Increased serum gamma-glutamyl-transpeptidase concentration is associated with nonalcoholic steatosis and not with cholestasis in patients with chronic hepatitis C

Background and Aim:  Increased pretreatment gamma-glutamyl-transpeptidase (γGT) is common in patients with chronic hepatitis C and with little or no alcohol consumption. The mechanism involved in this phenomenon is unclear, and the aim of this study was to investigate factors associated with increased γGT levels, specifically looking at the role of cholestasis that frequently accompanies hepatitis C. Methods:  Fifty patients with chronic hepatitis C enrolled in two trials of antiviral treatment, 25 with normal and 25 with elevated pretreatment γGT levels, were retrospectively selected. In addition to the common liver function and virological tests, other values measured were serum bile acid concentration and composition by gas-chromatography as a sensitive index of cholestasis, and liver biopsy scores for cholestasis and steatosis in addition to siderosis, fibrosis and inflammation. Results:  Total mean serum bile acid concentration was 11.6 ± 1.4 μmol/L and 8.5 ± 1.2 μmol/L (not significant) in patients with elevated and with normal γGT, respectively, and individual bile acid composition was similar in the two groups. By univariate analysis, serum γGT level was linearly related to total serum bile acid (P < 0.05) and to cholestasis score (P < 0.001) among other variables, but steatosis score (P < 0.001) and Knodell score (P < 0.04) were the only variables independently associated with elevated serum γGT level by multivariate analysis. Conclusions:  Increased serum γGT level in patients with chronic hepatitis C is associated with liver steatosis and fibrosis, and indicates more advanced liver disease rather than reflecting the cholestasis that often accompanies this condition.