
* >85% related to HBV infection He et al. NEJM 2006

15. •Hepatitis B is a viral infection that attacks the liver and can
cause both acute and chronic disease.
•The virus is transmitted through contact with the blood or
other body fluids of an infected person - not through casual
contact.
•About 2 billion peoples worldwide have been infected with
the virus and about 350 million live with chronic infection.
An estimated 600 000 persons die each year due to the acute
or chronic consequences of hepatitis B.
•About 25% of adults who become chronically infected during
childhood later die from liver cancer or cirrhosis (scarring of
the liver) caused by the chronic infection.
•The hepatitis B virus is 50 to 100 times more infectious than
HIV.
•Hepatitis B virus is an important occupational hazard for
health workers.
•Hepatitis B is preventable with a safe and effective vaccine.
Data is from WHO

17. Hepatocytes necrosis
Hepatocytes regeneration
Fibrotic scar tissue
Regenerative nodules form
VirusAlcoholOther

19. Cirrhosis of Liver
Spleen
Cirrhosis of Liver
Nodular

21. This liver is slightly enlarged and has a
pale yellow appearance, seen both on the
capsule and cut surface. This uniform
change is consistent with fatty
metamorphosis (fatty change).
Here are seen the lipid vacuoles within
hepatocytes. The lipid accumulates
when lipoprotein transport is disrupted
and/or when fatty acids accumulate.
Alcohol, the most common cause, is a
hepatotoxin that interferes with
mitochondrial and microsomal function
in hepatocytes, leading to an
accumulation of lipid.
Fatty Liver
H&E
Fatty Liver
lipid vacuoles
Healthy

23. Normal liver
Cirrhosis after hepatitis
Cirrhosis after fatty liver
Regenerative nodules
Fibrotic scar tissue
Hepatic lobule
Centre vein
Fatty granule
Hepatic cord

24. CBDL TAA
CCl4 TAA

25. Pathology
Type of hepatic cirrhosis:
•Macronodular cirrhosis, ф>3.0 mm
•Micronodular cirrhosis, ф<3.0 mm
•Mix: Macro- +Micro-nodular cirrhosis

26. Ongoing liver damage with liver cell
necrosis followed by fibrosis and
hepatocyte regeneration results in
cirrhosis. This produces a nodular,
firm liver. The nodules seen here are
larger than 3 mm and, hence, this is an
example of macronodular cirrhosis.
This is an example of a micronodular
cirrhosis. The regenerative nodules
are quite small, averaging less than 3
mm in size. The most common cause
for this is chronic alcoholism. The
process of cirrhosis develops over
many years.
Macronodular cirrhosis Micronodular cirrhosis
>3.0mm <3.0mm
Mix is including maro- and micronodular cirrhosis
Pathology

27. Clinical Manifestation
Compensation Stage: The signs and symptoms of cirrhosis
are nonspecific and frequently related to the complications.
anemia
bleeding gums
constipation
decreased interest in sex
diarrhea
dull abdominal pain
dry skin and itching
fatigue
fever
fluid in the lungs
hallucinations
indigestion
lethargy
lightheadedness
loss of appetite
muscle weakness
musty breath
nausea
neuritis
vomiting
weakness
weight loss

28. Decompensation
1. Common symptom:
•Fatigue
•Lethargy
•Weakness
•weight loss
•Fever
•Dark yellow or brown urine
2. Digest system symptoms
•Diarrhea
•Constipation
•Dull abdominal pain
•Indigestion
•Nausea
1.Anemia and bleeding
•Anemia
•bleeding gums
5.Hypoendocrinism
•Decreased interest in sex
•women may have menstrual
irregularities
•Gynaecomastia
•Spider nevi
•Palmar erythema
Disfunction of liver:

29. Portal hypertension:
3.Esophageal and gastric varices
4.Ascites
5.Legs edema
6.Spleen enlarges
7.Abdomen varices
8.The liver enlarges during the early stages of illness
9.The liver dwindles during the later stages of illness

Decompensation

30. Jaundice is a condition in which a person's
skin and the whites of the eyes are
discolored yellow due to an increased level
of bile pigments in the blood resulting from
liver disease. Jaundice is sometimes called
icterus, from a Greek word for the
condition.

31. Many of these outward-bound chemicals
are excreted into the bile. One particular
substance, bilirubin, is yellow. Bilirubin is a
product of the breakdown of hemoglobin, which
is the protein inside red blood cells. If bilirubin
cannot leave the body, it accumulates and
discolors other tissues. The normal total level of
bilirubin in blood serum is between 0.2 mg/dL
and 1.2 mg/dL. When it rises to 3 mg/dL or
higher, the person's skin and the whites of the
eyes become noticeably yellow.

32. Jaundice, a yellow discoloration of all tissues
and organs, including the eye and the skin.

33. After liver is damaged, the hepatocytes are
not able to treat estrogen, resulting in Spider
nevi and Palmar erythema.

