Department of Laboratory Medicine and Medical Research Unit, Seinäjoki Central Hospital, and University of Tampere, FIN-60220 Seinäjoki, Finland
* Author to whom correspondence should be addressed at: Tel.: +358 6 415 4719; Fax: +358 6 415 4924; E-mail: onni.niemela{at}epshp.fi
(Received 2 June 2005; first review notified 15 July 2005; accepted in final revised form 8 August 2005)
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ABSTRACT |
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INTRODUCTION |
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Over the past decades, both the total ethanol consumption per capita and associated medical disorders have continued to increase. Simultaneously, the percentage of individuals fully abstaining from ethanol has decreased. In previous studies and in routine health care, reference intervals for GT determinations have been based on values obtained from mixed populations of apparently healthy moderate drinkers and abstainers, whereas only limited attention has been paid on the exact amounts of ethanol consumption in these individuals.
In this work we explored the relationship between ethanol consumption and GT values in individuals with a wide variety of ethanol consumption. Our data indicate distinct effects of mild to moderate ethanol consumption on serum GT levels, which should be considered in the clinical use of GT measurements as a marker of ethanol abuse and liver status.
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METHODS |
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Ethical considerations
The procedure was approved by the institutional review board. Informed consent was obtained from the participants and the study was carried out according to the provisions of the Declaration of Helsinki.
Statistical methods
Values are expressed as mean ± SD. Comparisons were made with Kruskal-Wallis test and Dunn's Multiple Comparison Test or MannWhitney test when comparing two groups. Correlations were calculated with Pearson productmoment correlation coefficients. Reference intervals were calculated after logarithmic transformation as previously described (Horn and Pesce, 2003). A P-value <0.05 was considered statistically significant.
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RESULTS |
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DISCUSSION |
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Studies in the past have shown that a number of biochemical parameters are altered in alcoholics, of which serum GT has emerged as one of the most efficient tests (Bagrel et al., 1979; Chick et al., 1981
; Papoz et al., 1981
; Bernadt et al., 1982
; Leino et al., 1995
; Anttila et al., 2004
). The present study indicates that even moderate amounts of ethanol consumption influence serum GT concentrations at population level and this phenomenon may significantly affect the interpretation and the establishment of common reference intervals for GT measurements in health care. The data support the view that in order to improve the diagnostic potential of laboratory markers of excessive ethanol consumption and liver status, the reference intervals of each test should be based on healthy individuals who abstain from ethanol. Since a gold standard for a bona fide social drinker currently does not exist, the concepts of moderate drinking and social drinking should also be defined more accurately and the proportions of abstainers and moderate drinkers considered separately when selecting reference individuals in future studies.
The present data indicate that the estimated upper normal limits for GT measurements would be 40% higher if the data based on moderate drinkers would be used as the basis of the reference population instead of abstainers. In accordance with this view, a recent NORIP survey from the Nordic countries showed markedly increased GT reference values (Stromme et al., 2004
). The diagnostic sensitivity of GT measurements as a marker of excessive ethanol consumption would obviously improve if reference intervals would be based on the data from abstainers. This work indicates that 13% of alcoholics would escape detection if moderate drinkers are used as the reference population, instead of abstainers. Thus, there may be a need for revising the reference range downwards. It may, however, be argued that setting a lower limit could worsen the specificity of GT assays and lead to a high number of false positive values. According to this work,
11% of the moderate drinkers would have shown increased values. However, there may be individuals who are in the upper range of the limits of social drinking. Since the data are based on self-reports, we cannot rule out occult alcohol abuse in these subjects. It should be noted, however, that future studies are clearly warranted to explore the independent effect of various possible sources of unspecificity on GT values, such as obesity or diabetes in individuals reporting either moderate drinking or no drinking. Our preliminary analyses on moderate drinkers with different degrees of obesity have indicated potentiation of GT activities in individuals with significant obesity (data not shown). The associations between GT, moderate drinking, and obesity have previously been examined by Kornhuber et al. (1989)
who also concluded that the definition of GT normal values may need to be readdressed. The correlation (r = 0.35) between alcohol consumption per se and GT values in this study is consistent with previous observations (Bagrel et al., 1979
; Chick et al., 1981
; Papoz et al., 1981
; Leino et al., 1995
; Anttila et al., 2004
). The correlation was, however, essentially similar in women (r = 0.36) and men (r = 0.32), though some earlier studies have reported higher correlations in populations consisting of men only (Papoz et al., 1981
; Anton and Moak, 1994
; Sillanaukee et al., 1998
). The diagnostic sensitivity of GT has usually been shown to be lower for women than for men (Anton and Moak, 1994
; Yersin et al., 1995
; Mundle et al., 2000
). Based on the present data, these findings may in part be explained by the definition of reference intervals. Furthermore, GT values in women may increase at lower levels of alcohol consumption as a result of women's increased vulnerability to the toxic effects of alcohol (Anton et al., 1998
).
The advent of carbohydrate-deficient transferrin (CDT) testing has recently imposed a new challenge to the use of GT measurements because CDT has shown higher specificities than GT in several trials. Although CDT has become an increasingly important tool for assessing excessive ethanol consumption, it appears that CDT and GT frequently increase in different individuals (Anton et al., 2002; Anttila et al., 2003
; Neumann and Spies, 2003
). Some studies have concluded that GT is more efficient in identifying female alcoholics than CDT (Anton and Moak, 1994
, Anton et al., 2002
). Therefore, it seems at this time that CDT alone does not cover all the needs for an alcohol marker in routine clinical practice, and other markers, especially GT are needed as well.
Taken together, the present data indicate that the changes in drinking behaviour at population level may parallel increases in recommended GT cut-offs, which may subsequently lead to problems in recognizing excessive alcohol consumption in its early phase. Therefore, a critical re-evaluation of reference intervals even in the use of the well-established biochemical markers of alcohol consumption may be necessary in order to improve the assessment and treatment of patients with early-stage alcohol problems.
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ACKNOWLEDGEMENTS |
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