DIFFERENTIAL DEPLETION OF CAROTENOIDS AND TOCOPHEROL IN LIVER-DISEASE

Carotenoids and tocopherols are major natural protective agents agains t free radical-mediated liver damage, but their levels in diseased liv er are largely uncharted. Therefore we carried out measurements with h igh-pressure liquid chromatography of alpha- and beta-carotene, lycope ne, cryptoxanthin, lutein and zeaxanthin, total retinoids and alpha- a nd gamma-tocopherol. Liver tissue was obtained from percutaneous needl e biopsies, livers of transplant recipients or a donor bank. Compared with controls (transplant donors; n = 13), levels of all carotenoids a nd retinoids were extremely low at all stages of liver disease. Patien ts with alcoholic cirrhosis (n = 11) had 20- and 25-fold decreases of levels of lycopene (p < 0.001) and alpha- and beta-carotene (p < 0.005 ), respectively. Even in subjects with less severe alcoholic liver dis ease (steatosis, perivenular fibrosis, portal fibrosis; n = 14) and in patients with nonalcoholic liver disease (n = 13), levels were four t o six times lower than those in normal subjects. By contrast, levels o f alpha-tocopherol were decreased significantly only in patients with cirrhosis, who displayed a threefold reduction. In the serum of most p atients, lycopene and tocopherol concentrations were not depressed, wh ereas one third of alpha- and beta-carotene levels were low, probably reflecting poor dietary intake. A significant correlation was observed between serum and liver alpha- and beta-carotene levels (p < 0.0001; r = 0.715). However, of the patients with extremely low liver alpha- a nd beta-carotene concentrations, more than half had blood levels in th e normal range, suggesting that liver disease interferes with the upta ke, excretion or, perhaps, metabolism of alpha- and beta-carotene. In the cirrhotic livers of eight candidates for liver transplantation, th e ratios of alpha- and beta-carotene to total retinoids and of beta-ca rotene to retinoids were much higher than those in normal livers, sugg esting some impairment in the conversion of alpha- and beta-carotene t o retinoids. In most cases, even with high ratios, absolute levels of hepatic alpha- and beta-carotene and retinoids were severely depressed . We concluded that, even in the presence of normal serum levels alpha - and beta-carotene, tocopherol and lycopene, patients with cirrhosis have extremely low hepatic levels.