Carbohydrate-Deficient Transferrin in Serum: a New Marker of Potentially Harmful Alcohol Consumption Reviewed

TLDR

Over the past 16 years, studies have identified carbohydrate‑deficient transferrin, a marker of alcohol abuse composed of isoforms lacking terminal trisaccharides, whose mechanism is thought to involve acetaldehyde‑mediated inhibition of glycosyl transfer. Carbohydrate‑deficient transferrin may thus offer a new possibility of diagnosing alcohol‑related disorders. Such isoforms have so far been detected by charge‑based methods such as isoelectric focusing, chromatofocusing, and anion‑exchange chromatography combined with immunological detection. The abnormality rises after 50–80 g ethanol/day for at least a week, normalizes over ~15 days, and in 2,500 subjects shows 82 % sensitivity and 97 % specificity, with rare false positives mainly in severe liver disease or transferrin variants, while being largely independent of other conditions and liver disease.

Abstract

During the last 16 years an increasing number of studies have indicated a new diagnostic marker of alcohol abuse, unrelated to any of the conventional markers of alcoholism. This marker, now called carbohydrate-deficient transferrin, consists mainly of one or two isoforms of transferrin that are deficient in their terminal trisaccharides. Such isoforms have so far been detected by methods based on charge, i.e., isoelectric focusing, chromatofocusing, and anion-exchange chromatography of various designs combined with immunological detection techniques. This transferrin abnormality measures an accumulated effect of alcohol consumption, appearing after regular intake of 50-80 g of ethanol/day for at least one week and normalizing slowly during abstinence (half-life = about 15 days). To summarize all studies to date, approximately 2500 individuals have been examined, with a total clinical sensitivity of 82% and a specificity of 97%. False-positive results have only occasionally been reported: in a few patients with severe liver disease, usually primary biliary cirrhosis and chronic active hepatitis; in patients with genetic D variants of transferrin; and in patients with (and some carriers of) a recently identified inborn error of glycoprotein metabolism. The mechanism behind the transferrin abnormality is unknown but an acetaldehyde-mediated inhibition of glycosyl transfer has been suggested. Carbohydrate-deficient transferrin may thus offer a new possibility of diagnosing alcohol-related disorders. Its measurement is little affected by other conditions and, contrary to conventional markers of alcohol abuse, is apparently largely independent of concomitant liver disease.