Novel Use of Biomarkers and Their Combinations for Detecting Excessive Drinking

Excessive alcohol consumption and consequent medical disorders create a major burden for modern health care. In addition to medical and social problems, excessive drinking causes considerable strains on the national economy. In order to improve the diagnosis and treatment of patients suffering from ethanol-related health problems, reliable and accurate methods for recognizing excessive alcohol consumption in its early phase need to be developed. Currently, excessive drinkers tend to escape detection, which may lead to delays in intervention. The present study was set out to develop new approaches for detecting excessive drinking based on conventional and new laboratory tests and their combinations and to address the relationships between such markers and alcoholic liver disease. Conventional laboratory markers of excessive drinking (GGT, CDT, MCV, AST, ALT), a mathematically formulated combination of GGT and CDT, and autoimmune responses to proteins modified with acetaldehyde, the first metabolite of ethanol, were measured in alcoholics with or without liver disease, moderate drinkers and abstainers. Cytokine profiles of subjects were also studied in order to clarify the associations between alcohol intake and pathogenesis of alcoholic liver disease. The results show that even moderate drinking may increase levels of gamma-glutamyl transferase (GGT). When GGT was combined logarithmically with carbohydrate-deficient transferrin (CDT), the diagnostic performance of the combination GGT-CDT was found to markedly exceed that of the traditional markers, reaching a sensitivity of 90 % whereas the sensitivities of its parent components remained at 63 % (CDT) and 58 % (GGT). Alcohol consumption was also found to induce alterations in the immune system. An association between cytokine levels and alcohol use was observed, with most evident alterations in alcoholics with liver disease. Pro-inflammatory cytokines (IL-2, IL-6, IL-8, TNF-α) were found to increase in alcoholic liver disease whereas the levels of anti-inflammatory cytokines, particularly TGF-β1 showed a slight decrease. Acetaldehyde adducts are formed when acetaldehyde reacts with proteins and cellular constituents. Antibodies directed against acetaldehyde-modified proteins were found in the circulation of alcoholic patients. The highest anti-adduct IgA and IgG titres occurred in patients with alcoholic liver disease, while specific class IgM antibodies were most abundant in alcoholics without liver disease. The possible usefulness of anti-adduct IgA as a marker of excessive drinking was subsequently studied in alcoholics without liver disease, and the mean anti-adduct IgA levels were significantly higher than those in the moderate drinkers or abstainers (p < 0.001), while the difference between the moderate drinkers and abstainers was also significant (p < 0.05). Mean daily ethanol consumption during the previous month was found to correlate significantly with anti-adduct IgA levels. Based on these findings, anti-adduct IgA antibodies could serve as markers of alcohol con-