036). Among the four liver enzymes measured at baseline (GGT, ALT, AST, and alkaline phosphatase), GGT

had the most robust association with response to therapy and with disease outcomes. Among the other enzymes, lower AST was an independent predictor of week 20 virological response and alkaline phosphatase was an independent predictor of predictor of HCC. ALT was neither an independent predictor of treatment response or of disease outcome. Ibrutinib We examined change in mean GGT activity with other variables for 809 patients who had GGT measured at baseline and at last biopsy (mean of 3.9 years). Mean GGT changed minimally during this period (−2.1 IU/L, P = 0.72), and was unaffected by treatment assignment (P = 0.47). Change in GGT activity was positively correlated with changes in histological steatosis (r = 0.21, P < 0.0001), alkaline phosphatase activity (r = 0.24, P < 0.0001), ALT activity (r = 0.31, P < 0.0001), serum ferritin concentration (r = 0.25, P < 0.0001), and modestly with

Ishak inflammation score (r = 0.078; P = 0.026), but not with change in fibrosis score (r = −0.041, P = 0.25), change in BMI (r = 0.03, P = 0.39), AST/ALT ratio (r = 0.05; P = 0.15), or platelet count (r = −0.04; P = 0.26). Results were similar irrespective of treatment assignment. Particularly striking was the association with change in steatosis and with alcohol drinking, which were independently associated with change in GGT (P < 0.01). The mean change Selleck ABT888 in GGT activity was −42 IU/L for the 274 patients who had a decrease in steatosis, −3 IU/L for the 430 patients with no change, and 44 IU/L for the 189 patients with an increase in steatosis (P < 0.0001). The mean change in GGT was −54 IU/L for the 44 patients who reported stopping drinking, −3 IU/L for the 737 patients whose drinking status

did not change, and 37 IU/L for the 89 patients who reported that they had started drinking (P = 0.019). The association with change in GGT was accentuated when both variables were considered together. The mean change in GGT was −112 IU/L for the 14 patients who stopped drinking and steatosis decreased, 4 IU/L for the 332 patients with no change in drinking or steatosis, and 191 IU/L for the 16 patients who CYTH4 started to drink and steatosis increased. The current report includes several new and confirmatory findings regarding the prognostic significance of GGT activity in chronic HCV. These findings pertain both to treatment response and to disease outcome. We confirmed that higher GGT activity is associated with lower probability of virological response to IFN-based treatment for HCV.9-14 Compared with previous studies, HALT-C was unique in its size, prospective patient characterization, and in the homogeneity of the patient population, all of whom had advanced fibrotic liver disease and previous treatment with IFN.