IRON STORAGE, LIPID-PEROXIDATION AND GLUTATHIONE TURNOVER IN CHRONIC ANTI-HCV POSITIVE HEPATITIS

Background/Aims: Little is known about the pathogenesis of liver damag e related to hepatitis C virus. The presence of steatosis or increased ferritin levels, and preliminary data on the relevance of iron as a p rognostic factor prompted us to ascertain whether hepatitis C virus-re lated liver damage might be mediated by iron accumulation. Methods: We evaluated the degree of hepatic inflammation and steatosis, serum fer ritin, transferrin saturation and iron levels, tissue iron concentrati ons and iron index, liver glutathione and malondialdehyde in 33 males and 20 females with chronic hepatitis C virus- or hepatitis B virus-re lated hepatitis (42+11). We also considered six patients with both alc ohol abuse and hepatitis C virus, four males with chronic alcoholic li ver disease and four males with genetic hemochromatosis, giving a tota l of 67. All diagnoses were histologically confirmed. Patients with ci rrhosis were excluded. Results: Our data show that: 1. Steatosis is mo re frequent in hepatitis C virus and hepatitis C virus+alcohol abuse p atients; 2, In males, serum ferritin and tissue iron are significantly higher in hepatitis C virus- than in hepatitis B virus-positive patie nts (p<0.01 and 0.05); transferrin saturation is higher (p<0.05) in he patitis C virus-positive than in hepatitis B virus-positive patients o nly when males and females are considered together; 3. Serum ferritin and transferrin saturation only correlate with liver iron (r=0.833 and r=0.695, respectively, p=0.00001); tissue iron is significantly highe r in hepatitis C virus- than in hepatitis B virus-positive patients (p <0.05); 4. In patients with chronic hepatitis, serum ferritin is a bet ter marker of liver iron storage than transferrin saturation, both in males and in females; 5. Hepatitis C virus-positive patients have high er malondialdehyde levels and activation of turnover of glutathione, p robably in response to free-radical-mediated liver damage: Females hav e lower liver iron levels but similar trends. Conclusions: These findi ngs suggest that hepatitis C virus-related liver damage is characteriz ed by increased iron storage (possibly induced by the virus) which eli cits a free-radical-mediated peroxidation, with consequent steatosis a nd activation of glutathione turnover.