Hepatitis C Virus (HCV)

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Viruses - RNA Viruses

Key Points

Hepatitis C virus (HCV)
- Member of Flavivirus family
- Characteristics
  - Lacks 3’-5’ exonuclease activity → no 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