A patient with hepatitis C virus (HCV) genotype 1 infection and compensated cirrhosis is started on sofosbuvir/ledipasvir for 12 weeks. Which baseline factor most significantly increases the risk of treatment failure with this regimen?
- A Prior interferon treatment failure
- B Age > 60 years
- C Presence of baseline NS5A resistance-associated substitutions (RAS) with high baseline viral load ✓
- D Female sex
Correct answer: C. Presence of baseline NS5A resistance-associated substitutions (RAS) with high baseline viral load
Explanation
With direct-acting antiviral (DAA) regimens targeting NS5A (like ledipasvir), the presence of pre-existing NS5A resistance-associated substitutions (RAS) combined with high baseline HCV RNA (>6 million IU/mL) increases risk of virologic failure — prompting extension to 24 weeks or addition of ribavirin in cirrhotic patients. Prior interferon failure does not significantly affect DAA response. Age and sex have minimal impact on modern DAA efficacy.
Reference: Harrison's Principles of Internal Medicine, 21st ed.
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Written and medically reviewed by the StethoPrep medical team.