Hepatitis Acute versus Chronic Causes Pathophysiology.pdf

Acute inflammation of the liver parenchyma.
Acute inflammatory cell infiltration
Inflammatory exudates and oedema
Swelling of cells, balloon degeneration
→ All result in organomegaly

In severe organ inflammation:
Widespread cell damage and cell death
Organ shrinkage
Features of organ failure (hepatic failure)
disorientation, confusion, coma
deepening jaundice
bleeding manifestation

Persistant hepatocyte injury
Alcohol, virus, drugs, toxins, genetic etc.
Chronic inflammation – chronic hepatitis
Cell necrosis + Fibrosis
Bridging fibrosis.
Regeneration of remaining hepatocytes forming nodules.
Loss of vascular arrangement results in regenerating hepatocytes ineffective.

Causes of acute hepatitis:
Hepatotrophic viruses: Hepatitis A virus (HAV)
Hepatitis B virus (HBV)
Hepatitis C virus (HCV)
Hepatitis D virus (HDV)
Hepatitis E virus (HEV)

Other viruses: Cytomegalovirus (CMV) Epstein-Barr virus (EBV) Yellow fever virus Dengue virus
Herpes simplex

Drugs:
Pyrazinamide, INH
Paracetamol
NSAIDs
Clavaulanic acid
Valproic acid
Alcohol
Helothene
Trauma
Disseminated intravascular coagulation (DIC)
Infarction

Causes of acute hepatitis:
Virus: HAV, HBV, HCV, HDV, HEV, CMV, EMV, Flabivirus
Drug: paracetamol, INH, pyrazinamide, NSAIDs, valproic acid etc.
Alcohol
Infarction/Trauma
DIC
Rare: Wilson’s disease, autoimmune

Causes of chronic hepatitis:
Virus: HBV, HCV, HDV
Drug: methotrexate
Alcohol
Fatty liver (NAFLD)
Biliary stasis: PBC, PSC, cystic fibrosis
Genetic: Wilson’s disease, haemochromatosis, α-1ATD
Autoimmune
Venous stasis: Budd-Chiary syndrome, CHF

Virus Hepatitis A Hepatitis B Hepatitis C Hepatitis D Hepatitis E
Nucleic acid RNA DNA RNA RNA RNA
Incubation 2-4 weeks 4-20 weeks 2-26 weeks 6-9 weeks 3-8 weeks
Spread Fecal-oral Blood Blood Blood Fecal-oral
Chronicity No Yes Yes Yes
(ē HBV) No
Vaccine Yes Yes No HBV vaccine No

Clinical features of acute hepatitis Symptoms):
Asymptomatic
Prodromal symptoms: weakness, myalgia, arthralgia, headache
GI symptoms: anorexia, nausea, vomiting, lose stool, constipation, abdominal discomfort/pain
Yellow urine, yellow eyes (jaundice)
Features of cholestasis: pruritus, pale stool, deep jaundice

Clinical features of acute hepatitis (signs):
Jaundice
Tender hepatomegaly
Ill looking
Scratch marks for pruritus
Splenomegaly
Features of complications: Hepatic failure, bleeding, infection

Complications:
Acute liver failure/Fulminant HF (esp. AVH in pregnancy)
Hepato-renal syndrome
Hypoglycaemia
Cholestatic hepatitis (hepatitis A)
Aplastic anaemia
Chronic liver disease and cirrhosis (hepatitis B and C)
Relapsing hepatitis

Investigations:
Liver function tests:
SGPT, SGOT
Serum bilirubin
Prothrombin time
Viral markers:
- HBsAg, Anti-HEV IgM, Anti-HAV IgM, Anti-HCV
USG of liver:
- Hypoechoic liver parenchyma
Others:
- CBC, Blood sugar, RFT, electrolytes etc.

