Retreatment of patients with chronic hepatitis C, subtype 3a, and cirrhosis, who previously failed a regimen containing NS5A inhibitors with sofosbuvir/velpatasvir plus ribavirin for 24 weeks

Background & Aims The use of direct acting antiviral agents (DAAs) in patients with chronic HCV genotype (GT) 3a infection results in sustained virologic response (SVR) rates of 93–98%, but 5–8% of patients experience virologic failure. Methods. We observed 48 patients infected with HCV subtype 3a who failed previous treatment with DAAs, including 43 subjects (89.6%) with liver cirrhosis. Thirty-seven (77%) subjects previously received NS5A inhibitors of the first generation (daclatasvir) and 11 subjects (23%) – of the second generation (velpatasvir). All patients received retreatment with sofosbuvir (SOF)/ velpatasvir (VEL) and ribavirin (RBV) for 24 weeks. We compared SVR₁₂ rates depending on fibrosis stage, presence of NS5A mutation (L31M or A30K and Y93H), and on the generation of previously used NS5A inhibitors. Results. Observed SVR₁₂ rate were: 83,3% (40/48 patients) overall; 100% in patients without cirrhosis (n=5) vs 81,4% (n=35) in those with cirrhosis (n=43) (P=0,01); 86,7% (n=13) with single L31M or A30K(n=15) vs 77,8% (n=21) with Y93H mutation (n=27) (P=0,46), 86,5% (n=32) in patients who previously failed first generation (n=37) vs 72,7% (n=8) in those who failed second generation NS5A inhibitors (n=11) (P=0,35). Conclusions. Retreatment with SOF/VEL+RBV was highly effective and safe in patients with chronic HCV GT3a infection, including those with liver cirrhosis, who previously failed DAA containing NS5A inhibitors. Presence of NS5A RASs L31M, A30K, and Y93H at the baseline, as well as the generation of previously used NS5A inhibitors did not impact SVR₁₂ rates.