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Objectives and Methods: Carbohydrate-deficient transferrin has been proposed as a marker of alcohol consumption. The aim of this study was to evaluate the accuracy of the carbohydrate-deficient transferrin serum level, measured by ion exchange chromatography followed by radioimmunoassay (Kit CDTect), for the diagnosis of excessive alcohol intake in patients with liver diseases. Ninety-four patients (68 men, 26 women, age 21-71 years), 42 with alcoholic liver diseases and 52 with non-alcoholic liver diseases, were studied. Twenty-six patients consumed > or = 40 g alcohol per day (mean alcohol intake: 84 +/- 52 g per day) and were considered to be excessive drinkers., Results: The sensitivity of carbohydrate-deficient transferrin for the diagnosis of excessive alcohol intake was 35%, and the specificity was 91%. By pairing carbohydrate-deficient transferrin with other markers of alcohol consumption, the sensitivity of the association of carbohydrate-deficient transferrin and gammaglutamyl transpeptidase was 96%, and the specificity was 59%., Conclusion: In patients with liver diseases, carbohydrate-deficient transferrin is a specific marker of excessive alcohol intake but a lack of sensitivity may limit its use.

The correct clinical interpretation of any laboratory marker requires a good knowledge of its positive and negative predictive values, which are calculated from the sensitivity and the specificity of the test and from the prevalence of the disease. This means that we need a good assay technique in the case of biochemical tests, and a well defined reference sample (control subjects), with the ability to distinguish between a diseased and a healthy subject. In the field of alcohol abuse markers, each of these notions presents some degree of difficulty. There is no perfect solution, and a compromise has to be agreed upon.

Microheterogeneity of serum transferrin as well as erythrocyte membrane sialic acid content were examined in alcoholic patients and healthy controls. Both the sialic acid content of erythrocyte membranes and of the circulating transferrin were significantly lower in alcoholic patients than in controls. A moderate daily ethanol intake (less than 80 g) allowed to observe a proportional relationship between alcohol intake and the carbohydrate deficient forms of transferrin, and also a correlation between alcohol intake and the membrane sialic acid content. This supports the hypothesis of ubiquitary alterations of glycosylations in connection to ethanol intoxication. Additional disturbances could explain the absence of correlations between membrane sialic acid, pattern of abnormal forms of serum transferrin, and alcohol intake in heavy alcoholic patients.

It has been known for some years that a partial deglycosylation of transferrin occurs in the sera of alcohol abusers. Different methods have been proposed in order to evaluate this carbohydrate-deficient fraction of serum transferrin. Chromatofocusing or isoelectric focusing followed by direct immunofixation have been used until now. Recently, a new method called the carbohydrate-deficient transferrin (CDT) test based on ion-exchange chromatography has been developed by Stibler et al. (Alcohol Clin Exp Res 10:535-544, 1986). Here we compare this new method with results obtained using our Tf index determination method. The upper limit of normal values was set to the 90th percentile of the values observed in a reference population. The population under investigation consisted of 50 healthy volunteers and 160 alcohol abusers whose ethanol consumption was evaluated through a questionnaire. Sensitivity and specificity of the CDT test have been found higher than 0.76 and 0.90, respectively. The correlation between both methods was 0.794, a satisfactory result considering that the CDT test and the Tf index do not exactly measure the same part of the carbohydrate-deficient transferrin. In a population of 23 patients with liver diseases not related to alcohol abuse, no abnormal CDT value was observed. We can conclude from these results that the CDT test now seems to be the best test to detect alcohol abusers.

In order to study a possible modification, secondary to alcohol consumption, of the distribution of various molecular forms of transferrin, we have compared its total serum concentration with that of several fractions in reference groups and excessive drinkers. The study was conducted in 50 patients; 35 drinkers admitted for detoxication, and 15 in the control group. The percentage of transferrin focalizing at pH 5.7 (Tf 5.7) is significantly higher in drinkers while the transferrin concentration is almost unchanged. During the weaning period, we observed a significant decrease of Tf 5.7 in two weeks. This parameter seems to be extremely sensitive regarding alcohol consumption; its specificity should be evaluated before coming to the conclusion that it present a definite advantage in the screening of excessive drinkers.

