In 2011 TVR + Peg-IFN + RBV triple therapy became available Bortezomib solubility dmso 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) learn more 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 MCE 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).