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ABSTRACT: Excessive alcohol consumption is associated with the generation of antibodies against neoantigens induced by ethanol metabolism. However, the associations between such immune responses, ethanol consumption, and liver injury remain unclear.
Eight-six male alcoholics with (n=54) or without (n=32) liver disease, and 20 male volunteers (6 abstainers, 14 moderate drinkers) underwent clinical, morphological, and biochemical assessments of liver status and ethanol consumption.
Antiacetaldehyde adduct IgAs in both groups of alcoholics were significantly higher than those in the controls. Elevated IgGs occurred in patients with liver disease, whereas IgMs were high in the heavy drinkers without apparent liver disease. Liver disease patients had high levels of both proinflammatory (IL-2, IL-6, IL-8, TNF-alpha) and antiinflammatory (IL-10) cytokines, whereas those without liver disease showed elevated IL-6, IL-8, and IL-10 only. Ethanol consumption correlated significantly with antiadduct IgA and IL-6 levels, which also showed parallel changes upon abstinence.
Alcoholic liver disease is associated with the generation of IgAs and IgGs against acetaldehyde-derived antigens and enhanced levels of both pro- and antiinflammatory cytokines, whereas elevated IgA, IL-6, and IL-10 characterize alcoholics without liver disease. These data suggest that immunological mechanisms may play a role in the sequence of events leading to liver disease in some patients with excessive drinking.
The American Journal of Gastroenterology 07/2005; 100(6):1303-10. · 7.28 Impact Factor
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ABSTRACT: The detection of excessive alcohol consumption by laboratory methods continues to lack sensitivity and specificity. Recent studies have suggested that diagnostic improvement may be achieved by combining carbohydrate-deficient transferrin (CDT) and gamma-glutamyltransferase (GT) measurements into a marker defined as gamma-CDT.
We developed a new approach for determining gamma-CDT by using the data obtained from the Axis %CDT turbidimetric assays. Marker results were compared in the assessment of 65 alcoholics, who were either with (n=34) or without (n=31) liver disease, as analysed by clinical, laboratory, and morphological criteria. Reference individuals were 45 healthy volunteers who were either social drinkers or abstainers.
Gamma-GT and CDT results derived from both CDTect and %CDT measurements were used to calculate marker ratios as follows 0.8 x ln(GT)+1.3 x ln(CDT). With the established cut-off of 4.0 for the gamma-%CDT, the sensitivity of this method was 94% for men and 82% for women, as compared to 61% and 46% for %CDT and 70% and 73% for GT. The gamma-%CDT method was less dependent on liver status than the various other markers and showed the highest correlation with self-reported alcohol consumption (r=0.7254).
The data indicates that the new gamma-%CDT method yields improved diagnostic accuracy for the detection of excessive ethanol consumption.
Clinica Chimica Acta 01/2004; 338(1-2):45-51. · 2.54 Impact Factor
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ABSTRACT: Due to methodological heterogeneity, conflicting views have been expressed on the validity of CDT measurements in the detection of alcohol misuse.
We compared the characteristics of the conventional CDTect method and the Axis turbidimetric CDT assays in the assessment of 62 alcoholics, who were either with (n = 33) or without (n = 29) liver disease, as analysed by combined clinical, laboratory, and morphological indices. Controls were 45 healthy volunteers who were either social drinkers or abstainers.
In the total sample of alcoholics, the sensitivity of the %CDT method, which excludes the trisialotransferrin isoform from the measurement, was 63% for men and 46% for women, as compared to 65% and 36% of CDTect, respectively. Both of these methods showed higher sensitivities than the %CDT-TIA method, which reacts with trisialotransferrin (32% and 25%, respectively). The assay specificities were 100% for men and 91% for women with %CDT, and 96% and 87% with the CDTect, respectively. The correlation between the CDTect and %CDT method was higher in men (r = 0.86) than in women (r = 0.57). The presence of liver disease was found to influence the results of the CDTect method, such that the highest CDT concentrations were observed in patients with mild to moderate liver disease, especially among women, whereas the %CDT method was less sensitive to the effect of liver pathology. The self-reported alcohol consumption from the 4 weeks prior to sampling showed a higher correlation between the %CDT results (r = 0.64, P < 0.0001) than with the CDTect results (r = 0.40; P < 0.01).
The data indicate that the new %CDT method offers advantages over the previous versions of the CDT methods. The improved characteristics may be most useful in assays for excessive alcohol consumption in female alcoholics, patients with liver disease, and in patients with abnormal serum transferrin concentrations.
Alcohol and Alcoholism 38(5):415-20. · 2.95 Impact Factor
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ABSTRACT: There are only limited data comparing the diagnostic characteristics of carbohydrate-deficient transferrin (CDT) measurements in assays for excessive alcohol consumption under controlled conditions.
We compared different CDT assays and the conventional laboratory markers of ethanol consumption, gamma-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.
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).
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.
Alcohol and Alcoholism 39(1):59-63. · 2.95 Impact Factor
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ABSTRACT: Background: The detection of excessive alcohol consumption by laboratory methods continues to lack sensitivity and specificity. Recent studies have suggested that diagnostic improvement may be achieved by combining carbohydrate-deficient transferrin (CDT) and gamma-glutamyltransferase (GT) measurements into a marker defined as γ-CDT. Methods: We developed a new approach for determining γ-CDT by using the data obtained from the Axis %CDT turbidimetric assays. Marker results were compared in the assessment of 65 alcoholics, who were either with (n=34) or without (n=31) liver disease, as analysed by clinical, laboratory, and morphological criteria. Reference individuals were 45 healthy volunteers who were either social drinkers or abstainers. Results: Gamma-GT and CDT results derived from both CDTect and %CDT measurements were used to calculate marker ratios as follows 0.8×ln(GT)+1.3×ln(CDT). With the established cut-off of 4.0 for the γ-%CDT, the sensitivity of this method was 94% for men and 82% for women, as compared to 61% and 46% for %CDT and 70% and 73% for GT. The γ-%CDT method was less dependent on liver status than the various other markers and showed the highest correlation with self-reported alcohol consumption (r=0.7254). Conclusions: The data indicates that the new γ-%CDT method yields improved diagnostic accuracy for the detection of excessive ethanol consumption.
Clinica Chimica Acta.
