05). Similar results were observed in multivariate analyses (Table 3), with a significant effect of rs8099917 in the whole sample (odds ratio [OR] for having necroinflammatory activity in GT/GG versus TT subjects = 0.719, 95% confidence interval [CI] 0.528-0.979, P = 0.04). This protective effect was again stronger in patients CDK inhibitor infected with non-1 genotypes with an OR at 0.482 (95% CI 0.300-0.776, P = 0.003). Similar results, although less significant, were observed for rs12979860: here, the proportion of patients with HCV non-1 genotypes presenting with necroinflammatory activity was 0.58 in CT/TT subjects as compared to 0.67 in CC subjects (P = 0.05;
Table S2). For rs8099917 the proportion of patients with fibrosis MK 2206 ≥F2 was 0.48 in GT/GG and 0.54 in TT patients (P = 0.03; Table S2). Accordingly, the proportions of rapid progressors (FPR ≥0.077) were 0.46 and 0.54 in GT/GG and TT patients, respectively (P = 0.004; Table S2). Important differences were noted when patients were stratified according to viral genotypes (Fig. 1C,D). The associations between rs8099917 and both fibrosis and FPR were stronger in patients infected with non-1 genotypes, e.g., the proportions of those patients with fibrosis ≥F2 were 0.48 and 0.61 in GT/GG and TT patients, respectively (P = 0.001; Table S2), and the proportions
of rapid progressors were 0.52 and 0.62, respectively (P = 0.02). In multivariate analyses, the associations were also highly significant (Tables 4, 5). For GT/GG versus TT patients infected with non-1 genotypes, the OR of developing a fibrosis ≥F2 was 0.431 (95% CI 0.265-0.703, P = 0.001), and the OR of being a rapid progressor was 0.564 (95% CI 0.348-0.916, P = 0.02). As previously noted for necroinflammation similar results, although less significant, were observed for rs12979860, with, as an example, the proportion of fibrosis ≥F2 in patients infected with non-1 genotypes being 0.52 in CT/TT subjects as compared
with 0.62 in CC subjects (P = 0.02; Table S2). Because patient demographic and histological characteristics differed in the two cohorts, we performed stratified analyses to determine whether the effects of IL28B SNPs on fibrosis and its progression were MCE comparable (Fig. S1). Despite different baseline proportions of patients with fibrosis ≥F2, rs8099917 influenced these proportions in both cohorts, although the level of significance after stratification was not reached in the French cohort due to the smaller sample size (Fig. S1A). The SNPs effect differed according to viral genotypes, and this was highly consistent in both cohorts. IL28B rs8099917 did not affect the proportion of fibrosis ≥F2 among genotype 1-infected patients (0.39 in both rs8099917 GT/GG and TT carriers in the French cohort, P = 1.0; 0.53 among GT/GG carriers versus 0.52 among TT carriers in the SCCS, P = 0.8, Fig. S1B).