Morphology: Enveloped, single-stranded positive-sense RNA virus. Family Flaviviridae, genus Hepacivirus. Six major genotypes (1–6) + numerous subtypes. Hepatocyte tropism; high mutation rate; quasi-species within infected hosts.
Typical drugs
- #1Sofosbuvir / Velpatasvir— **Pangenotypic — covers all 6 genotypes.** 400/100 mg PO daily × 12 weeks → cure (SVR12) >95%.
- #2Ribavirin— **Adjunct only — decompensated cirrhosis (Child-Pugh B/C)** with DAA. Not as monotherapy.
Empiric therapy when resistant
DAA failure → resistance testing + retreatment with different DAA class combo (e.g., sofosbuvir + velpatasvir + voxilaprevir — "Vosevi"). ID consult.
Resistance mechanisms
altered-target
NS5A RAS (Y93H, L31M, etc.)
Example: Resistance-associated substitutions. Pre-treatment testing not routinely required for first-line pangenotypic DAAs but considered in treatment-experienced patients.
Resistance notes
Pretreatment NS5A RAS uncommon; emerges with DAA failure (resistance to that class often). Pangenotypic DAAs simplify decisions.
Pearls
HCV is curable with 12-week PO DAA in the modern era — >95% SVR12 (sustained virologic response = cure). Universal screening recommended for all adults ≥18 once + pregnant women each pregnancy (USPSTF 2020). Treat everyone with viremia regardless of fibrosis stage (AASLD 2024). Cirrhosis + cure still need HCC screening q6mo for life (cure removes virus, not cumulative liver damage). HBV reactivation can occur during DAA therapy — screen anti-HBc + HBsAg before tx; treat HBV if positive or monitor q4 weeks. HIV co-infection: cure with DAA + ART (drug interactions with sofosbuvir + ritonavir, atazanavir manageable). Pregnant women: defer treatment to postpartum unless severe disease (DAAs Category B but limited data). Glecaprevir-pibrentasvir (Mavyret) is alternative 8-week pangenotypic option for treatment-naïve no-cirrhosis — shorter course.
References
- AASLD / IDSA HCV Practice Guidance (2024)
- USPSTF HCV Screening (2020)