Biomarkers of Ethanol Consumption - studies on carbohydrate-deficient transferrin, sialic acid and traditional markers

Abstract

Päihteiden käytön suoraan tai välillisesti aiheuttamat sairaudet ovat yksi tämän päivän merkittävimmistä kansanterveysongelmista Suomessa. Viime vuosina erityisesti naisten ja nuorten alkoholinkäyttö on ollut huolestuttavassa kasvussa.

Alkoholin suurkuluttajien tunnistaminen terveydenhuollossa on perinteisesti ollut vaikeaa silloin, kun potilailla ei vielä ole pitkälle edenneitä alkoholisairauksia tai ilmiselvää riippuvuutta. Kun ongelma on edennyt vaikean sairauden tai riippuvuuden asteelle, tunnistaminen on helppoa, mutta potilaan ennuste on silloin jo merkittävästi huonompi. Tämän vuoksi on ensiarvoisen tärkeää tunnistaa alkoholin riskikulutus mahdollisimman aikaisessa vaiheessa. Tässä tunnistamisessa myös oikein suunnatuilla laboratoriokokeilla on tärkeä merkitys.

Tunnetuimpia tähän tarkoitukseen käytettyjä laboratoriokokeita ovat GT, ASAT, ALAT ja MCV. Niistä jokaisella on kuitenkin omat heikkoutensa, joista merkittävin on kenties se, että myös monet muut syyt kuin alkoholin suurkulutus nostavat näiden laboratoriokokeiden arvoja. Viimeaikaisten tutkimusten perusteella hiilihydraattivajaa transferriini (carbohydrate-deficient transferrin, CDT) voisi olla käyttökelpoinen laboratoriokoe määritettäessä haitallista alkoholinkulutusta. Myös seerumin siaalihappopitoisuutta on ehdotettu uudeksi alkoholinkulutuksen osoittimeksi. Tässä tutkimuksessa verrattiin CDT:n eri määritysmenetelmiä, siaalihappoa ja perinteisiä laboratoriokokeita alkoholistien tunnistamisessa ja seurannassa. Tutkimuksen aikana kehitettiin myös uusi tapa aiemmin esitellyn γ-CDT-yhdistelmämarkkerin määrittämiseksi. Nyt käytettiin hyväksi uudemman %CDT-määrityksen tuloksia, jolloin alkoholistien tunnistamisen tarkkuus entisestään parani.

Tämän tutkimuksen tulokset saattavat osoittautua kaikkein hyödyllisimmiksi tutkittaessa liiallista alkoholinkäyttöä naisilla ja maksasairailla potilailla sekä seurattaessa vieroitushoidossa olevien potilaiden raittiina pysymisen onnistumista.

Although excessive ethanol consumption is a major cause of health problems throughout the Western world, the detection of excessive alcohol consumption by laboratory methods continues to lack sensitivity and specificity. Increasing evidence is currently available to indicate that carbohydrate-deficient transferrin (CDT) is a useful marker for assessing potentially harmful alcohol consumption, but due to heterogeneity in the methods available for its measurement, conflicting views have been available on the validity of CDT assays for detecting alcohol abuse. It has also been suggested recently that diagnostic improvements may be achieved by combining CDT and γ-GT measurements into a marker defined as γ-CDT. In addition, serum sialic acid (SA) has been proposed as a new marker of alcohol consumption. Little research has yet been carried out into the clinical value of such measurements, however.

In this work various CDT assays, SA and the conventional laboratory markers of ethanol consumption (γ-GT, AST and MCV) are compared in the context of the assessment and follow-up of alcoholics with or without liver disease determined by combined clinical, laboratory and morphological indices. The controls were healthy volunteers who were either social drinkers or abstainers, without any history of hazardous drinking. A new approach for defining a combined γ-CDT marker of ethanol abuse was also developed using data obtained from Axis %CDT turbidimetric assays. The data obtained from the CDT assays were compared with a wide variety of conventional laboratory markers and serum sialic acid determinations. The %CDT method, which excludes the trisialotransferrin isoform from the measurement, showed equal or better sensitivity and higher specificity in detecting hazardous drinking than CDTect, which has been the most widely used assay for measuring CDT during last decade. The differences were especially clear when the patients diagnosed were women. Both of these methods showed higher sensitivities than the old %CDT-TIA method that reacts to the trisialotransferrin fraction of serum transferrin. ROC analyses showed the highest diagnostic accuracies to be achieved with g-GT, CDT and SA measurements, while self-reported alcohol consumption over a period of one month prior to admission had closest correlations with the %CDT and SA results. The presence of liver pathology was reflected in the results of CDTect, γ-GT, AST and PIIINP, a marker of fibrogenesis, whereas the %CDT method and SA were less sensitive in this respect. The combined γ-%CDT method exceeded the diagnost! ic accuracy of all the markers, was less dependent on liver status, and showed the highest correlation with self-reported alcohol consumption. During follow-up with supervised abstinence the mean %CDT values were found to show a slower rate of normalization than CDT values measured with the CDTect method.

The new %CDT method appears to have advantages over previous versions of CDT methods, and its improved characteristics may be most useful in assays for excessive alcohol consumption in female alcoholics, patients with liver disease and patients with abnormal serum transferrin concentrations. While CDT and γ-GT appear to achieve the highest overall accuracy in the detection of problem drinking, serum sialic acid and PIIINP measurements may possess additional value, particularly when there is a need to differentiate between the effects of alcoholic liver disease and ethanol drinking per se. The data also indicate that the new γ-%CDT method yields improved diagnostic accuracy for the detection of excessive ethanol consumption. The present findings may prove to be of value when assessing alcohol markers for use in monitoring abstinence.