Effect of adding daclatasvir in sofosbuvir-based therapy in genotype 3 hepatitis C: real-world experience in Pakistan.

OBJECTIVE: To determine real-world effect of adding daclatasvir (DCV) to chronic hepatitis C treatment by comparing sustained viral response of sofosbuvir (SOF)/DCV±ribavirin (RBV) and SOF+RBV combination in patients with genotype 3 hepatitis C. PATIENTS AND METHODS: Patients with chronic hepatitis C, genotype 3, presenting at the DHMC Hepatology Clinic from October 2014 till March 2018 were treated initially with 6 months of SOF/RBV, and once DCV was available, with SOF/DCV±RBV for 3 or 6 months. Negative hepatitis C virus RNA by PCR, sustained viral response 12 weeks after treatment (SVR12), was the primary end point for per-protocol analysis. RESULTS: The mean age of the 440 enrolled patients was 51.04 (±11.9) years, and male to female ratio was 0.97/1 (217/223). Liver cirrhosis was present in 260 (59.1%) patients, and 89 (20.2%) had decompensated liver disease. Treatment-experienced patients were 124 (28.2%). We included 398 (90.4%) patients with completed follow-up in final analysis, excluding either dropped out, failed to complete therapy or died during follow-up. SVR12 was achieved in 366 (91.9%), being significantly lower (P=0.001) in patients with cirrhosis at 89.9% (205/228), and even lower SVR12 (P=0.006) in decompensated cirrhosis at 87.01% (67/77). SVR12 was also inferior (P=0.005) in treatment experienced patients at 85.8% (97/113) than treatment-naive patients at 94.3% (269/285). Among 285 patients treated with SOF/RBV, SVR12 was achieved in 264 (92.6%), which is not significantly different from SVR12 with SOF/DCV±RBV at 90.2% (102/113) (P=0.57). CONCLUSION: In patients with chronic hepatitis C genotype 3, SOF/RBV and SOF/DCV±RBV have similar sustained viral response, and patients with liver cirrhosis and past treatment experience have suboptimal response in Pakistan.