The gammaGT of a generally healthy population is abnormally high due to the presence of ethanol in the diet. We confirm Rosalki's finding that a high proportion of alchoholics show an increased gammaGT activity. After alcohol deprivation, the gammaGT of alcoholics decreases in the first few days according to an exponential law with a half-time of return to normal of 5-17 days. Among past alcoholics, those who stopped drinking for a year have a lower GT activity (mean: 21 mU/ml) than a generally healthy population and in the range of Szasz's reference values. Alcoholics who did not stop drinking have a higher gammaGT activity (mean: 172). Ascitic cirrhotics who drink at least 1 liter of wine per day have also a high activity (mean: 139) while those who stopped drinking for at least 2 months have a much lower activity (mean: 49) and those who stopped for a year a normal activity. In 10 out of 11 alcoholic cirrhotics who stopped drinking, the gammaGT decreased (half-time: 11-54 days). These results show that the determination of gammaGT activity is a good test for the detection of ethanol impregnation.

384 hospitalized patients of both sexes were classified into drinkers and non-drinkers according to clinical criteria. On admission, we measured four blood parameters : glutamate dehydrogenase, gamma glutamyl transferase, aspartate aminotransferase and the mean corpuscular volume. the discriminating power of these laboratory parameters was evaluated by descriptive statistical tests and by the determination of their positive and negative predictive value. Glutamate dehydrogenase appears to present a sensitivity almost equivalent to that of gamma glutamyl transferase and a better specificity : this results in a more positive predictive value. The two other laboratory parameters are less discriminating.

We developed a method for the quantification of the different fractions of serum transferrin, based on an isoelectric focusing followed by immunofixation. We employed this technique to study whether or not the pattern of the serum transferrin was altered in the serum of drinkers. We established an increase of the fraction that focused at 5.7 (Tf5.7) and a concomittant decrease of the fraction that focused at 5.4 (Tf5.4) in the sera of drinkers. The separation between drinkers and controls was enhanced when using the ratio Tf5.7/Tf5.4, called Tf index. The predictive value of this test was 0.88, which means that 88% of the subjects were correctly classified as heavy drinkers or not.

The conceptual foundation and structural development of a major secondary prevention program established in France to screen, diagnose and treat persons in the prodromal stages of alcoholism are described. Also discussed are the application and validity of a simple examination procedure used to identify alcoholics in this program.

The aim of this study was to assess the performance of the transferrin (Tf) index in screening heavy drinkers and to compare its performance to that of gamma glutamyl transpeptidase (GGT). Tf index, GGT, and transaminase activities were determined in a group of 173 subjects (49% males) recruited in a family doctor's practice (age: 54 +/- 1.5 yr; daily alcohol intake: 32 +/- 3.5 g; mean +/- SEM). Tf subfractions were quantified by isoelectric focusing and immunofixation on polyacrylamide gel. The Tf pl 5.7 to 5.4 ratio, or Tf index, was used as a marker of excessive drinking, with a cut-off point at 7%. Alcohol consumption was assessed through a face-to-face interview. Excessive drinkers were defined as those with a daily alcohol intake greater than 80 g over at least 2 years; 20 were classified as excessive drinkers (alcohol consumption: 92-232 g/day). All but four had normal transaminase activities indicating the low prevalence of hepatic impairments in this sample. The Tf index was found to have a sensitivity of 45%, specificity 89%, positive predictive value 35%, negative predictive value 92%. The corresponding results for GGT were 52%, 80%, 27%, and 92%, respectively. Concordance between the Tf index and GGT was assessed by the kappa coefficient (kappa) which was 0.22 indicating poor agreement between the two markers in selecting excessive drinkers (perfect association: kappa = 1, no association: kappa = 0).