34. Spider nevi

35. Palmar erythema

36. As the liver becomes fibrotic, there is
obstruction of the blood flow through the liver.
This results in portal hypertension, an increase in
blood pressure within the portal vein and its
tributaries. The obstructed hepatic blood flow
also causes congestion of the spleen, leading to a
markedly enlarged spleen (splenomegaly). Also,
most people with cirrhosis eventually develop
fluid in their abdomen (ascites) and are at an
increased risk of developing a spontaneous
intraabdominal infection.

37. Ascites

38. Ascites Legs edema

39. Cirrhosis of Liver
Spleen enlarges
Cirrhosis of Liver

40. Portal hypertension results from the
abnormal blood flow pattern in liver
created by cirrhosis. The increased
pressure is transmitted to collateral
venous channels. Sometimes these venous
collaterals are dilated. Seen here is "caput
medusae" which consists of dilated veins
seen on the abdomen of a patient with
cirrhosis of the liver.
A much more serious problem
produced by portal hypertension results
when submucosal veins in the
esophagus become dilated. These are
known as esophageal varices. Varices
are seen here in the lower esophagus as
linear blue dilated veins. There is
hemorrhage around one of them. Such
varices are easily eroded, leading to
massive gastrointestinal hemorrhage
Abdomen varices Esophageal varices

41. Esophageal varices
Red spot

42. Esophageal varices

43. Gastric varices

44. Image of portal hypertensive
gastropathy seen on
endoscopy of the stomach.
The normally smooth mucosa
of the stomach has developed
a mosaic like appearance,
that resembles snake-skin

45. gastric antral vascular ectasia

46. Complications
1. Esophageal and gastric variceal bleeding
2.　Hepatic encephalopathy
3.　Infection
4.　Hepatocellular carcinoma
5.　Hepatorenal syndrome
6.　Hepatopulmonary syndrome
7.　Portal vein thrombus

47. Esophageal variceal bleeding

48. Hepatocellular carcinoma

49. Hepatocellular carcinoma

50. Portal vein stenosis

51. Portal vein thrombus

52. Lab findings
Aminotransferases - AST and ALT are moderately elevated, with AST > ALT.
However, normal aminotransferases do not preclude cirrhosis.
Alkaline phosphatase – (AKP)usually slightly elevated.
GGT -- correlates with AP levels. Typically much higher in chronic liver disease
from alcohol.
Bilirubin - may elevate as cirrhosis progresses.
Albumin - levels fall as the synthetic function of the liver declines with
worsening cirrhosis since albumin is exclusively synthesized in the liver
Prothrombin time - increases since the liver synthesizes clotting factors.
Globulins - increased due to shunting of bacterial antigens away from the liver
to lymphoid tissue.
Serum sodium - hyponatremia due to inability to excrete free water resulting
from high levels of ADH and aldosterone.
Thrombocytopenia - due to both congestive splenomegaly as well as decreased
thrombopoietin from the liver. However this rarely results in platelet count <
50,000/mL.
Leukopenia and neutropenia - due to splenomegaly with splenic margination.
Coagulation defects - the liver produces most of the coagulation factors and
thus coagulopathy correlates with worsening liver disease.

53. Other laboratory studies performed in
newly diagnosed cirrhosis may include:
Serology for hepatitis viruses, autoantibodies (ANA,
anti-smooth muscle, anti-mitochondria, anti-LKM)
Ferritin and transferrin saturation (markers of iron
overload), copper and ceruloplasmin (markers of
copper overload)
Immunoglobulin levels (IgG, IgM, IgA) - these are
non-specific but may assist in distinguishing various
causes
Cholesterol and glucose
Alpha 1-antitrypsin

54. Imaging
Ultrasound , CT and MRI
are routinely used in the evaluation of cirrhosis,
where it may show a small and nodular liver in
advanced cirrhosis along with increased echogenicity
with irregular appearing areas. Ultrasound may also
screen for hepatocellular carcinoma, portal
hypertension and Budd-Chiari syndrome (by
assessing flow in the hepatic vein).

56. MRIMRI
Ascites
Hepatic cirrhosis
Enlarged spleen

57. DSA DSA
Portal vein

58. Laparoscope can observe hepatic regenerative
nodular, and get liver biopsy sample.
Cirrhosis of Liver
Spleen enlarges

59. Endoscopy
Gastroscopy (endoscopic examination of the
esophagus, stomach and duodenum) is performed in
patients with established cirrhosis to exclude the
possibility of esophageal varices. If these are found,
prophylactic local therapy may be applied
(sclerotherapy or banding) and beta blocker
treatment may be commenced.

60. Esophageal varices

61. Portal hypertensive gastropathy

62. Liver biopsy:
The gold standard for diagnosis of cirrhosis is a
liver biopsy, through a percutaneous,
transjugular, laparoscopic, or fine-needle
approach. However, a biopsy is not necessary if
the clinical, laboratory, and radiologic data
suggests cirrhosis. Furthermore, there is a
small but significant risk to liver biopsy, and
cirrhosis itself predisposes for complications
due to liver biopsy.

