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Background and aim: Telaprevir, a nonstructural (NS)3/4A protease inhibitor, is a direct-acting antiviral drug that inhibits viral replication.Triple therapy with telaprevir, pegylated interferon, and ribavirin is a standard therapeutic regimen for chronic genotype lb hepatitis C virus (HCV) infection and a high viral load.Several factors, including mutations in the NS5A gene, are important predictors of the efficacy of interferon therapy.In this study, we examined the mutational diversity and its impact on the efficacy of triple therapy.Patients: We enrolled patients with chronic genotype lb HCV infection, a high viral load (33 males/17 females;mean age 56.9 years), and on triple therapy.This study was conducted at Kobe University Hospital and at three affiliated hospitals in Hyogo prefecture, Japan, between January 2012 and June 2012.Results: A sustained viral response after 12 weeks (SVR12) was achieved in 37/50 patients (74%).Based on intent-to-treat analysis, SVRi2 was significantly greater in patients with the major allele than in those with the minor allele for the IL28B single nucleotide polymorphism (SNP;86% vs.56%;P < 0.05).The prevalence of the V2334I mutation in NS5A was significantly higher in SVR12 patients, while that of G2356E was significantly higher in non-SVR12 patients (P < 0.05).Mutations in the NS3 region that are thought to confer resistance to telaprevir were detected in 3/27 SVR12 patients (Val36, n =3) and in 5/10 non-SVRl2 patients (Val36, n =4;Thr54, n =1).Conclusion: The IL28B SNP and mutations in the NS5A region were associated with the therapeutic response to triple therapy.Half of non-SVR12 patients had mutations conferring resistance to telaprevir.However,pre-existing mutations in NS3 did not affect the efficacy of triple therapy.