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

hepatitisIntegrative phase: Integrated into the DNA (chronic

hepatitis, HCC)