Management:
General measures:
1. Complete bed rest
2. Nutrition: normal d

1. ACUTE HEPATITIS
(vs. Chronic
Hepatitis)
Dr. A. B. M. Adnan
Associate Professor, Hepatology

2. Pathophysiology:
Acute Hepatitis (mild)
 Acute inflammation of the liver parenchyma.
 Acute inflammatory cell infiltration
 Inflammatory exudates and oedema
 Swelling of cells, balloon degeneration
→ All result in organomegaly

3. Pathophysiology:
Acute Hepatitis (severe)
In severe organ inflammation:
Widespread cell damage and cell death
Organ shrinkage
Features of organ failure (hepatic failure)
•disorientation, confusion, coma
•deepening jaundice
• bleeding manifestation

4. Pathophysiology:
Chronic Hepatitis
•Persistant hepatocyte injury
–Alcohol, virus, drugs, toxins, genetic etc.
•Chronic inflammation – chronic hepatitis
–Cell necrosis + Fibrosis
•Bridging fibrosis.
•Regeneration of remaining hepatocytes
forming nodules.
•Loss of vascular arrangement results in
regenerating hepatocytes ineffective.

5. Acute - Hepatitis - Chronic

6. Normal Liver - Microscopy

7. Liver Biopsy – CPH:

8. Causes of Acute Hepatitis
A.Viral causes
B.Non-viral causes

9. Viral Causes
of Acute Hepatitis
Hepatotrophic viruses:Hepatitis A virus (HAV)
Hepatitis B virus (HBV)
Hepatitis C virus (HCV)
Hepatitis D virus (HDV)
Hepatitis E virus (HEV)
Other viruses: Cytomegalovirus (CMV)
Epstein-Barr virus (EBV)
Yellow fever virus
Dengue virus
Herpes simplex

10. Non-viral Causes
of Acute Hepatitis
1.Drugs:
–Pyrazinamide, INH
–Paracetamol
–NSAIDs
–Clavaulanic acid
–Valproic acid
–Alcohol
–Helothene
2.Trauma
3.Disseminated intravascular coagulation (DIC)
4.Infarction

11. ChronicAcute
Causes: Acute vs. Chronic
•Virus: HAV, HBV, HCV, HDV,
HEV, CMV, EMV, Flabivirus
•Drug: paracetamol, INH,
pyrazinamide, NSAIDs, valproic
acid etc.
•Alcohol
•Infarction/Trauma
•DIC
•Rare: Wilson’s disease,
autoimmune
•Virus: HBV, HCV, HDV
•Drug: methotrexate
•Alcohol
•Fatty liver (NAFLD)
•Biliary stasis: PBC, PSC, cystic
fibrosis
•Genetic: Wilson’s disease,
haemochromatosis, α-1ATD
•Autoimmune
•Venous stasis: Budd-Chiary
syndrome, CHF

12. Virus Characteristics
Virus Hepatitis
A
Hepatitis BHepatitis
C
Hepatitis DHepatitis
E
Nucleic
acid
RNA DNA RNA RNA RNA
Incubation 2-4 weeks4-20 weeks2-26 weeks6-9 weeks3-8 weeks
Spread Fecal-oralBlood Blood Blood Fecal-oral
ChronicityNo Yes Yes Yes
(ē HBV)
No
Vaccine Yes Yes No HBV
vaccine
No

13. Viruses: Photomicrographs
HAV HBV HEV

14. HBsAg
RNA
 antigen
Hepatitis D (Delta)
Virus

15. Clinical Features:
Symptoms
•Asymptomatic
•Prodromal symptoms: weakness, myalgia,
arthralgia, headache
•GI symptoms: anorexia, nausea, vomiting,
lose stool, constipation, abdominal
discomfort/pain
•Yellow urine, yellow eyes (jaundice)
•Features of cholestasis: pruritus, pale stool,
deep jaundice

16. Clinical Features: Signs
•Jaundice
•Tender hepatomegaly
•Ill looking
•Scratch marks for pruritus
•Splenomegaly
•Features of complications: Hepatic
failure, bleeding, infection