An epidemiological survey was carried out in France in 1982-3 to study the proportions of occasional and chronic drinkers among people injured in accidents of all kinds. The characteristics of 4796 victims recruited in the emergency units of 21 hospitals were recorded. Systematic blood sampling was performed to determine the blood alcohol concentration and two markers of chronic alcohol consumption--gamma-glutamyltransferase activity and mean corpuscular volume. Alcohol was present in the blood of 35% of the injured people, with concentrations exceeding 17.4 mmol/l (0.8 g/l) in one man out of four and in one woman out of 10. gamma-Glutamyltransferase values and mean corpuscular volume were also much higher than in a reference population of healthy subjects, indicating that most of the intoxicated subjects were probably chronic drinkers. This was confirmed by a discriminant analysis which showed an overall proportion of 30% of chronic drinkers among casualties. In France, therefore, the policy for preventing accidents should focus on chronic as much as on occasional drinking.

We present a study of 107 in-patients of a detoxification center. As expected, 81 percent of them showed upon admittance an increased serum gamma glutamyl transferase (GGT). After alcohol withdrawal, GGT decreased in all but one of these patients. More surprisingly, even among the rest of the patients exhibiting upon admittance a GGT result within the reference range, there still occurred a significant decrease in 50 percent of the cases. Thus, whether the initial GGT is high or normal, we observed a decrease in 96 patients out of 107, i.e., a sensitivity of 0.90. The decrease test consists in asking a subject to refrain from any alcohol intake during a short period, e.g., seven days. If any significant diminution of serum GGT occurs, the possibility of alcohol abuse should at least be given serious consideration before being rejected. This test was used up to now only when GGT was initially high. The present results show that it can be attempted even when GGT is initially within the normal range, with a sensitivity of 0.90.

The routine detection of chronic alcoholism is necessary during any medical examination whether private or in hospital, or in occupational medicine. The practitionner now has available a simple reliable and cheap test. It consists of the serum estimation of gamma-glutamyl-transferase (gammaGT) and interpretation of the average red cell volume supplied by automatic counting of the red cell. Out of 120 chronic alcoholic subjects ; 67% has a gammaGT increased and 44% had macrocytosis. Under the influence of weaning, there was a rapid fall in gammaGT and a slower reduction in average red cell volume. gammaGT estimation was thus a more sensitive test than M.C.V. for the detection of chronic alcoholics and the control of withdrawal. Its association with the rise in immunoglobulin A-transferrin ratio which we have suggested permits the detection of almost all chronic alcoholics in the population studied.

Different molecular forms of transferrin (Tf) have been separated in sera from alcoholics and controls by isoelectric focusing on ultrathin polyacrylamide gels using a semi narrow pH range. The main fraction focused at pH 5.4 (Tf5.4) and minor components appeared among controls at pH 5.7 (Tf5.7). This fraction was increased among alcoholics and was sometimes accompanied by a fraction focusing at pH 5.9 (Tf5.9). Fractions were quantified by densitometry following immunofixation. Significant differences in the ratios Tf5.4/Tf and Tf5.7/Tf between the groups were obtained, but no difference could be determined in the total Tf. We used the ratio Tf5.7/Tf5.4 called Tf index to distinguish alcoholics from controls. The sensitivity, the specificity and the global predictive value of this test were 0.82, 1 and 0.88 respectively. These results seems to indicate that the Tf index is more reliable for the detection of alcohol abuse than liver enzymes such as gammaglutamyl transferase (gamma GT) or glutamate dehydrogenase (GDH).

53 percent of ethanol drinkers had, before detoxication, a gamma-GT higher than the upper limit of the reference interval at the 2.5 percent risk level (36 mU/ml). 44 percent had a mean corpuscular volume (MCV) higher than the limit (99.2 mum3). In alcoholics not previously "weaned" during a rest cure or in a hospital the proportion becomes 67 percent for gamma-GT but remains at 44 percent for MCV. gamma-GT thus seems a better test for the screening of an excessive ethanol intake than MCV, especially when the subject has not been previously weaned.

The behavior of serum glutamate dehydrogenase after alcohol withdrawal was studied in 64 alcoholics admitted to a detoxification center. The enzyme activity decreased in 57 patients by a median of -35.8 percent in 24 h. Thus, the decrease of serum glutamate dehydrogenase after 24 h of ethanol abstinence can serve as a test of alcohol abuse.