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.