2 Definition & causative organisms Infections of the liver caused by a group of viruses having an affinity for the liverInfection of the hepatocytes produces necrosis and inflammation of the liverHepatitis virus A,B,C,D,E (G -no acute orchronic illness)…..EBV,CMV, yellow fever, HSV etc.Part of systemic infection
3 Epidimiology >500 million people infected >350 million chronic carriers of HBV200 million infected with HCVHighest HBV carrier rate in Africa, Asia,W PacificCarrier rates 0.3 (US)-20(SE Asia)%
4 Clinico pathological outcomes of hepatitis Acute asymptomatic infection with recovery: serologic evidence onlyAcute symptomatic hepatitis with recovery: anicteric or ictericChronic hepatitis: without or with progression to cirrhosisFulminant hepatitis: with massive to submassive hepatic necrosisDiagnosis of aetiology by serology,history etc
5 Hepatitis virus A,E : Oro fecal transmission Acute phase and fulminant hepatitisNo chronic phaseB,C,D: parenteral transmissionAcute, chronic, carrier phasePredisposes to HCC
6 Hepatitis A Hepatovirus RNA virus Replication in hepatocyte (few in enterocyte)Oro fecal transmission,2-6 wks incubationNo carrier state or chronic courseIg G Anti HAV + → immunityFulminant liver failure rare %Worse outcome if superimposed on chronic hepatitis C,D or alcoholicVaccine +.
7 PathogenesisImmunologic 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
10 Morphology of acute hepatitis GrossEarly stageEnlarged tender liverLater stagesmaller greenish focal depressions due to areas of collapse may be seen
11 Microscopy of acute hepatitis Ballooning degenerationApoptosis (councilman bodies),Necrosis > zone 3 spotty,bridging,panacinarInflammatory infiltratePeriportal,perihepatocyticInterface hepatitisCholestasisHealing with mitotic activity in hepatocytesLobular disarrayhypertrophy and pigment in kupffer cells
15 Hepatitis B Hepadnaviridae, complete virion (Dane particle) Parenteral transmission IV ,blood ,body fluids, saliva, breast milk, semen, transplacental.4-26 weeks incubation periodHBV vaccination recombinant HbsAg or its immunogenic epitopes, lifelong immunityImmunization 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 polymeraseHBx 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 ICytotoxic T lymphocytes directed against multiple HBV epitopes kill infected hepatocytesAntiviral Antibodies appear → infectivity ends, hepatitis endsReplication continues → carrier with chronic hepatitisIntegrative phase: Integrated into the DNA (chronic hepatitis, HCC)