Hepadnavirus

Key Points

• Hepadnavirus
  • Key Viruses
    • Hepatitis B virus (HBV)
  • Characteristics
    • DNA virus
      • Replicates in nucleus
      • Replicates using reverse transcriptase
        • Partially double-standed DNA → polymerase completes dsDNA → transcription into RNA template (used to make viral proteins) → reverse transcription into dsDNA progeny
      • Nucleocapsid core contains hepatitis B core antigen, HBcAg
    • Enveloped
      • Lipoprotein envelope surrounds nucleocapsid core
      • Contains hepatitis B surface antigen, HBsAg and envelope antigen, HBeAg
    • Circular chromosome
  • Transmission
    • Many routes
      • Blood (transfusion, IVDU, shared needles)
      • Sexual contact
      • Perinatal
      • Transplant
  • Pathogenesis
    • Migrates to liver and replicates in hepatocytes
    • Causes immune-mediated damage by CD8+ T-cells and NK cells
      • No direct cytotoxic effect of virus
      • CD8+ T-cells recognize HBsAg and HBcAg presented on MHCI of hepatocytes
  • Presentation
    • Acute hepatitis
      • Fever, jaundice, elevated ALT and AST (ALT > AST)
      • Most cases are acute and will undergo complete resolution (>95%)
    • Chronic hepatitis occurs in 4-5% of patients
      • Long incubation period (months)
      • May progress to Cirrhosis or Hepatocellular Carcinoma (HCC)
        • Integration of HBV DNA into hepatocyte genome may cause inactivation of tumor suppressor genes
          • HBV has a higher risk of HCC than HCV
        • Chronic infection causes regenerative hyperplasia, and increased replication rate and inflammation leads to increased mutation risk
    • Fulminant hepatitis with necrosis happens in <1% of patients
      • More common in neonates; worse prognosis
    • Associated conditions
      • Polyarteritis nodosa
      • Membranous nephropathy
        • Also membranoproliferative glomerulonephritis (more rare)
      • Aplastic anemia (rare)
  • Diagnosis
    • Biopsy
      • Granular eosinophilic “ground-glass” appearance
        • Hepatocyte cytoplasm is filled with HBsAg (surface antigen), forming dull homogeneous granular eosinophilic inclusions.
      • All viral hepatitis produce a similar histopathological pattern
        • Panlobular infiltrates, ballooning hepatocytes, hepatocyte necrosis, and hepatocyte apoptosis
        • Apoptotic bodies form round pink (eosinophilic) bodies known as Councilman bodies
    • Serologic studies
      • HBsAg
        • Antigen found on surface of HBV
        • Active infection
        • First marker detectable in serum after inoculation
      • Anti-HBs
        • Antibody to HBsAg
        • Immunity to HBV (prior infection/recovery or vaccination)
      • HBcAg
        • Antigen found on nucleocapsid core of HBV
        • Not detectable in serum (low clinical utility)
          • Usually sequestered/held inside the envelope
          • Found in hepatocytes
      • Anti-HBc
        • Antibody to HBcAg
        • IgM → acute (recent) infection
          • Present in window period
            • When HBsAg has been cleared, but anti-HBs is not yet detectable
            • May be only serologic test suggesting + infection
        • IgG → long past exposure (recovery)
          • Rarely may also be an indicator of chronic infection
      • HBeAg
        • Antigen found on envelope of HBV; secreted by infected hepatocytes into circulation
          • Not part of mature HBV virion
        • High infectivity
          • Suggests active replication
      • Anti-HbeAg
        • Antibody to HBeAg
        • Suggests low transmissibility
  • Treatment
    • Mainly supportive care for acute hepatitis; most cases resolve spontaneously
      • Passive immunization (anti-Hbs IG) and vaccination of close contacts
    • Treatment of chronic hepatitis B is an evolving field of study
      • Entecavir and tenofovir typically used first-line
        • Pegylated interferon (PegIFN) is second-line
  • Vaccination
    • Contains HBsAg
      • Stimulates production of anti-HBsAg in host
    • Serologies positive for Anti-HBs, negative for everything else after successful vaccination