1. HEPATITIS

2. Definition & causative organisms
Infections of the liver caused by a group of viruses having an affinity for the liver
Infection of the hepatocytes produces necrosis and inflammation of the liver
Hepatitis virus A,B,C,D,E (G -no acute or
chronic illness)…..
EBV,CMV, yellow fever, HSV etc.
Part of systemic infection

3. Epidimiology >500 million people infected
>350 million chronic carriers of HBV
200 million infected with HCV
Highest HBV carrier rate in Africa, Asia,W Pacific
Carrier rates 0.3 (US)-20(SE Asia)%

4. Clinico pathological outcomes of hepatitis
Acute asymptomatic infection with recovery: serologic evidence only
Acute symptomatic hepatitis with recovery: anicteric or icteric
Chronic hepatitis: without or with progression to cirrhosis
Fulminant hepatitis: with massive to submassive hepatic necrosis
Diagnosis of aetiology by serology,history etc

5. Hepatitis virus A,E : Oro fecal transmission
Acute phase and fulminant hepatitis
No chronic phase
B,C,D: parenteral transmission
Acute, chronic, carrier phase
Predisposes to HCC

6. Hepatitis A Hepatovirus RNA virus
Replication in hepatocyte (few in enterocyte)
Oro fecal transmission,2-6 wks incubation
No carrier state or chronic course
Ig G Anti HAV + → immunity
Fulminant liver failure rare %
Worse outcome if superimposed on chronic hepatitis C,D or alcoholic
Vaccine + .

7. Pathogenesis
Immunologic reaction to virally infected hepatocytes.

8. Biochemical changes in viral hepatitis
Necrosis of hepatocytes, release of enzymes ALT ↑↑, AST ↑↑
S. biliribin ↑↑ 10 days-1 month –conjugated (disruption of bile canaliculi & interference with excertion)
Alk phosphatase ↑ (interference with excertion)
↓ protein production ↑ prothrombin time

9. Serological markers of acute hepatitis A

10. Morphology of acute hepatitis
Gross
Early stage
Enlarged tender liver
Later stage
smaller greenish focal depressions due to areas of collapse may be seen

11. Microscopy of acute hepatitis
Ballooning degeneration
Apoptosis (councilman bodies),
Necrosis > zone 3 spotty,bridging,panacinar
Inflammatory infiltrate
Periportal,perihepatocytic
Interface hepatitis
Cholestasis
Healing with mitotic activity in hepatocytes
Lobular disarray
hypertrophy and pigment in kupffer cells

12. Morphology of acute hepatitis

13. Fulminant hepatitis Entire/part of liver involved
Liver shrinks,limp,wrinkled capsule
Microscopy: destruction of hepatocytes in contiguous lobules, collapsed reticulin framework,preserved portal tracts
Regeneration +/- fibrosis
C/F jaundice,encephalopathy etc

14. Acute yellow atrophy

15. Hepatitis B Hepadnaviridae, complete virion (Dane particle)
Parenteral transmission IV ,blood ,
body fluids, saliva, breast milk, semen, transplacental.
4-26 weeks incubation period
HBV vaccination recombinant HbsAg or its immunogenic epitopes, lifelong immunity
Immunization in infancy

16. DNA partly double stranded
Core protein (HBcAg)
Lipo protein coat bearing Envelope glycoprotein (HBsAg) (Australia antigen Baruch S Blumberg in the serum of an aborigine)
DNA polymerase
HBx necessary for virus replication

18. Pathogenesis of hepatitis B
Proliferative phase: Episomal form produces complete viral particles (Infectivity)
Target viral antigens(HBsAg,HBcAg )expressed on the surface in association with HLA class I
Cytotoxic T lymphocytes directed against multiple HBV epitopes kill infected hepatocytes
Antiviral Antibodies appear → infectivity ends, hepatitis ends
Replication continues → carrier with chronic hepatitis
Integrative phase: Integrated into the DNA (chronic hepatitis, HCC)