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Viral Hepatitis - MBBS 2nd Year (Pathology)

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Overview

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Comparison Table - The Five Hepatitis Viruses

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1. Hepatitis A Virus (HAV)

• Incubation: 2-6 weeks
• Self-limited; does NOT cause chronic hepatitis
• Does NOT establish a carrier state (viremia is transient)
• Rarely (<0.1%) produces fulminant hepatitis
• Hepatocellular injury is immune-mediated, predominantly by cytotoxic CD8+ T cells (HAV is not directly cytopathic)

• IgM anti-HAV = marker of acute infection; appears at symptom onset, declines in a few months
• IgG anti-HAV = appears during convalescence; persists for years (lifelong immunity)
• Blood not screened (viremia transient)
• Vaccine available since 1995; has reduced HAV rates by >95%

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2. Hepatitis B Virus (HBV)

1. HBcAg (core antigen) - stays in hepatocytes; participates in virion assembly
2. HBeAg (e antigen) - secreted into blood; marker of active replication
3. HBsAg (surface antigen) - envelope glycoprotein; secreted in massive quantities; basis of the vaccine
4. HBx protein - transcriptional transactivator; implicated in hepatocellular carcinoma pathogenesis

• High-prevalence areas: perinatal (accounts for 90% of cases)
• Intermediate prevalence: horizontal transmission in early childhood
• Low-prevalence areas: unprotected sex, IV drug use

1. Acute hepatitis with recovery (most common in adults)
2. Nonprogressive chronic hepatitis
3. Progressive chronic disease → cirrhosis
4. Fulminant hepatitis with massive liver necrosis
5. Asymptomatic "healthy" carrier state

• Neonates: >90% become chronic carriers
• Children: ~30%
• Adults: only 5%-10%

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3. Hepatitis C Virus (HCV)

• A protease (needed for polyprotein processing) - target of direct-acting antivirals
• NS5A (essential for viral assembly)
• RNA polymerase (needed for replication) - target of antivirals

• ~85% of acute infections are asymptomatic and go unrecognized
• Chronic hepatitis develops in 80%-90% (contrast: only 5-10% with HBV)
• Cirrhosis develops in ~20% over 20-30 years

• HCV RNA detectable 1-3 weeks after exposure (before symptoms)
• Anti-HCV appears later; does NOT confer protection (circulating HCV RNA persists in 90% of patients despite antibody)
• Diagnosis of chronic HCV: confirmed by HCV RNA PCR (not just antibody alone)
• Episodic transaminase elevations with intervening normal periods are characteristic

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4. Hepatitis D Virus (HDV)

• Also called delta agent - a defective RNA virus that requires HBV for its life cycle (uses HBsAg as its envelope)
• Circular defective ssRNA; classified in Deltaviridae family
• Affects ~15 million people worldwide (5% of HBV carriers)
• Transmission: parenteral (IV drug use, transfusions)

• HDV RNA in blood and liver at onset
• IgM anti-HDAg = recent HDV exposure
• In chronic superinfection: HBsAg + IgG/IgM anti-HDV persist

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5. Hepatitis E Virus (HEV)

• Enterically transmitted, waterborne infection (like HAV)
• Zoonotic disease - animal reservoirs include monkeys, cats, pigs, dogs
• Incubation: 4-5 weeks
• Epidemics in Asia, Indian subcontinent, sub-Saharan Africa, Mexico
• Accounts for 30%-60% of sporadic acute hepatitis in India

• High mortality in pregnant women - approaching 20% (especially 3rd trimester)
• Usually self-limiting; does NOT cause chronic liver disease in immunocompetent hosts
• Can cause chronic infection in immunocompromised patients only
• No specific antiviral treatment; a vaccine exists (licensed in China but not widely elsewhere)

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Clinicopathologic Syndromes

1. Acute asymptomatic infection with recovery - identified by elevated transaminases or antiviral antibodies incidentally (common with HAV and HBV in children)
2. Acute symptomatic infection with recovery:
   • Incubation → preicteric phase (fever, malaise, nausea, RUQ pain) → icteric phase (jaundice, dark urine, pale stools) → convalescence
   • Peak infectivity: last asymptomatic days of incubation + early symptomatic days
3. Acute liver failure (fulminant hepatitis):
   • Viral hepatitis = ~10% of cases of acute hepatic failure
   • HAV = most common cause worldwide; HBV more common in Asia/Mediterranean
   • Defined by massive hepatic necrosis with hepatic encephalopathy
4. Chronic hepatitis: hepatic disease >6 months. Can lead to:
   • Cirrhosis
   • Portal hypertension
   • Hepatocellular carcinoma (especially with HBV and HCV)
   • Extrahepatic manifestations: vasculitis, glomerulonephritis (immune complex disease), cryoglobulinemia (~35% of chronic HCV)
5. Carrier state: Individual harbors and can transmit virus without symptoms. HBV acquired in early life (endemic areas): carrier state in >90%.

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Morphology (Pathology HIGH-YIELD)

Acute Viral Hepatitis

• Liver may be normal, enlarged (due to inflammation), or shrunken (massive necrosis)
• Microscopically:
  • Portal and lobular inflammatory infiltrate: predominantly lymphocytes, plasma cells, eosinophils
  • Hepatocyte injury - necrosis or apoptosis
  • Councilman bodies / acidophilic bodies - apoptotic hepatocytes (small, densely eosinophilic, often extruded from the plate)
  • Ballooning degeneration - swelling of hepatocytes due to hydropic change
  • Confluent necrosis → bridging necrosis (connecting portal-portal or portal-central veins) in severe cases → panlobular (panacinar) necrosis in fulminant disease

Chronic Viral Hepatitis

• Defining histologic feature: Dense portal lymphocytic or lymphoplasmacytic inflammation with fibrosis
• Interface activity (piecemeal necrosis): inflammatory cells crossing the limiting plate, injuring periportal hepatocytes
• Fibrosis progression: portal/periportal fibrosis → portal-portal bridging fibrosis → cirrhosis

Virus-Specific Histologic Clues:

• "Ground-glass" hepatocytes - pale, finely granular eosinophilic cytoplasm due to HBsAg accumulation in ER - DIAGNOSTIC hallmark of chronic HBV

• Large lymphoid aggregates in portal tracts (lymphoid follicles)
• Fatty change (steatosis) in scattered hepatocytes
• Bile duct injury in some cases (mimics primary biliary cholangitis)

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Summary - High-Yield Memory Points for Exams

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