In 2011 TVR + Peg-IFN + RBV triple therapy became available Navitoclax order for use in Japan. Use of this combination reduced the duration of treatment for 48 or 72 weeks to 24 weeks, and provided a marked improvement in therapeutic efficacy, albeit some problems with adverse reactions. In December 2013, national medical insurance coverage approved the use of SMV,[9-11] a second generation protease inhibitor, for the treatment of genotype 1 high viral load infections. The duration

of treatment for SMV + Peg-IFN + RBV triple therapy is 24 weeks, the same as for TVR-based triple therapy. However, once daily dosing for the former, as well as high SVR rates of 80–90% in Japanese clinical trials with treatment naïve subjects (DRAGON,[6] CONCERTO-1,[9] and CONCERTO-4[11]), and similar rates of adverse reactions to the control Peg-IFN + RBV dual therapy group, make SMV + Peg-IFN + RBV triple therapy the present treatment of first choice. There are no clear discontinuation criteria for SMV-based triple therapy, and very

few patients in whom this regimen is contraindicated, so in general the discontinuation criteria for TVR-based triple therapy should be followed. In some patients, however, in whom adverse reactions are a concern, and the risk of carcinogenesis is considered low, it may be possible to await the introduction of the new agents with more favorable safety profiles. In the Japanese CONCERTO −1 trials using SMV-based combination therapy, subanalysis according to IL28B alleles (rs8099917 SNP) yielded an SVR24 rate of 94% (77/82) for the TT allele, and 78% (32/41) Nutlin-3 order for the TG/GG alleles.[9] This represents a relatively high SVR rate for the TG or GG minor alleles achieved with SMV-based combination therapy, unlike Peg-IFN + RBV dual therapy, whose

therapeutic efficacy is strongly affected by IL28B polymorphism (Fig. 4). A similar trend was seen in the CONCERTO-4 trial, with an SVR24 rate of 100% (16/16) for the TT allele, and 75% (6/8) for the TG/GG alleles, although subject numbers were small.[11] In the overseas QUEST-1 and QUEST-2 trials using SMV-based combination therapy, SVR12 rates stratified 上海皓元 for IL28B alleles (rs12979860 SNP) were 97% (72/77) and 96% (72/77) respectively for the CC allele, 76% (114/150) and 80% (114/142) for the CT allele, and 65% (24/37) and 58% (23/40) for the TT allele, showing a similar trend to the Japanese studies (Table 3). SVR24 rates stratified for age in the CONCERTO-1 trial were 87% (20/23) for subjects ≤ 45, 90% (70/78) for those aged 44–64, and 86% (19/22) for those ≥65. No clear differences were seen in SVR rates according to age for those ≤70 years old (Fig. 4). As for fibrosis, QUEST-1 and QUEST-2 examined the relationship between hepatic fibrosis and SVR12 rates, finding SVR12 rates of 83% and 85% respectively for F0-2, 78% and 67% for F3, and 58% and 65% for F4 (Table 3).