Abstract
Increased γ-glutamyl transferase (GGT) activity is associated with liver injury and with mortality in the general population. Less is known about its association with chronic hepatitis C (HCV) outcomes. We examined GGT as a predictor of both virological response to treatment and long-term clinical outcomes in the Hepatitis C Anti-viral Treatment Against Cirrhosis Trial (HALT-C). HALT-C enrolled patients with advanced liver disease (Ishak fibrosis score ≥3) in two phases: a lead-in to establish lack of sustained viral response with full dose pegylated interferon (IFN) and ribavirin followed by a 3.5-year randomized trial with low-dose IFN. Low-dose IFN did not prevent liver disease progression, and patients were then followed for up to an additional 5 years off therapy. Analyses were performed for 1,319 patients who had GGT measured prior to initiation of treatment. Increases in risk with each increase in quintile of GGT (10-57, 58-89, 90-139, 140-230, 231-2,000 IU/L) were determined by logistic regression for treatment response or Cox regression for clinical outcomes. Baseline GGT was associated with male sex, nonwhite ethnicity, diabetes and insulin resistance, interleukin (IL)28B rs12979860 CT and TT genotypes, and numerous markers of liver disease injury and severity. In the lead-in phase, increasing GGT was strongly associated with diminished week 20 response, end of treatment response, and sustained virological response in both univariate and multivariate analyses controlling for factors known to be associated with treatment response (P < 0.0001). GGT was also associated with all clinical outcomes in univariate and multivariate analysis (P < 0.05) except for hepatocellular carcinoma (P = 0.46 in multivariate analysis). CONCLUSION: GGT is an independent predictor of both virological response and clinical outcomes among patients with advanced liver disease due to HCV.