Carbohydrate Deficient Transferrin in a Driver's License Regranting Program

Alcohol and Alcoholism Vol. 47, No. 3, pp. 253–260, 2012 Advance Access Publication 5 March 2012 doi: 10.1093/alcalc/ags013 SCREENING AND IDENTIFICATION Carbohydrate Deficient Transferrin in a Driver’s License Regranting Program Thomas M. Maenhout1, Guido Baten2, Marc L. De Buyzere and Joris R. Delanghe1, * 1 Department of Clinical Chemistry, Ghent University Hospital, De Pintelaan 185, B 9000 Gent, Belgium and 2Dienst herstelonderzoeken, Belgian Institute of Road Safety, Brussels, Belgium *Corresponding author: Tel.: +32-9-3322956; E-mail: (Received 2 September 2011; in revised form 24 November 2011; accepted 9 January 2012) Abstract — Aims: Carbohydrate deficient transferrin (CDT) is a common diagnostic marker for detecting chronic alcohol abuse. For over 2.5 years, it has been used in traffic medicine among subjects applying for driver’s license renewal or regranting in Belgium. We report on data collected during the program and provide an estimation of an applicable cut-off point in forensic situations. Using this cut-off, the success of the driver’s license regranting program is evaluated. Methods: CDT was assayed at Ghent University Hospital by capillary zone electrophoresis, measured on the Capillarys 2™ system, in 3977 subjects applying for driver’s license regranting. Determination of a cut-off was done by using Bhattacharya statistics and by adding a measurement uncertainty interval. The outcome of the program was evaluated by monitoring CDT values for 163 subjects during one entire year. Results: In 3977 subjects (3481 males and 496 females), CDT values were significantly higher in men compared with women, but there is no need for a gender-specific cut-off value. Drunk drivers under the age of 30 have significantly lower CDT values than older subjects, and a separate cut-off could be calculated. A general cut-off of 2.3% CDT was calculated for the entire study population. Using this cut-off value for evaluating the outcome of the program for 163 subjects, the percentage offenders at the beginning (29%) decreased to 8% after 1 year. Conclusion: Applying a marker for chronic alcohol abuse such as CDT for driver’s license renewal or regranting is a powerful tool. Analysis of data collected over 2.5 years reveals a favorable outcome of the program and a useful cut-off point could be determined. INTRODUCTION Diagnosing chronic alcohol abuse is difficult because a majority of the subjects denies or minimizes alcohol abuse and because diagnostic parameters with both high sensitivity and specificity are lacking. From both a medical and from a social perspective, there is a need for early detection and correct judgment of the severity of alcoholism. Indications in the field of forensic medicine are identification of drunk drivers (Gjerde and Morland, 1987; Iffland and Grassnack, 1995; Bortolotti et al., 2007) and license reapplication (Morgan and Major, 1996). Carbohydrate deficient transferrin (CDT) is regarded as the laboratory parameter with the highest diagnostic efficiency (Delanghe and De Buyzere, 2009). Morgan and Major (1996) investigated and observed the potential impact of CDT values on the decision of license reapplication in ‘high-risk offenders’. Iffland and Grassnack (1995) investigated the significance of CDT values in drivers suspected of having driven drunk. At least eight countries in Europe use biomarkers routinely as a part of the clinical evaluation of drunk drivers and to assess alcohol abstinence (Delanghe and De Buyzere, 2009). In Switzerland, Italy and Austria, repeat offenders are sent to therapy and biological markers, including CDT, are measured quarterly for an entire year to monitor alcohol abstinence. After 1 year, if treatment was successful and biomarkers were kept in check, the driver’s license is reinstated. CDT testing has been introduced in Belgium in 2008 within the framework of driver’s license reinstatement. Drunk drivers are invited to participate in an alcohol contract program, in which regular blood controls are integrated. The subject is free to decide whether to participate or not. The blood samples are drawn bimonthly during a 1-year period. Among others, CDT is one of the biomarkers that are used to monitor the driver’s adherence to the abstinence program (Delanghe and De Buyzere, 2009). In view of the numerous caveats and especially for forensic applications, a wellbalanced interpretation is needed. For these purposes, high performance liquid chromatography (HPLC) or capillary zone electrophoresis (CZE) are to be preferred for CDT analysis as their main advantage is the separation of different CDT isoforms. In problem cases, the use of additional alternative tests (e.g. ethyl glucuronide and fatty acid ethyl esters in hair) can be considered. In the present prospective study, the CDT data from this program are analyzed and the possibilities, limitations, the outcome and pitfalls regarding the use of CDT for evaluating driving ability are discussed. MATERIALS AND METHODS Subjects A total of 8318 CDT analyses were carried out on a population of 3977 subjects: 3481 males (87.5%) and 496 females (12.5%). They were all included in a driver’s license regranting program under the control of the Belgian Institute of Road Safety [Belgisch Institut voor Verkeersveiligheid (BIVV)-Institut Belge pour la Sécurité Routière (IBSR)]. The data were obtained over a period of 2.5 years (September 2008–March 2011). Not all data were available for every subject, because of teething problems of the project. No data were excluded from the analysis. The study was approved by the Ethics Committee of Ghent University Hospital (EC/008-2012). Assays CDT was assayed using CZE (Schellenberg et al., 2007), measured on the Capillarys 2™ system (Sebia, France). In this technique, after on-line iron saturation, samples are submitted to high voltage (8200 V) zone electrophoresis in alkaline buffer ( pH 8.8). The transferrin glycoforms are © The Author 2012. Medical Council on Alcohol and Oxford University Press. All rights reserved 254 Maenhout et al. quantified by their peptide bond absorbance at 200 nm. Pherograms were validated using the manufacturer’s software. In case of heterozygous transferrin C-variants (TfC), the % CDT result was corrected for heterezygosity by a factor 2. It is possible to estimate the total amount of disialo-C- and trisialo-C-transferrin, using approximately twice the value of disialo-D- and trisialo-D-transferrin (Wuyts et al., 2001). Determination of a cut-off value for % CDT Determination of a suitable cut-off limit for forensic use was carried out on a major subgroup of 8233 data points in which samples with disturbed transferrin pherograms were excluded. The upper limit of normal (ULN) was calculated as the 99.9th percentile of the normal or gamma distribution extracted out of the population using Bhattacharya analysis (Bhattacharya, 1967) as modified by Naus et al. (1980). In order to interpret the result w (...truncated)