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Hepadnavirus (Hepatitis B Virus / HBV)

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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