METHOD-DEPENDENT CHARACTERISTICS OF CARBOHYDRATE-DEFICIENT TRANSFERRIN MEASUREMENTS IN THE FOLLOW-UP OF ALCOHOLICS

Alcohol & Alcoholism Vol. 39, No. 1, pp. 59–63, 2004 doi:10.1093/alcalc/agh021, available online at www.alcalc.oupjournals.org METHOD-DEPENDENT CHARACTERISTICS OF CARBOHYDRATE-DEFICIENT TRANSFERRIN MEASUREMENTS IN THE FOLLOW-UP OF ALCOHOLICS PETRA ANTTILA1, KIMMO JÄRVI2, JAANA LATVALA1 and ONNI NIEMELÄ1,3,* Departments of 1Clinical Chemistry and 2Psychiatry, EP Central Hospital, Seinäjoki and 3University of Tampere, Tampere, Finland (Received 4 August 2003; first review notified 18 September 2003; in revised form 20 October 2003; accepted 29 October 2003) Abstract—Aims: There are only limited data comparing the diagnostic characteristics of carbohydrate-deficient transferrin (CDT) measurements in assays for excessive alcohol consumption under controlled conditions. Methods: We compared different CDT assays and the conventional laboratory markers of ethanol consumption, γ-glutamyl transferase (gamma-GT) aspartate aminotransferase (AST) and mean corpuscular volume (MCV) in the assessment and follow-up of 36 alcoholics (31 men, five women, mean age 44 years), who were admitted for detoxification. Detailed interviews to assess the amount of alcohol consumption were carried out for each patient. A hospital follow-up with supervised abstinence for 8 ± 4 days (range 5–19 days) was carried out for 17 patients. Controls were 30 apparently healthy individuals (22 men, eight women, mean age 49 years), who had no history of hazardous drinking. Results: At the time of admission, the %CDT method, which excludes the trisialotransferrin isoform from the measurement, yielded elevated values in 69% of the patients, compared to 61% for CDTect. The corresponding sensitivities for gamma-GT, AST and MCV were 61, 56 and 47%, respectively. The self-reported alcohol consumption for a period of 1 month prior to admission showed a stronger correlation with the %CDT results (r = 0.59, P = 0.0003) than with the CDTect results (r = 0.36, P = 0.04), GT (r = 0.40, P = 0.02) or AST (r = 0.35, P = 0.05). During follow-up with supervised abstinence the mean %CDT values were found to show a slower rate to normalization (mean 14 ± 4 days) than the CDT values measured with the CDTect method (mean 10 ± 5 days) (P < 0.05). Conclusions: The data indicate distinct differences and method-dependent rates of normalization in CDT assays, possibly reflecting different degrees of transferrin desialylation in the alcoholics. The present findings should be considered in studies on alcohol markers for monitoring abstinence. INTRODUCTION We designed this study to compare the characteristics of the different CDT methods in the detection and follow-up of alcoholics, who were admitted for detoxification. For comparison, the conventional alcohol markers (GT, AST, MCV) were also measured. The data suggest distinct differences between the different CDT assays in monitoring alcohol drinking and abstinence. Sialic acid-deficient isoforms of transferrin are known to increase as a result of excessive alcohol consumption. Such isoforms have traditionally been referred to as CDT (carbohydrate-deficient transferrin, desialotransferrin), and their measurements have been widely used as diagnostic tools for detecting alcohol-related health problems. However, the interpretations of the assay results have suffered from a lack of uniform international standardization (Arndt, 2001; Helander et al., 2001; Conigrave et al., 2002; Helander, 2002; Tagliaro et al., 2002). In healthy people, the most common transferrin isoform is tetrasialotransferrin, whereas in alcoholics, various degrees of sialic acid-deficient isoforms are generated (Stibler, 1991; Allen et al., 1994; Helander et al., 2001). Usually, the definition of CDT has referred to those with 0–2 or 0–3 sialic acid side chains (Stibler, 1991; Allen et al., 1994; Arndt, 2001; Helander, 2002). Various methods with different reactivities to different transferrin isoforms are currently available. The diagnostic characteristics of such methods in the clinical assays for detecting alcohol misuse have, however, not been fully established (Scouller et al., 2000). The new %CDT assay, which excludes the trisialo isoform (the isoform with three sialic acid side chains) from the measurement, has recently been suggested to yield improved specificity as compared to the conventional CDTect method, which has previously been the most widely used CDT assay (Anton et al., 2001). MATERIALS AND METHODS Patients and control subjects We studied 36 heavy drinkers (31 men, 5 women, mean age 44 ± 10; range 24–65 years), who were admitted for detoxification, and 30 apparently healthy control subjects (22 men, 8 women, mean age 49 ± 13; range 27–75 years). All the alcoholic patients showed a well-documented history of continuous alcohol consumption or binge drinking, which consisted of 132 ± 71 (mean ± SD) g/day during the 4-week period prior to sampling. The documentation of alcohol misuse was based on detailed personal interviews using a time-line follow-back technique. The patients were asked how many drinks of alcohol (standard drink = 12 g of ethyl alcohol corresponding to one beer, one glass of table wine or 3 cl 40% proof spirit) they had consumed during the: (1) 24 h, (2) 1 week and (3) 4 weeks preceding admission. The mean duration of abstinence prior to sampling was 1.8 ± 2.0 (range 0–6) days. A follow-up with supervised abstinence during hospitalization for 8 ± 4 (range 5–19) days was carried out with 17 patients. Blood-alcohol concentrations were controlled by repeated analyses from breath air. The main clinical and laboratory characteristics of the study population are summarized in Table 1. * Author to whom correspondence should be addressed at: EP Central Hospital, Laboratory, FIN-60220 Seinäjoki, Finland. Tel.: +358 6 415 4719; Fax: +358 6 415 4924; Email: 59 Alcohol & Alcoholism Vol. 39, No. 1 © Medical Council on Alcohol 2004; all rights reserved 60 P. ANTTILA et al. Table 1. Clinical and laboratory characteristics of the study population Parameter Alcoholics Controls n Men/Women Age (years) Ethanol consumptiona (g/day) CDT (%CDT method) (%) CDT (CDTect method) (U/l) GT (U/l) AST (U/l) MCV (fl) Bilirubin (µmol/l) Albumin (g/l) 36 31/5 44 ± 10 132 ± 71**** 4.9 ± 2.7**** 29 ± 15**** 185 ± 291**** 65 ± 50**** 96 ± 5.0** 17 ± 8.6 44 ± 4.9 30 22/8 49 ± 13 0.9 ± 1.7 2.0 ± 0.4 14 ± 5.6 26 ± 11 32 ± 28 92 ± 3.5 14 ± 5.5 42 ± 2.7 The values are presented as mean ± SD. *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001. aMean daily consumption from the past four weeks prior to sampling. CDT, carbohydrate-deficient transferrin; GT, γ-glutamyl transferase; AST, aspartate aminotransferase; MCV, mean corpuscular volume. For reference values, see Methods section. The controls were either abstainers (n = 20; 16 men, four women, mean age 47 ± 9 years) or social drinkers (n = 10; six men, four women, mean age 55 ± 12 years) whose mean daily ethanol consumption did not exceed a mean of 15 g (...truncated)