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 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
- Lacks 3’-5’ exonuclease activity → no proofreading ability
- 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
- Acute hepatitis
- 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
- Liver biopsy
- 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
- inhibits IMP dehydrogenase (depletes GTP)
- Antimetabolite that inhibits RNA replication via multiple mechanisms
- Interferon alpha
- Sofosbuvir
- Inhibits nonstructural protein 5B (NS5B), an RNA-dependent RNA polymerase needed for HCV replication
- Protease inhibitors are also used
- Ribavirin