Hepatitis

Viral Hepatitis
Hepatotropic viruses HAV:: faeco-oral route HBV: parenterally transmitted disease (chronic) HCV: transfusion related HDV: superinfection with HBV HEV: water-borne

HGV: parenterally transmitted

All are RNA viruses except HBV ---DNA virus

Hepatitis A
20-25% clinical hepatitis 15-45 days incubation Epidemic and sporadic Faeco-oral route Overcrowding, poor hygiene and sanitation 5-14 years Pathogenesis: IgM anti-HAV antibody:: appears in serum at the onset of acute hepatitis A IgG anti-HAV antibody:: detected in serum after IgM antibody----gives lifelong protective immunity against reinfection with HAV

Hepatitis B
30-180 days incubation Pathogenesis: Hepatocellular damage HBs Ag: appears early in blood after 6 weeks of infection---disappears in 36 months---persistence indicates carrier state Anti-HBs: appears 3 months after onset---protective immunity HBeAg: 3-6 weeks during acute attack----persistent beyond 10 weeks---

chronic liver disease and carrier stste

Anti-HBe: appears after disapperance of HBeAg---seroconversion indicates resolution of infection

Hepatitis B
Pathogenesis: HBcAg: cannot be detected in blood----nuclei of hepatocytes in carrier state---only in chronic state Anti-HBc: pre-icteric stage----IgM anti-HBc ----4-6 months followed by IgG anti-HBc Detection of high titre of IgM anti-HBc-----acute HBV infection----elevated IgG anti-HBc----past HBV infection

HBV-DNA: sensitive index---pre-symptomatic phase and early acute stage

Hepatitis D
Concomitant HBV Simultaneous (co-infection):: mild to fulminant HDV infects a chronic carrier (superinfection):: severe and fulminant acute attacks, progression of carrier state----chronic delta/ cirrhosis High risk individuals:: IV drug abusers, homosexuals, transfusion recipients and health care workers Pathogenesis:

Cytopathic effect on hepatocytes

Hepatitis C
NANB hepatitis Blood transfusions, blood products, haemodialysis, iv drug abuse, accidental cuts, needle pricks in health workers 90% post transfusion hepatitis 1-2% volunteer blood donors and upto 5% of professional blood donors are carriers of HCV 20-90 days incubation

HCV----higher rates of progression to chronic hepatitis than HBV

Cirrhosis after 5-10 years Progression to hepatocellular carcinoma

Hepatitis C
Viral and serologic markers Anti-HCV:: third>second >first generation (1-3 months) HCV-RNA:: detected within few days----appear before anti-HCV Pathogenesis Injury to hepatocytes

Hepatitis E and G
Hepatitis E Enterically transmitted Young and middle aged Contamination of water supplies---monsoon/ flooding High mortality in pregnant women Chronic liver disease Hepatitis G Blood borne, acute and chronic Blood donors Transmitted by blood transfusion

Clinicopathologic spectrum
Carrier state Asymptomatic infection Acute hepatitis Chronic hepatitis Fulminant hepatitis (submassive massive necrosis)

Carrier state
Asymptomatic individual---no disease---harbouring infection with hepatotropic virus---capable of transmiting Asymptomatic healthy carrier:: does not suffer from ill-effects of virus infection Asymptomatic carrier with chronic disease:: capable of transmiting Hepatitis A and E---no carrier state Hepatitis B:: largest carrier---early age at infection and impaired immunity

2-3%---asymptomatic carrier of HCV

Healthy HBV carriers:: fine granular, eosinophilic cytoplasm---HBsAg Asymptomatic carrier with chronic disease:: cirrhosis

Asymptomatic infection
Raised serum transaminases Detection of presence of antibodies

Acute hepatitis
Incubation period:: asymptomatic, infectivity highest---last days

Acute hepatitis
Pre-icteric phase Anorexia Nausea, vomiting Fatigue, Malaise Athralgia Headache Low grade fever, jaundice Elevation of transaminases

Acute hepatitis
Icteric phase 1-4 weeks Dark coloured urine---bilirubinuria Pruritis---elevated serum bile acids Loss of weight Abdominal discomfort---enlarged, tender liver Elevated serum bilirubin, transminases, ALP

Acute hepatitis
Post-icteric phase 2-12 weeks 1% cases--- fulminant hepatitis 5-10% cases---chronic hepatitis

Acute hepatitis: Pathological changes

Grossly: liver enlarged, greenish and soft Morphologically: Hepatocellular injury:: 3 centrilobular zones Ballooning degeneration:: swollen hepatocytes, granular cytoplasm which condense around nucleus Councilman body:: acidophilic degeneration, small nucleus, necrotic mass Dropout necrosis:: isolated small clusters of hepatocytes undergoing lysis

Bridging necrosis:: necrosis linking portal tracts to central hepatic veins,

one central hepatic vein to another or one portal tract to another

Ballooning degeneration

Acute hepatitis: Pathological changes

Inflammatory infiltrate:: mononuclear cells in portal tracts---permeate to lobule Kupffer cells hyperplasia:: phagocytosed cellular debris, bilr pigments and lipofuscin granules Cholestasis:: intracytoplasmic bile pigment granules Regeneration:: lobular disarray, surviving adjacent hepatocytes---regeneration and hyperplasia----distortion of lobular architecture

Chronic hepatitis
Continuing or relapsing for more than 6 months Combined infection Non-viral causes: chronic alcoholism, drug-induced injury, autoimmune diseases Chronic persistent hepatitis Chronic active (aggressive) hepatitis Chronic lobular hepatitis

HCV:: 40-60% cases

HBV:: 90% HDV superinfection on HBV carrier state:: 10-40% cases

Chronic hepatitis: Pathological changes

Piecemal necrosis periportal destruction of hepatocytes

Necrosed hepatocytes Interface hepatitis:: expanded portal tract by infiltration of lymphocytes, plasma cells, macrophages Expanded portal tracts:: proliferating ducts Portal tract lesions

Inflammatory cell infiltration by lymphocytes, plasma cells, macrophages

Proliferated bile ductules in expanded portals

Chronic hepatitis: Pathological changes

Intralobular lesions Focal areas of necrosis and inflammation Scattered acidophilic bodies in lobule Kupffer cell hyperplasia Bridging necrosis Bridging fibrosis Periportal fibrosis Postnecrotic cirrhosis

Fulminant hepatitis
Submassive necrosis:: 3 months Massive necrosis:: liver failure rapid 2-3 weeks Acute viral hepatitis:: HBV, HCV < combined HBV-HDV and rarely from HAV; HEV infection is serioud complication in pregnant women Non-viral causes:: drug toxicity (NSAIDs, acetamoniphen, isoniazid), poisonings, hypoxic injury Pathologic changes

Grossly:: liver small and shrunken, capsule is loose and wrinkled, muddyred and yellow necrosis

Fulminant hepatitis
Pathologic changes Hitologicaly Submassive necrosis:: zone 2 and 3 hepatocytes are wiped out---- collapsed reticulin framework Massive necrosis:: loss of hepatic parenchyma, collapsed and condensed reticulin framework and portal tracts with proliferated bile ductules plugged with bile