Abstract: Objective The aim of this study was to investigate the preliminary efficacy of asunaprevir (ASV) and daclatasvirin (DCV) combination therapy in patients with chronic hepatitis C and hepatitis C liver cirrhosis and the resistance mutations and quasispecies changes. Methods 27 patients with CHC and 13 with hepatitis C-induced liver cirrhosis were recruited in this study, and all patients received ASV and DCV combination therapy for 24 weeks. All the patients were followed-up for 12 weeks. Serum HCV gene regions, including core, E1, E2, NS2, NS3, NS4, NS5A and NS5B were sequenced by using second-generation sequencing and the difference of resistance mutations, HCV quasispecies and Tajima test were analyzed. Results At the end of 12-week follow-up, the sustained virological response was achieved in 38 patients (95.0%), and one patient had Y93H and another one had L31V+Y93H NS5A resistance-associated mutations (RAVs) in the two failed patients; during the period of treatment,7 patients (17.5%) had abnormal laboratory examinations, including serum alanine aminotransferase or uric acide elevation or platelet counts or hemoglobin decrease; in a recurrent patient, L31V+Y93H RAVs was found at baseline and recurrent blood samples, however, the percentage of L31V+Y93H RAVs in recurrent sample was significantly higher than that at baseline; the HCV quasispecies complexity (Sn: 0.91±0.02 vs. 0.40±0.07, t=19.127, P<0.001) and diversity (d:17.70±6.63 vs. 1.65±0.36, t=6.75, P<0.001; dN: 3.55±2.18 vs. 1.37±0.41, t=2.801, P=0.026; dS:48.11±10.06 vs. 2.06±0.90, t=13.598, P<0.001, respectively) in recurrent sample were significantly decreased as compared to those at baseline; in addition, the Result of Tajima test showed that the D<0 in amplified HCV regions from recurrent sample, and the D value was significantly lower in recurrent sample (1.84±1.20 vs.-2.30±0.18,t=10.352, P<0.001). Conclusion Excellent clinical efficacy and safety were observed in our series of patients with CHC or hepatitis C liver cirrhosis with HCV 1b genotype infection, which warrants further and long-term investigation.

Key words: Liver cirrhosis, Hepatitis C, Asunaprevir, Daclatasvirin, Therapy, Quasispecies