Histological changes in the liver and indices of drug metabolism in alcoholics.

Abstract

The drug metabolizing capacity of the liver was investigated in 27 consecutive alcoholics by comparison of in vivo (antipyrine kinetics) and in vitro (cytochrome P-450) indices of drug metabolism with quantitative histological determinations of fat, trabeculae and non-fatty parenchyma in liver biopsies, and with biochemical liver function tests. The reduced amount of hepatic parenchyma in the biopsies was related to diminished drug metabolizing capacity, both in vivo and in vitro. The accumulation of fat alone did not significantly alter the kinetics of antipyrine, although it was associated with reduced cytochrome P-450 content. The replacement of parenchyma by fibrous tissue resulted in a decrease both in antipyrine clearance rate and cytochrome P-450 content. There was a logarithmic correlation between the kinetic parameters of antipyrine and cytochrome P-450 in the entire series, whereas a linear relationship was found in the alcoholic subjects in the various diagnostic groups. A non-linear relationship was also found between biochemical liver function tests and the in vivo and in vitro indices of drug metabolism. The results demonstrate that drug metabolizing capacity in alcoholics is related to ethanol-induced changes in the liver. quantitative evaluation of hepatic parenchymal changes, together with tests of the functional capacity of the liver, might be of significance value in predicting the ability of alcoholics to metabolize drugs.