To determine the zonal distribution of alcohol dehydrogenase in normal and cirrhotic human livers, we measured activities of this enzyme by quantitative cytochemical analysis along the liver cell plate in liver specimens from 10 normal organ donors and from 7 children with extrahepatic biliary atresia cirrhosis. In normal human liver samples, a continuous increase in alcohol dehydrogenase activity was observed along the sinusoid from the periportal to the perivenular hepatocytes (mean extinction units from 16.2 2 10.0 to 58.0 & 14.8). A similar observation was made in cirrhotic nodules, with activity increasing continuously from nodule periphery to center (7.6 f 4.1 to 44.9 2 13.3). This study demonstrates a heterogeneous pattern of alcohol dehydrogenase distribution along the sinusoid in normal human liver specimens. In addition, demonstration of this heterogeneity in human cirrhosis suggests that the cirrhotic liver is able to maintain a parenchymal functional organization, with persistence of metabolic zonation. (HEPATOLOGY 1993; 17:202-205.)
Alcohol dehydrogenase (ADH) (EC 1.1.1.1) is an enzyme responsible for the metabolism of ethanol and other alcohols (1). Most recent reports agree that a prevalent zone 3 distribution of this enzyme exists in rat liver (2-51, and authors suggest that this zonation of ADH may play an important role in the perivenular localization of initial liver damages induced by alcohol in human beings (2-4). Other animal studies, however, failed to show any acinar distribution of ADH (5, 61, or they even suggested predominant periportal activity (7, 8). These discrepancies may be caused by differences in tissue fixation procedures, substrate and cofactors used for the reaction and isoenzymes studied (2-8).
In the human liver, ADH zonal distribution remains poorly documented (9, lo), and many hypotheses are made according to findings in animal studies. It is also not known whether the activity and zonation of ADH