63. A patient's medical history can reveal
illnesses or lifestyles likely to lead to cirrhosis.
Liver changes can be seen during a physical
examination. A doctor who suspects cirrhosis
may order blood and urine tests to measure liver
function. Because only a small number of healthy
cells are needed to carry out essential liver
functions, test results may be normal even when
cirrhosis is present.
Diagnosis

64. In about 10 out of every 100 patients,
the cause of cirrhosis cannot be determined.
Many people who have cirrhosis do not have
any symptoms (often called compensated
cirrhosis). Their disease is detected during a
routine physical or when tests for an
unrelated medical problem are performed.
This type of cirrhosis can also be detected
when complications occur (decompensated
cirrhosis).

65. Computed tomography scans (CT),
ultrasound, and other imaging techniques
can be used during diagnosis. They can
help determine the size of the liver, indicate
healthy and scarred areas of the organ, and
detect gallstones. Cirrhosis is sometimes
diagnosed during surgery or by examining
the liver with a laparoscope. This viewing
device is inserted into the patient's body
through a tiny incision in the abdomen.

66. Liver biopsy is usually needed to
confirm a diagnosis of cirrhosis. In this
procedure, a tissue sample is removed from
the liver and examined under a microscope
in order to learn more about the organ's
condition and to properly diagnose it.

67. A newer and less invasive test involves
the measurement of hyaluronic acid (HA) in
the patient's blood serum. As of 2003,
however, the serum HA test is most useful
in monitoring the progress of liver disease; it
is unlikely to completely replace liver biopsy
in the diagnosis of cirrhosis.

68. Prevention
Eliminating alcohol abuse could prevent 75–80% of all cases of cirrhosis.
Other preventive measures include:
Maintaining a healthy diet that includes whole foods and grains, vegetable,
and fruits
Obtaining counseling or other treatment for alcoholism
Taking precautions (practicing safe sex, avoiding dirty needles) to prevent
hepatitis
Getting immunizations against hepatitis if a person is in a high-risk group
receiving appropriate medical treatment quickly when diagnosed with hepatitis
B or hepatitis C
Having blood drawn at regular intervals to rid the body of excess iron from
hemochromatosis
Using medicines (chelating agents) to rid the body of excess copper from
Wilson's disease
Wearing protective clothing and following product directions when using toxic
chemicals at work, at home, or in the garden

69. General treatment
1. Etiological treatment
No drink alcoholic
Treatment of HBV and HCV
and so on
7.Protecting liver treatment
8.Treatment of ascites
9.Treatment of jaundice

70. 1.Common treatment: Rest, nutritional and supportable therapy.
2.Treating underlying causes: Alcoholic cirrhosis caused by
alcohol abuse is treated by abstaining from alcohol. Treatment
for hepatitis-related cirrhosis involves medications used to treat
the different types of hepatitis, such as interferon for viral
hepatitis and corticosteroids for autoimmune hepatitis.
Cirrhosis caused by Wilson's disease, in which copper builds
up in organs, is treated with chelation therapy (e.g.
penicillamine) to remove the copper.
3.Preventing further liver damage: Drug application of
ameliorate liver function.
4.Treatment of complications: Please see other part.
5.Surgery treatment: Please see surgery
6.Transplantation: If complications cannot be controlled or when
the liver ceases functioning, liver transplantation is necessary.

71. The therapy of cirrhosis is aimed primarily at
preventing or reducing the complications.
Bleeding esophageal varices (collateral venous
channels) are a frequent serious complication of
cirrhosis. Various techniques are used to control
the bleeding. In some individuals with severe
portal hypertension, vascular shunts are made to
reduce the pressure in the portal vein by
bypassing the liver. Most frequently the portal
vein is surgically connected to the
inferior vena cava so that some of the blood in the
portal vein does not pass through the liver.
Treatment

72. EEndoscope band ligationndoscope band ligation ( (EBLEBL) can prevent ) can prevent
and treat and treat Esophageal and gastric varices or
with bleeding

74. Ref: De Franchis R. Digestive and liver disease 2004;36(S1):S93Ref: De Franchis R. Digestive and liver disease 2004;36(S1):S93
Endoscopic sclerotherapy (EST) is an
established method for controlling and
preventing bleeding from oesophageal varices

75. Endoscopic sclerotherapy (EST)

76. AT Injection

77. Portal hypertension
Portal vein
Vena cava

78. Distal Splenorenal ShuntDistal Splenorenal Shunt

79. Harvard
University

80. Harvard
University

81. Harvard
University

82. Harvard Medical
School

83. The Third Affiliated Hospital
Sun Yat-Sen University

84. Position Open
Postdoctoral Fellow
Ph.D. Program
Master’s Program