Trace elements are involved in chronic liver diseases because these elements may have a direct hepatic toxicity or may be decreased as a consequence of the impaired liver function, particularly in patients with alcoholic cirrhosis and/or malnutrition. In this study, we determined plasma and erythrocytes trace elements in 50 inpatients with nonalcoholic chronic liver disease (11 with biopsy-proven chronic hepatitis, 39 with cirrhosis [16 in stage A according to Child-Pugh criteria, 23 Child B+C]), and in a control group of 10 healthy subjects by the proton induced x-ray emission method. The relationship between trace element concentration and the extent of liver damage, the nutritional status (by anthropometric evaluations), and various blood markers of oxidative stress--reduced glutathione, total lipoperoxides and malonyldialdehyde--was investigated. We found that cirrhotics had a significant decrease of Fe, Zn, Se, and GSH levels in the plasma and of GSH and Se in the erythrocytes with respect to the control and chronic hepatitis groups. GSH levels were related to the degree of liver damage; a significant direct correlation was observed among Se, Zn, and GSH plasma values and between GSH and Se in the erythrocytes. The trace element decrease was, on the contrary, independent of the degree of liver function impairment and only partially affected by the nutritional status. Data indicate that liver cirrhosis, even if not alcohol related, induces a decrease of Se and Zn and that, in these patients, an oxidative stress is present, as documented by the significant correlation between Se and GSH. The plasma Br level was higher in cirrhotics with respect to the control and chronic hepatitis groups.

Alcohol changes the progression of hepatitis C virus (HCV)-related chronic liver disease and may affect the outcome of interferon therapy. The ethanol intake of 245 patients with biopsy-proven chronic hepatitis C with or without cirrhosis, its interaction with laboratory and histological parameters common to alcohol and HCV-mediated liver damage, and its effects on therapy were evaluated. The results show that 60-70% of subjects regularly consumed alcohol (median intake >40 g/day in about 30%). Less than 50% stopped drinking after being diagnosed as having liver disease. Ethanol intake affected: fibrosis, especially in women, HCV RNA levels, which were significantly lower in abstainers than in drinkers (0.6 +/- 0.3 vs 6.9 +/- 5.9 Eq/ml x10(6); P < 0.01), and response to interferon therapy. The number of responders decreased as ethanol intake increased. There were less abstainers than drinkers among non-responders (10.7% vs 63.1% respectively; P < 0.001). Data indicate that alcohol will induce and worsen liver damage and, in subjects with chronic liver disease who continue to drink, adversely affect their response to treatment.

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.