Family Practice, San Gregorio Health Care Centre and
1 Internal Medicine, Doctor Negrín General Hospital, Las Palmas, Spain
Received 24 March 2000; in revised form 23 August 2000; accepted 29 December 2000
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ABSTRACT |
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INTRODUCTION |
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Blood markers, in contrast to other diagnostic tests, could provide objective criteria for alcohol misuse because they can be applied in patients who may be unwittingly underestimating their own alcohol intake or in patients unable to respond, in some cases secondarily to injury.
An ideal marker must possess certain characteristics. It should possess a high sensitivity and specificity and not be modified by certain traits of individual patients. Its detection should not be dependent on temporal sampling and it should correlate well with the amount of alcohol consumed. The ideal marker should be easily measured with a rather simple and low-cost technique (Rosman and Lieber, 1992). To date, no marker is known to fulfil all these requirements, although the recently studied marker carbohydrate-deficient transferrin (CDT) has raised expectations.
The aim of this project was to assess the diagnostic usefulness of CDT for detecting ARP in the hospital setting, and also to evaluate the influence that gender and age may have on it and to compare this value to that of other screening measures, such as other biological markers and the CAGE questionnaire.
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PATIENTS AND METHODS |
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For an estimated prevalence of 20% (Bruguera et al., 1994), the sample size was calculated to achieve a sensitivity of 85%, at a precision level of 7% and 95% confidence interval. Thus 99 eligible patients were sampled consecutively. All these patients fulfilled ICD-10 criteria for harmful alcohol consumption or alcoholic dependence (World Health Organization, 1992
) and would have been consuming alcohol during the month prior to the admission so as to be considered hazardous drinkers by The Royal College of Physicians of London (1987) (i.e. 168 g per week of alcohol for males and 120 for females). A total of 80 control subjects were randomly selected and matched to the study group for age and gender. They met none of the above criteria. Ex-drinkers were not excluded from the control group. Exclusion criteria were patients under 15 years of age and those suffering from any mental disorder that precluded the completion of our questionnaire.
Data reporting weekly alcohol intake, as that referred to the 2 weeks prior to hospital admission, were collected from the history using the Standard Drink Unit (SDU) system for quantification purposes by applying the equivalence proposed by The Royal College of Physicians of London (1981) (i.e. 1 SDU = 8 g of alcohol). Afterwards CAGE was administered, since it is the most widely used questionnaire (Ewing, 1984), marking the cut-off value at two positive answers. Also the eventual presence of hepatic damage was considered, being that defined by clinical findings suggesting portal hypertension, biochemistry (i.e. liver function tests and serology) or ultrasonography data. Finally, a blood sample was obtained within the 48 h following hospital admission to determine CDT,
-glutamyltransferase (GGT), mean corpuscular volume (MCV), aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase, platelets, triglycerides and uric acid levels. CDT was determined with a Cobas-MiraPlus instrument based on column chromatography through an immunological technique using Axis biological reactants from Norway. The test accorded with internal as well as external consistency. Positive values were considered beyond 5%.
Diagnostic usefulness for detecting ARP was determined for CDT, conventional biological markers and CAGE, as well as the influence that gender and age could have on it. As for the latter, three age categories were established (40, 4159 and
60 years old). We also evaluated the relationship between biochemical markers and CAGE with the amount of alcohol consumed weekly, as well as that of classical biological measures with CDT. Statistical analysis was performed using Statistical Package for Social Sciences (SPSS) 8.0 version for Windows and Tabulated Data Epidemiological Analysis (EPIDAT) 2.1 version for Windows. Sensitivity, specificity, overall value, positive and negative predictive values and likelihood ratios and the area under the receiver operating characteristic (ROC) curve were calculated to assess the diagnostic usefulness.
