Patients were divided into two groups: (1) patients with no fibrosis progression, defined as difference in the Ishak score of <2 between the biopsies; (2) patients with fibrosis progression, defined as 2 or greater increase in the Ishak score between biopsies. (3) Clinical outcomes analysis: For this analysis, only subjects from the control arm of HALT-C cohort (n = 400) were included because data on the clinical outcomes were prospectively collected over 3.85 years and adjudicated by a panel of three principal investigators using stringent criteria to confirm that a clinical event had indeed occurred. A clinical outcome was defined as one of the following: death, development Dasatinib purchase of ascites, spontaneous bacterial peritonitis,

variceal hemorrhage, hepatic encephalopathy, HCC, and increase in Child-Pugh-Turcotte

score by 2 or more points on two consecutive clinic visits 12 weeks apart. Both studies were approved by the Institutional Review Board of the NIDDK, NIH and both cohorts signed a separate consent form for genetic testing. Genotyping of the rs12979860 SNP was performed on all patients from the HALT-C and NIH cohorts with available DNA samples and who provided genetic consent as described[17] (Supporting Material). PLX4032 Baseline clinical characteristics and laboratory values of these patients and their relationships to fibrosis were examined. Variables analyzed included demographic factors including age, sex, race, and ethnicity, anthropometric indices (body mass index [BMI]), duration of infection, presence of diabetes, and alcohol consumption. The following laboratory and histological tests were included: serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) levels, alkaline phosphatase, total bilirubin, albumin, prothrombin time, platelet count, ferritin, and hepatic steatosis. Baseline variables were compared using chi-square, t test, or analysis of variance. Logistic regression was used to calculate odds ratios for

the relationship between fibrosis Gefitinib solubility dmso progression and IL28B (CC versus CT or TT). Analyses of the combined cohorts included a variable indicating cohort (NIH or HALT-C). Other predictors of fibrosis progression were evaluated and those significant after backward selection were also included in the model. Change in fibrosis, HAI, and ALT were analyzed using an analysis of variance controlling for baseline levels. Clinical outcome rates were estimated using Kaplan-Meier estimates and significance was tested using the log-rank test and Cox proportional hazards regression. Analyses were conducted by cohort and with both cohorts combined. Data are presented as percent or mean and SD unless otherwise noted. SAS (Statistical Analysis Software, Cary, NC) v. 9.2 was used for statistical analyses. A total of 309 patients were followed in NIH natural history studies and 1,382 patients were enrolled into the HALT-C trial.