05 and a final model was SCH727965 molecular weight established with the significant terms only. Additionally, survival analysis was performed to model the time taken for advanced fibrosis to occur. Here, advanced fibrosis was defined if Ishak ≥4. A Cox proportional-hazards regression model was fitted, and the covariates were considered significant if P < 0.05. The proportional hazard assumption was checked and a final model was proposed, considering the significant terms only. All statistical analyses were performed in R,12 using the survival library for Cox regression.13 For the present analyses, 247 patients consecutively attending our center between September 2008 and March 2010 that fulfilled the strict selection

criteria were selected. Patient ABT-263 clinical trial characteristics are outlined in Table 1. The majority of the patients were infected with HCV genotype 1 (52%), although this study included subjects with HCV genotypes 1, 2, 3, and 4. Both males and females were well represented (52% males, 48% females). Median age at infection was 21 years, median disease duration was 25 years, and median age at biopsy was 47 years. Mean biopsy length was 26.3 mm. The FPR distribution resulted in being right-skewed, but approached a normal distribution after log10 transformation (see Supporting Information). The majority of the patients (87%) had minimal to mild histological

activity (grade <9), whereas a minor fraction (13%) showed moderate to severe activity (grading ≥9). Moderate or severe steatosis (grade 2-3) was observed in 20% of the patients. Mean BMI was 25.3 kg/m2. The main reported risk factors for HCV

infection were blood transfusions (75%) and the use of intravenous drugs (23%), with mother-to-child, needlestick, or sexual transmission as the other reported risks. In this cohort, 29 patients were MCE age 0 at infection. Only 1 of these patients acquired the infection vertically, whereas the others received a blood transfusion at birth. IL28B genotypes of patients with absent or mild fibrosis (Ishak <4) and patients with advanced fibrosis (Ishak ≥4) are shown in Table 2. Genotype frequencies did not differ significantly between the two groups, regardless of the analyzed SNP (rs8099917 or rs12979860). Moreover, SNP genotype frequencies did not deviate significantly from Hardy-Weinberg equilibrium expectation at a threshold of P = 0.01. The measured genotype frequencies are consistent to other published reports with HCV-infected patients.6, 7 To evaluate the contribution of genetic and nongenetic factors in the natural history of chronic HCV infection, we performed multiple analyses aimed at the definition of the individual contribution to fibrosis progression in the cohort of patients described above (see Patients and Methods). Here, we evaluated whether the genotype of rs8099917 and rs12979860 polymorphisms could influence fibrosis progression in the liver of HCV-infected patients.