2-Test (for quantitative variables), Student's t-test and MannWhitney test (for qualitative and quantitative variables of normal and non-normal distribution respectively), Pearson and Spearman rank correlation coefficients (quantitative variables of normal and non-normal distribution respectively) were used for univariant analysis. Level of statistical significance was set at 5%.
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RESULTS |
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Among those patients with alcohol disorders, 66 (67%) had concurrent liver disease (94% alcoholic type and 6% viral type), whereas in the control group only 20 (25%) exhibited some form of liver disease (30% viral type, 25% alcoholic type, 10% fatty liver and 35% other types).
No patient refused to collaborate in data collection. Average weekly SDU consumption by patients with ARP was 102.6 ± 107.3 whereas for the control group it was 4.3 ± 6.5. Measures of central tendency and dispersion for gender and age are as shown in Table 1. A positive result for CAGE was found in 77 (78%) patients with ARP (95% CI: 68.185.3) and in one control patient (1%).
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Univariant analysis
Analysis of the relationship between alcohol intake, biological markers and CAGE revealed a statistically significant positive correlation between average SDU weekly intake and CDT values (P < 0.001), GGT (P < 0.001), MCV (P < 0.001), AST (P < 0.001), ALT (P < 0.017), CAGE (P < 0.001) and a negative correlation with platelet count (P < 0.015) (Table 4). Analysis of this relationship in the group of patients with alcohol disorders only showed positive and significant correlations between SDU weekly intake and CDT levels (P = 0.044), AST (P = 0.048) and CAGE (P < 0.001).
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DISCUSSION |
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Our results agree with most published studies indicating that the sensitivity of CDT determination decreases in women (Anton an Moak, 1994; Gronbaek et al., 1995; Yersin et al., 1995
; Huseby et al., 1997
). This difference has been attributed to gender-specific consumption patterns, as well as lower physiological testosterone level and/or the relative increase in oestrogens in this group (Yersin et al., 1995
). Studies evaluating the age effect showed no coherent results (Yersin et al., 1995
; Huseby et al., 1997
).
Nor does unanimity exist when assessing the diagnostic usefulness of CDT in the presence of liver disease (Ouyahya et al., 1995; Radosavljevic et al., 1995
; Nalpas et al., 1997
) or, particularly, the alcoholic type (Meregalli et al., 1995
; Rublo et al., 1997
; Henriksen et al., 1997
). Niemela et al. (1995) showed that CDT increases during the first stages of hepatic damage, and a negative correlation was seen between CDT values and the morphologic severity index. In our present study, we observed significantly higher levels in the liver dysfunction group of patients, perhaps due to the fact that most of them were carriers of a mild to moderate degree of hepatic disease. Given that ex-drinkers with current non-hazardous consumption were not excluded from the control group, among this latter group, some cases of alcoholic liver disease could eventually be found. Concerning these and steatosis cases, we cannot have absolute certainty about the absence of current harmful consumption. Although it might have been interesting, we did not assess the differences among each of the liver disease groups, in view of the small numbers of subjects. As expected, we found a positive correlation between CDT values and the amount of alcohol intake, as much in the whole group of patients as in the group of patients with alcohol disorders solely, showing a coefficient similar to those reported by Niemela et al. (1995).
In the present study, the diagnostic usefulness of CDT did not exceed that of some classical markers such as GGT or MCV. The results reported in the literature are still controversial (Bell et al., 1994; Stauer et al., 1995
; Yersin et al., 1995
; Huseby et al., 1997
). While investigating CDT in combination with GGT we did not find, contrary to some authors (Randell et al., 1998
), any greater effectiveness, while sensitivity increased up to 93% and specificity decreased to 39%. Therefore biological markers would constitute a useful diagnostic tool for patients denying or underestimating their alcohol consumption and for those not available for interview. Thus, we can conclude that CDT is an effective diagnostic measure to detect ARP, its effectiveness not exceeding that of conventional biological markers.
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ACKNOWLEDGEMENTS |
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FOOTNOTES |
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REFERENCES |
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