The Activity of β-Hexosaminidase (uHex) and y-Glutamyi-transferase (uGGT) in Urine as Non-Invasive Markers of Chronic Alcohol Abuse: II. Opiate-Dependent Subjects Receiving Methadone Substitution

Abstract

The usefulness of beta-hexosaminidase (uHex) and gamma-glutamyltransferase (uGGT) activity in urine as markers of chronic alcohol abuse was examined in male methadone programme participants. The group consisted of 24 non-abusing and 21 alcohol-abusing men. It has been demonstrated that the uHex test is one of the best alcohol abuse markers for opiate-dependent individuals (Receiver Operating Characteristic (ROC) area under the curve (AUC) 0.82, sensitivity 0.70, specificity 0.82). The uGGT test can be used as a marker of alcohol abuse in opiate-dependent men, however, its parameters are worse than those of uHex (ROC AUC 0.73, sensitivity 0.71, specificity 0.77). Among serum markers, only the relative amount of carbohydrate-deficient transferrin (s%CDT) has parameters sufficient for diagnostic use (ROC AUC 0.74, sensitivity 0.60, specificity 0.86). Factors other than alcohol can render the commonly used sGGT and sHex tests useless (differences between means for abusing and abstinent patients were insignificant, AUC ROC were lower than 0.7-0.65 and 0.69, respectively). Their good parameters, low costs, ease of use and non-invasive character are all features which make uHex and uGGT highly useful tools in the detection of chronic alcohol abuse in opiate-dependent patients participating in a methadone substitution programme.

Combining markers of nephrotoxicity and hepatotoxicity for improved monitoring and detection of chronic alcohol abuse

“…The present study confirmed the results of our preliminary work on uHex utility in alcohol-dependent men (21,22), and showed negligible bias from endogenous inhibitors of the enzyme. This finding and the slightly, albeit non-significantly, higher AUC value ( Table 2) mean that uHex is superior to eAAP as a possible clinical marker.…”

“…Factor analysis of the markers studied revealed that the liver and kidney origins of the markers were independent factors, and showed significant correlation within, but not between, the two marker groups. These findings indicate that these marker groups represent metabolically unrelated events, which is in agreement with previous studies (20)(21)(22)(23) and suggests that combining representatives of these marker groups would be of diagnostic advantage. This indication was confirmed by the stepwise discriminant analysis, which showed highest diagnostic potential for the combination of GGT and uHex data into a composite marker and no significant gain from adding any of the remaining markers to this combination.…”

“…This may be due to different gender, age, BMI (14,33), ethnicity, alcohol intake and incidence of tobacco smoking in different patient cohorts studied (14,34), and disparate cutoff values employed (21,22,35). Distinct drinking patterns may also be of substance, as some reports have shown ''sensitization'' after chronic heavy drinking (34,36).…”

“…However, because of its relatively large molecular size (130-140 kDa), serum Hex should not normally be filtered through the glomeruli and contribute to urinary Hex (uHex) activity. In fact, a number of studies have revealed a lack of correlation between serum Hex and uHex in alcohol abusers (20)(21)(22). Hence, alcohol abuse-related elevation of urinary activity of Hex and AAP represents a potential tool for non-invasive diagnosis of such abuse.…”

“…Hence, alcohol abuse-related elevation of urinary activity of Hex and AAP represents a potential tool for non-invasive diagnosis of such abuse. There is a slowly growing body of evidence showing the potential clinical utility of urinary markers in diagnosing and monitoring alcohol abuse (20,21,23,24).…”