To avoid biases imposed by the above assumption, we decided to use an alternative analysis approach. Thus, we also used a proportional-hazard survival model to analyze the relationship between the above-mentioned explanatory factors and the time Trichostatin A chemical structure it takes to develop

bridging fibrosis or cirrhosis (Ishak ≥4). In agreement with the linear model, the significant variables found with this model were age at infection (P = 1.26E-13), male gender (P = 0.018), HCV genotype 3 (P = 0.004), and steatosis (P = 0.003), whereas the two IL28B polymorphisms had no effect on the estimated hazard of developing advanced fibrosis (Table 4; Fig. 2). From the estimates of the coefficients, we can derive the effect on the hazard. Thus, holding the other covariates constant, each additional year

at infection produces a highly significant increase of the hazard of advanced fibrosis by a factor of 1.121 (95% confidence interval [CI] =1.088-1.155) or 12.1%. This effect is clearly evident when plotting the estimated survival functions for three representative infection times (0, 20, or 40 years of age, respectively; Fig. 2). Indeed, the three survival functions are well separated and their corresponding CIs do not overlap. Conversely, the corresponding estimated survival functions by IL28B genotype are clearly overlapping, underscoring the lack of any effect of these variables. Neratinib concentration Furthermore, the effect of HCV genotype, gender,

and steatosis were also significant, but their estimates had wider CIs (Table 4). It is now well established that genetic variations in the region of the IL28B gene on chromosome 19, coding for IFN-λ3, are strongly associated with the achievement of treatment-induced or spontaneous viral clearance in individuals infected with HCV.11 In particular, numerous studies have shown that individuals with the C/C genotype at the rs12979860 SNP (i.e., “protective” or “responder” genotype) have higher rates of rapid, sustained virological response to treatment with the current standard MCE of care (i.e. PEG-IFN/RBV), compared to those carrying the T allele (C/T and T/T genotypes). More recently, it has also been proposed that the poor response IL28B variants, in hepatitis C patients, are also associated with lower pretreatment low-density lipoprotein cholesterol levels,17, 18 hepatic steatosis,18, 19 and insulin resistance,19 compared to the “responder” genotype. However, it is still unclear whether the genetic variation at the IL28B locus affects the severity and pace of the progression of liver disease. Indeed, though some investigators found that the unfavorable rs12979860 T/T gene pattern was associated with worse liver fibrosis, others did not replicate this finding. Bitetto et al.