Use of Enzymes for the Diagnosis of Alcohol-Related Organ Damage

Abstract

Elevated levels of serum enzymes are frequently associated not only with alcohol- related organ damage but also with excessive alcohol consumption and alcoholism without significant tissue injury. However, both in the early detection of alcoholism as well as also in the diagnosis of alcohol-related diseases the sensitivities and specificities of these enzyme markers vary considerably. They may be influenced by nonalcohol-related diseases, enzyme-inducing drugs, nutritional factors, metabolic disorders, age, smoking, etc. Consequently, we have neither a single laboratory test - enzyme marker - nor a test combination that is reliable enough for the exact diagnosis between alcohol- and nonalcohol-related organ damage. In most cases it is possible to determine the tissue from which the elevated enzyme is derived, but only occasionally enzyme changes reflect the quantity of the tissue injury. Gamma-glutamyltransferase (GGT) is the most widely used laboratory marker of alcoholism and heavy drinking, detecting 34-85% of problem drinkers and alcoholics. However, the unspecificity of increased serum GGT limits its use for general screening purposes. Its value in the follow-up of various treatment programs, however, is well established. An elevated level of serum aspartate aminotransferase (ASAT) and alanine aminotransferase (ALAT) in an alcoholic or a heavy consumer indicates alcohol-induced organ damage. The use of test combinations significantly improves the information received with single serum enzyme determinations. An ASAT/ALAT ratio greater than 1.5 can be considered as highly suggestive for the alcoholic etiology of the liver injury. Still better discrimination between alcoholic and nonalcoholic origin of the liver disease may be achieved by the determination of the ratio of GGT to alkaline phosphatase. If this ratio exceeds 1.4 the specificity of the finding in favor for alcoholic liver injury is 78%.

Angiotensin-Converting Enzyme Activity in Experimental Alcoholic Fatty Liver of the Rat

“…Therefore, the cause for increased serum level of these en zymes, observed in some alcoholics, seems to be due rather to liver cell injury [17]. An alternative interpretation could be that the experimental rat model may serve as an ap propriate tool for studying interaction be tween alcohol and GGT, but that it fails in testing other enzymatic activities [17], On the other hand, in the above mentioned in vestigation in man, approximately 30% of the patients had elevated serum ACE levels [9], whereas serum GGT activity, the most widely used laboratory marker of alcoholism and heavy drinking, detects 34-85 % of prob lem drinkers and alcoholics [18].…”

Laboratory Markers of Alcoholism

“…Alcohol per se does not cause an elevation [9]. Since almost all other liver dis ease can cause a rise in serum AST, this find ing has a low specificity even in detecting alcoholic liver disease.…”

“…GGT is synthesized in the endoplasmic reticulum of hepatocytes, transported to the plasma membranes through the Golgi apparatus and subse quently leaks into the blood and the bile [9], Histochemically GGT is normally seen in the sinusoidal membrane of the hepatocyte and in bile canaliculi, but in alcoholic livers a diffuse staining is also seen in the cyto plasm of hepatocytes [10]. Both serum and hepatic activities of GGT increase following chronic alcohol consumption [8,11,12], but the exact mechanisms responsible for this increase are not yet clear.…”

“…Induction of syn thesis is probably a major factor and has been demonstrated both in vivo [ 12] and in vitro in a cultured rat hepatoma cell line [13]. However, impaired biliary secretion and hepatic clearance may also contribute [9], Certainly elevation of serum GGT pre cedes histological evidence of alcohol-in duced liver damage [14].…”

“…It is not increased following acute alco hol consumption alone [17] and falls to nor mal after several weeks abstinence [9], Un fortunately specificity is a problem since many other conditions lead to elevation of serum levels. These include other liver dis- Thus, although serum GGT has the advan tages of ready availability and wide accep tance resulting in much information about its correlation with alcohol intake, it has become apparent in recent years that both its sensitivity and specificity are too low for it to be regarded as a reliable laboratory marker of alcoholism.…”