hepatitis n.
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HEPATITIS
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  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 ----0.1% • 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. 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 Microscopy of acute hepatitis

  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

  17. 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)