17. Pruritus

18. Clinical Features
SGPT/SGOT precedes jaundice

19. Acute Hepatitis:
Gross Appearance of Liver
Haemorrhage
Nacrosis with
furrows

20. Histology
Liver section
under light
microscope

21. Histology
Ballon
degeneration:
Rt. arrow
Councilman
body:
Lt. arrow

22. Outline
•Pathophysiology of acute hepatitis
•Difference with chronic liver disease
•Causes of acute (vs. chronic) hepatitis
•Characteristics of hepatotrophic viruses
•Clinical features
•Complications
•Investigations
•Management
•Fulminant hepatic failure

23. Complications
•Acute liver failure/Fulminant HF (esp. AVH
in pregnancy)
•Hepato-renal syndrome
•Hypoglycaemia
•Cholestatic hepatitis (hepatitis A)
•Aplastic anaemia
•Chronic liver disease and cirrhosis
(hepatitis B and C)
•Relapsing hepatitis

24. Investigations
•Liver function tests:
–SGPT, SGOT
–Serum bilirubin
–Prothrombin time
•Viral markers:
- HBsAg, Anti-HEV IgM, Anti-HAV IgM, Anti-HCV
•USG of liver:
- Hypoechoic liver parenchyma
•Others:
- CBC, Blood sugar, RFT, electrolytes etc.

25. Management
A.General measures:
1. Complete bed rest
2. Nutrition: normal diet
3. Remove offending cause, if any.
B. Medications:
1. Mostly symptomatic
PPI, anti-emetics, laxatives, UDCA, antibiotics
2. Avoid sedatives, narcotics, NSAIDs, diuretics,
alcohol,
elective surgery/trauma
3. Management of complications.

26. Acute Liver Failure

27. Acute Liver Failure
•Synonym: Fulminant hepatic failure.
•Liver failure occurring in the setting of acute
hepatitis.
•Feature of liver failure: encephalopathy,
bleeding manifestation, hypoalbuminaemia.
•Definition: the syndrome occurring within 8
weeks of onset of the precipitating illness, in the
absence of evidence of preexisting liver disease.

28. Classification
Type Time: jaundice
to
encephalopathy
Cerebral
oedema
Common
causes
Hyperacut
e
<7 days Common Viral,
paracetamol
Acute 8-28 days Common Cryptogenic,
drugs
Subacute 29 days-12
months
Uncommo
n
Cryptogenic,
drugs

29. Causes
•Acute viral hepatitis (most common)
•Paracetamol toxicity
•Anti-TB
•Mushroom poisoning (Amanita phalloides)
•Pregnancy,
•Unknown (‘non-A–E viral hepatitis’)

30. Encephalopathy Grade
Clinical
grades
Clinical signs
Grade IPoor concentration, slurred speech, slow
mentation, disordered sleep rhythm.
Grade IIDrowsy but easily rousable, occasional
aggressive behaviour, lethargic, asterixis.
Grade IIIMarked confusion, drowsy, sleepy but
responds to pain and voice, gross
disorientation.
Grade IVUnresponsive to voice, may or may not
respond to painful stimuli, unconscious.

31. Complications
•Encephalopathy and cerebral oedema
•Hypoglycaemia
•Metabolic acidosis
•Infection (bacterial, fungal)
•Renal failure
•Multi-organ failure (hypotension and respiratory
failure).

32. Monitoring
Cardiorespiratory
• Pulse
• Blood pressure
• Central venous pressure
• Respiratory rate
Neurological
• Intracranial pressure monitoring (specialist units)
• Conscious level
Fluid balance
• Hourly output (urine, vomiting, diarrhoea)
• Input: oral, intravenous

33. Investigations
•To determine cause:
Anti-HEV IgM, anti-HBc IgM, anti-HAV IgM,
CMV, HCV, EBV.
S. caeruloplasmin & copper, u. copper, slit-lamp exam.
Autoantibodies: ANA, ASMA, LKM, SLA.
•LFTs: Prothrombin time (2 hourly), ALT, s. bilirubin.
•To assess complication:
RBS (2-hourly), creatinine, electrolytes, ABG, CBC,
platelet
•USG, Doppler study

34. Management
•Admission in HDU/ICU
•Surveillance of complications
•Maintenance of nutrition
•Treatment of complications
•Transplantation.