Hepatitis C Virus

Snapshot

• A 35-year-old man presents to his primary care physician for worsening abdominal pain and “yellowing” of the skin. He reports that his symptoms began a few weeks ago and is associated with pale stools and dark urine. He denies any sick contacts and cannot identify a likely cause of his symptoms. He endorses to using opiates use via injection and is sexually active with multiple men and inconsistently using condoms. On physical exam, scleral icterus is appreciated in an uncomfortable appearing man. Abdominal exam is notable for tenderness to palpation in the right upper quadrant with mild hepatomegaly. Laboratory testing is notable for elevated aspartate and alanine aminotransferases and HCV RNA and anti-HCV antibody levels.

Introduction

• Classification
  • a Hepacivirus virus from the Flaviviridae family
    • a linear, positive-sense single-stranded RNA with an icosahedral capsid
• Epidemiology
  • risk factors
    • intravenous drug use
    • healthcare-related exposure (e.g., needlestick injuries and blood transfusions)
    • HIV infection
    • men who have sex with men
    • incarceration
• Pathogenesis
  • not fully understood
  • HCV does not have a 3′-5′ exonuclease activity
    • this impairs genomic proofreading, leading to the production of new mutant strains
• Associated conditions
  • membranoproliferative and membranous nephropathy
  • hepatocellular carcinoma/hepatoma
  • essential mixed cryoglobulinemia 
  • B-cell non-Hodgkin lymphoma
  • leukocytoclastic vasculitis
  • autoimmune hemolytic anemia
  • sporadic porphyria cutanea tarda
  • lichen planus
  • autoimmune hypothyroidism
• Prognosis
• most cases result in chronic hepatitis C virus (HCV) infection

Presentation

• Symptoms
  • typically asymptomatic
  • fatigue
  • myalgia
  • right upper quadrant abdominal pain
• Physical exam
  • jaundice
  • dark urine
• clay colored stools

Studies

• Serologic studies
  • anti-HCV antibodies and HCV RNA
    • initial test when there is a concern for an acute HCV infection
• elevated aminotransferase levels

Differential

• Hepatitis A infection
  • differentiating factor
    • presence of anti-hepatitis A antibodies in serological testing
• Hepatitis B infection
  • differentiating factor
• presence of anti-hepatitis B antibodies in serological testing

Treatment

• Medical
  • hepatitis C therapy
    • indication
      • first-line treatment for acute and chronic hepatitis C infection
    • medical regimens
      • viral phosphoprotein (NS5A) inhibitor (“-asvir”)
        • e.g., ledipasvir
      • HCV RNA-dependent RNA polymerase (NS5B) inhibitor (“-buvir”)
        • e.g., sofosbuvir 
      • guanine nucleotide synthesis inhibitor 
        • e.g., ribavirin
      • HCV protease (NS3/4A) inhibitor (“-previr”)
• e.g., simeprevir

Complications

• Advanced hepatic fibrosis
• Cirrhosis
• Hepatic decompensation
• Hepatocellular carcinoma