Any generalization of the results should await confirmation by studies of patients of other races to explore the relationship between genetic variation near the IL28B gene and the response to triple therapy. The present study indicated that the use of the combination of aa learn more substitution of the core region and genetic variation near the IL28B gene had
high sensitivity, specificity, PPV, and NPV for prediction of sustained virological response. The efficacy of triple therapy was high in the patients with TT, irrespective of substitution of core aa 70. In the patients having non-TT, those of Arg70 gained high sustained virological response, and sustained virological response was the worst in patients who possessed both non-TT, and Gln70(His70). Along with a high sustained virological response, combined PEG-IFN and ribavirin are accompanied by severe side effects and entail high costs. Hence, the patients who do not achieve sustained virological response need to be identified as early as possible, in order to free them of unnecessary side effects and high costs. The present study is the first to report that the combination of aa substitution of the core region and genetic variation near the IL28B gene are very useful as pretreatment predictors of sustained virological response by triple GPCR Compound Library chemical structure therapy, and further studies based on a larger number of patients are necessary to investigate the present
Cyclin-dependent kinase 3 results. Other limitations of the present study were that aa substitutions in areas other than the core region and NS5A-ISDR of the HCV genome, such as the interferon/ribavirin resistance determining region (IRRDR),36 were not examined. Furthermore, HCV
mutants with aa conversions for resistance to telaprevir during triple therapy, such as the 156S mutation,37 were also not investigated. In this regard, telaprevir-resistant HCV mutants were reported to be susceptible to IFN in both in vivo and in vitro studies.38, 39 Thus, viral factors before and during triple therapy should be investigated in future studies and identification of these factors should facilitate the development of more effective therapeutic regimens. In conclusion, triple therapy with telaprevir, PEG-IFN, and ribavirin in Japanese patients infected with HCV-1 and high viral load achieved high sustained virological response rates. Furthermore, the aa substitution pattern of the core region and genetic variation near the IL28B gene seem to affect treatment efficacy. Further large-scale prospective studies are necessary to investigate whether the present results relate to the efficacy of triple therapy and further understanding of the complex interaction between virus- and host-related factors should facilitate the development of more effective therapeutic regimens. This study was supported in part by a Grant-in-Aid from the Ministry of Health, Labor and Welfare, Japan.
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