In alcohol-related liver disease, free radicals play a part in the pathogenesis of liver damage and may influence cell turnover. The aim of this study was to correlate lipid peroxidation, anti-oxidant defense and iron metabolism with cell proliferation and apoptosis in alcoholic liver injury, also by comparison with virus-related liver disease. In 55 patients, i.e. 10 with chronic alcoholic liver disease [ALD], 34 with HCV-related [HCV] and 11 with HBV-related chronic hepatitis [HBV], we investigated: serum ferritin, liver tissue iron (atomic absorption), cysteine, reduced/oxidized glutathione (HPLC), malondialdehyde (fluorometric assay); histology with hepatocyte proliferation (Ki67 monoclonal antibody) and apoptotic index (ISEL). Ferritin and iron levels did not differ between HCV and ALD, but were both significantly higher in HCV and ALD than in HBV (p<0.05). Malondialdehyde levels were significantly higher in ALD and HCV than in HBV (p<0.0001 and p<0.05) and correlated with both iron (r=.597, p<0.0001) and ferritin (r=.437, p<0.0025). Glutathione levels were significantly lower in ALD than in HCV or HBV (p<0.05), while cysteine levels were significantly higher (p<0.05). The apoptotic index was slightly lower in ALD, with apoptosis occurring more frequently in the centrilobular area, while ALD had fewer proliferating hepatocytes, both overall (p<0.02) and in the periportal and centrilobular areas. This study confirms that chronic alcohol intake:

  1. induces more peroxidative damage, correlated with iron loading;

  2. reduces antioxidant defense, lowering reduced glutathione liver availability;

  3. induces an accumulation of cysteine, a glutathione precursor/metabolite in the liver, probably due to gGT induction;

  4. correlates with a lesser extent and different distribution of hepatocyte proliferation and apoptosis than in viral liver damage.

This last finding may explain the different type of liver cirrhosis deriving from alcoholic liver damage and the lower cancer risk.