0%); and (3) sustained virological response (11.8%) was the worst in patients who possessed both of genotype TG and GG, and Gln70(His70). Two previous studies (PROVE1 in the US, and PROVE2 in Europe) showed that the T12PR12 and T12PR24 group of telaprevir, PEG-IFN, and ribavirin could achieve sustained virological response rates of 35%-60% and 61%-69%, respectively.10, 11 In the present Japanese study, the sustained virological response rates were 45% and 67% in the T12PR12 and T12PR24 group, respectively, as in the two previous studies. There were differences at three points between the present study and two previous studies: (1) PEG-IFN in two previous studies

was used at a fixed dose of PEG-IFNα-2a, but that Kinase Inhibitor Library clinical trial of the present study was a body weight-adjusted dose of PEG-IFNα-2b; (2) The body mass index of our patients (median; 23 kg/m2) was much lower Protein Tyrosine Kinase inhibitor than that of the participants of the previous study

by McHutchison et al.10 (median; >25 kg/m2); and (3) The present study was performed based on Japanese patients infected with HCV-1b, except for only one patient with HCV-1a. Especially in PROVE-1, the viral breakthrough rate was higher in HCV-1a subjects compared to HCV-1b, and one of the reasons might be due to the low genetic barrier to the emergence of the R155K variant in HCV-1a.10, 27 Further studies of a larger number of patients matched for background, including genotype, race, body mass index, treatment regimen, and past history of IFN therapy are required to investigate the rate of the sustained virological response by triple therapy. IL28A,

IL28B, and IL29 (IFN-λ-2, IFN-λ-3, and IFN-λ-1, respectively) are novel IFNs identified recently.28, 29 They are similar this website to type 1 IFNs in terms of biological activities and mechanism of action, in contrast to their differences in structure and genetics.30 The antiviral effects of IFN-λ against hepatitis B virus and HCV have been reported.31 Furthermore, α and λ IFNs act synergistically against HCV.32-34 Recent reports showed that genetic variation near the IL28B gene (rs8099917, rs12979860) are pretreatment predictors of virological response to 48-week PEG-IFN plus ribavirin combination therapy in individuals infected with HCV-1,18-21 and also affect clinical outcome, including spontaneous clearance of HCV.22 At the 2009 meeting of the American Association for the Study of Liver Diseases, Thompson et al.35 reported that genetic variation near the IL28B gene also affected the viral suppression in the first 2 to 4 weeks of PEG-IFN plus ribavirin, and this phenomenon probably explains much of the difference in treatment response rate. The present study is the first to report that genetic variation near the IL28B gene significantly also affect sustained virological response by triple therapy.