APRI, AST/Platelet ratio index; AST, aspartate aminotransferase; BMI, body mass index; GGT, γ-glutamyl transferase; GSH, glutathione; Palbociclib research buy HALT-C, Hepatitis C Anti-viral Treatment Against Cirrhosis Trial; HCC, hepatocellular carcinoma; HCV, hepatitis C virus; IFN, interferon; SVR, sustained virological response. HALT-C had two major treatment phases (clinical
trials.gov identifier NCT00006164) and an observational phase.5-7 A lead-in phase used full-dose pegylated interferon alpha 2a (Pegasys, Roche) and ribavirin to attempt to achieve sustained virological response (SVR) among patients with advanced liver disease (Ishak fibrosis score of 3 or greater on liver biopsy) who had previously been treated with standard interferon (IFN) with or without ribavirin. Patients who did not achieve SVR were eligible for the randomized phase, a controlled clinical trial of pegylated interferon alfa-2a at a dosage of 90 μg per week for 3.5 years, as
compared with no treatment. The primary endpoint was progression of liver disease, as indicated by death, hepatocellular carcinoma (HCC), hepatic decompensation, or, for those with bridging fibrosis at baseline, an increase in the Ishak fibrosis score of 2 or more points. Most patients entered the randomized trial through the lead-in phase as nonresponders after 20 weeks Daporinad clinical trial of therapy (based on detectable hepatitis C virus (HCV) RNA by Roche Cobas Amplicor assay) or after subsequent breakthrough or relapse. Other patients entered the randomized phase as “express” patients by having failed to clear virus outside of the HALT-C lead-in. All patients also had liver biopsies scheduled at 18 months after randomization and
at the end of treatment 42 months after randomization. Patients continued to be followed in the observational phase for clinical outcomes off therapy for as long as 5 additional years. The median duration of participation in the trial (time from randomization to first outcome or last time known to be outcome-free) was 6.0 years (range, 0-8.7 years). Informed consent in writing was obtained from each patient, and the study protocol was approved by the Institutional Review Committee Selleckchem CHIR99021 of each of the participating centers. GGT activity was measured under code on stored frozen samples (−80°C) by Wako Pharmaceuticals (Richmond, VA) under a clinical trial agreement with the National Institute of Diabetes and Digestive and Kidney Diseases. The normal range was reported as 12-64 IU/L for men and 9-36 IU/L for women. Of the 1,319 patients with GGT measurements, 770 participated in both the lead-in and randomized phases of the trial (blood sample drawn shortly before lead-in), 320 only in the lead-in phase (blood sample drawn shortly before lead-in), and 229 only in the randomized phase (blood sample drawn shortly before randomization). GGT results were available on 95.2% of lead-in patients and 95.