HEPATITIS 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 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)% 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 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 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 + . Pathogenesis • Immunologic reaction to virally infected hepatocytes. 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 Serological markers of acute hepatitis A Morphology of acute hepatitis • • • • • Gross Early stage Enlarged tender liver Later stage smaller greenish focal depressions due to areas of collapse may be seen 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 Morphology of acute hepatitis 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 Acute yellow atrophy 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 • 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 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)