The aim of the present study was to predict sustained virological response (SVR) to telaprevir with pegylated interferon (PEG-IFN) and ribavirin using viral response within 2 weeks after therapy initiation. Thirty-six patients with genotype 1 hepatitis C virus (HCV) and high viral load were treated by telaprevir-based triple therapy. SVR was achieved in 72% (26/36) of patients. Significant differences between the SVR group and non-SVR group were noted regarding response to prior PEG-IFN plus ribavirin, interleukin (IL)28B polymorphism, amino acid substitution at core 70, cirrhosis, hyaluronic acid level, and HCV-RNA reduction within 2 weeks. Setting 4.56？logIU/mL as the cut-off value for HCV-RNA reduction at 2 weeks, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for predicting SVR were 77%, 86%, 95%, 50%, and 79%, respectively, and for neither the IL28B minor allele nor core 70 mutant were 80%, 71%, 91%, 50%, and 78%, respectively. In conclusion, evaluation of viral reduction at 2 weeks or the combination of IL28B polymorphism and amino acid substitution at core 70 are useful for predicting SVR to telaprevir with PEG-IFN and ribavirin therapy. 1. Introduction To date, although pegylated interferon (PEG-IFN) and ribavirin combination therapy has been standard care for patients with hepatitis C virus (HCV) infection, the sustained virological response (SVR) rate in patients with genotype 1 and high viral load is only approximately 40–50% [1]. Recently, some direct antiviral agents (DAAs) against HCV have been developed. The first-generation nonstructural 3/4A protease inhibitor, telaprevir, became available for clinical use in November 2011 in Japan. Triple therapy with telaprevir, PEG-IFN, and ribavirin has significantly improved SVR rates to around 70% [2]. However, compared with PEG-IFN plus ribavirin therapy, triple therapy can produce some severe adverse reactions, including serious skin disorders, exacerbation of anemia, and renal dysfunction [3–5]. Furthermore, the safety of telaprevir-based triple therapy in elderly or cirrhotic patients has not been established. However, as elderly and/or cirrhotic patients are at high risk of developing hepatocellular carcinoma, antiviral therapy should be commenced as soon as possible for these patients [1]. Therefore, the prediction of efficacy and assessment of tolerability for each individual who might receive telaprevir-based triple therapy are crucial for deciding the optimal treatment strategy. If therapeutic efficacy can be accurately predicted before or
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