Hepatitis Part 1

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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
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>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
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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
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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)
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