hepatitis. definition & causative organisms infections of the liver caused by a group of viruses...
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HEPATITIS
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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
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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)%
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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
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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
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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 +
.
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Pathogenesis
• Immunologic reaction to virally infected hepatocytes.
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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
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Serological markers of acute hepatitis A
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Morphology of acute hepatitis
• Gross• Early stage• Enlarged tender liver• Later stage• smaller greenish focal depressions due to
areas of collapse may be seen
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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
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Morphology of acute hepatitis
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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
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Acute yellow atrophy
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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
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• 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
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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)