The significance of alpha-glutathione S-transferase determination in patients with chronic liver diseases.

BACKGROUND: Alpha-glutathione S-transferases (alpha-GST) are the ''basic'' class of a large family of enzymes, ubiquitarly distributed in the cells, particularly in the hepatocytes. Their principal biological function is the detoxification of the cells by conjugating glutathione with various electrophiles and hydroperoxides.

METHODS: We evaluated plasma alpha-GST in comparison to aminotransferase values (ALT) in 234 patients: 18 healthy volunteers, 51 chronic alcohol abusers with (22) or without (29) chronic liver damage and 165 with chronic HCV infection (32 ''apparently'' healthy carriers of HCV infection, 88 with a biopsy-proven chronic hepatitis (CH), 48 treated with interferon, 15 with well compensated and 12 with decompensated liver cirrhosis (LC) and 18 with hepatocellular carcinoma (HCC). Alpha-GST were determined on the venous blood samples after an overnight fast by Hepkit Alpha-Biotech (Biotrin International, Dublin, Ireland).

RESULTS: Control values: <8 ng/ml (range 2.7-6.3). In alcoholics we found a constant increase in 31% of patients without liver disease, in which ALT levels proved constantly normal, and in 13.6% of cirrhotics, without significant correlation among plasma values of alpha-GST, gamma-GT or alcoholemia. In ''healthy'' HCV-carriers, HCV-RNA determination selected 21 subjects positive for viral replication, while 11 were negative. HCV-RNA negative subjects had constant normality of plasma alpha-GST values, while in those HCV-RNA positive alpha-GST increased in 57% of cases. In patients with HCV-related chronic liver disease, alpha-GST proved higher than normal in 80.6% patients with CH, in 40% well-compensated and in 8.3% decompensated cirrhotics and in 33.3% of patients with HCC. No statistically significant correlation was observed between alpha-GST and other liver tests in all groups studied. In patients treated with interferon (6 MU x 3/weekly of alpha-interferon) alpha-GST plasma values were significantly higher in relapsers with respect to responders or not to interferon treatment and during the treatment only in relapsers, while ALT returned to normal values, alpha-GST did not change and, in some cases, increased further. No significant correlation was observed between response to treatment, ALT, alpha-GST and HCV-RNA plasma levels in all groups of CH patients.

CONCLUSIONS: Data indicate that in patients with chronic liver disease with different aetiologies, plasma alpha-GST determination may be useful for discovering a liver involvement also when ALT are normal. In patients with HCV-related CH, plasma alpha-GST values may be utilized as reliable markers in monitoring the response to interferon treatment.