54%, P=0.2). Again, IP-10 significantly augmented the prediction Brefeldin A ARFs of SVR among genotype 1 infected for all three IL28B SNPs with the exception of G allele carriage at rs8099917 (Figure 5). In patients with baseline IP-10 below 150 pg/mL who were homozygous for favorable SNP genotypes, SVR was achieved in 85%, 75%, and 75% for rs12979860 CC, rs12980275 AA, and rs8099917 TT, respectively. Notably, achieving RVR was slightly more predictive of achieving SVR (91%; Table 3) than combinations of IL28B and baseline IP-10. This remained the case even when the analysis was restricted to the genotype 1 infected patients who had no dose reductions, i.e. per-protocol analysis (92% vs. 83% for RVR and rs12979860 CC and baseline IP-10 below 150 pg/mL respectively; n=126).

In contrast to genotype 1, neither IL28B genotype distribution nor baseline IP-10 levels predicted SVR among the 71 HCV genotype 2/3 infected patients. Figure 5 SVR rates in HCV genotype 1 according to IL28B variants and baseline IP-10. Table 3 Sensitivity, specificity, positive and negative predictive values of the likelihood achieving SVR among patients infected with HCV genotype 1 (n=170). In multivariate analyses, both IP-10 and C genotype at rs12979860 were independent predictors of the first phase decline in HCV RNA (P=0.009 and P<0.0001 respectively) as well as RVR (P=0.048 and P=0.016 respectively), and RVR was in turn the only independent predictor of SVR (P=0.001). RVR remained the only predictor of SVR when the analysis was restricted to the fully compliant patients (P=0.

005) reiterating the importance of monitoring on-treatment response. Discussion In spite of the pending introduction of direct antiviral agents (DAA) in routine clinical practice, interferon-�� and ribavirin are likely to retain pivotal roles in the management of chronic HCV infection, and thus predicting responsiveness to interferon/ribavirin-based therapies will remain important. In this setting, the main finding in the present study was that pretreatment plasma levels of IP-10 increased the level of prediction of the first phase decline in HCV RNA among patients carrying IL28B SNP variants, which translated into improved prediction of RVR and SVR. Considering the high SVR rates among HCV genotype 1 infected homozygous carriers of CC at rs12979860, AA at rs12980275, or TT at rs8099917 with baseline IP-10 levels below 150 pg/mL (85%, 76%, and 75% respectively), these patients, Carfilzomib although few in number, should be encouraged to initiate therapy and may be candidates for shortened duration of therapy in line with current treatment guidelines considering the high likelihood of achieving RVR [24], [25].