Alcoholic Liver Disease Associated with Increased Gamma-Glutamyltransferase Activities in Serum and Liver

Abstract

Chronic alcohol consumption leads to increased activities of gamma-glutamyltransferase (GGT) in the serum which are associated with an enhancement of GGT activities in the liver. These findings suggest that increased GGT activities commonly found in alcoholic liver disease can be ascribed primarily to hepatic enzyme induction rather than to liver cell injury, since hepatic GGT activities were increased but not reduced. Moreover, at the fatty liver stage the fetal form of GGT in the serum is much higher in activity that the adult form, whereas the reverse constellation can be found in patients with alcoholic liver cirrhosis. Thus, these preliminary data suggest that the determination of various forms of GGT in the serum of alcoholics may be useful in establishing the particular stage of alcoholic liver disease by a simple enzyme test in the serum.

The gamma-glutamyltransferase (GGT) catalyzes the transfer of the gamma-glutamyl residue to amino acids or peptides and may function in the regulation of the glutathione level and amino acid transport through cell membranes (Meister, 1974). A fetal and adult form of GGT activity has been described in the serum more recently, and differentiation was achieved using Concanavalin-A Sepharose column chromatography (Köttgen et al., 1977).

Chronic alcohol consumption leads to striking elevations of serum gamma-glutamyltransferase activities (Rosalki and Rau, 1972); Teschke et al., 1978), but the mechanism of the enhancement of serum GGT activity is still disputed. It has been suggested that increased serum GGT activities associated with alcoholism might be caused by an increased release of GGT activity from the liver due to hepatic injury (Singer and Kaplan, 1978) or result from hepatic enzyme induction (Teschke et al., 1977; Ishii et al., 1978; Shaw and Lieber, 1979). Studies in experimental animals have indeed shown that chronic alcohol consumption increases (Teschke et al., 1977; Ishii et al., 1978; Shaw and Lieber, 1979) or depresses (Singer and Kaplan, 1978) rat liver gamma-glutamyltransferase activities.

The present paper will focus on the mechanism involved in the enhancement of serum GGT activity in patients with a history of chronic alcohol consumption; moreover, an attempt is made to correlate alterations of the fetal and adult form of serum GGT activity with various stages of alcoholic liver disease.