USMLE

Hepatitis C Virus (HCV)

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Viruses - RNA Viruses
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Key Points

  • Hepatitis C virus (HCV)
    • Member of Flavivirus family
    • Characteristics
      • Lacks 3’-5’ exonuclease activityno proofreading ability
        • Antigenic variation of HCV envelope proteins (hypervariable region) due to frequent mutation
        • Host antibody production lags behind production of new mutant strains of HCV
    • Transmission
      • Blood (IVDU, post-transfusion)
      • Perinatal transmission is possible
      • Sexual transmission
        • Can occur, but is exceedingly rare (contrast vs. HBV)
      • Carrier state very common
    • Presentation
      • Acute hepatitis
        • Self-limited, asymptomatic or with mild symptoms
        • Usually leads to chronic infection
      • Chronic Hepatitis
        • Long incubation period (occurs over many years)
        • Fever, jaundice, elevated ALT and AST (ALT > AST)
        • Increases risk of cirrhosis or Hepatocellular Carcinoma (HCC)
          • Chronic infection causes regenerative hyperplasia, and increased replication rate and inflammation leads to increased mutation risk
          • As an RNA virus, HCV does not integrate DNA into host cell genome (unlike HBV)
      • Associated with:
        • Essential mixed cryoglobulinemia
        • B-cell non-hodgkin Lymphoma
        • Immune thrombocytopenic purpura (ITP)
        • Autoimmune hemolytic anemia
        • Membranoproliferative GN
          • Also membranous GN (more rare)
        • Leukocytoclastic vasculitis
        • Porphyria cutanea tarda
        • Lichen planus
        • Diabetes mellitus
        • Autoimmune hypothyroidism
    • Diagnosis
      • Liver biopsy
        • Lymphoid aggregates in portal tracts
        • Focal areas of macrovesicular steatosis
        • All viral hepatitis produce a similar histopathological pattern
        • Hepatocyte swelling (necrosis)
          • “Ballooning degeneration”, thought to be caused by ATP depletion and disruption of cytoskeleton
          • Hyperplasia may also occur due to regeneration of tissue (active cell replication) lost to viral damage
        • Monocyte infiltration
          • Occurs due to viral infection and hepatocyte necrosis
        • Councilman bodies
          • Apoptotic bodies form round pink (eosinophilic) bodies known as Councilman bodies
    • Treatment
      • Ribavirin
        • Antimetabolite that inhibits RNA replication via multiple mechanisms
          • inhibits IMP dehydrogenase (depletes GTP)
            • See De Novo Purine Synthesis
          • inhibits RNA polymerase (RNA replication)
          • induces lethal hypermutation
      • Interferon alpha
      • Sofosbuvir
        • Inhibits nonstructural protein 5B (NS5B), an RNA-dependent RNA polymerase needed for HCV replication
      • Protease inhibitors are also used