New Alcohol Markers—How Useful Are They in Population Studies: The Svalbard Study 1988–89

Regular high consumption of alcohol in selected populations have, with high precision, been identified by two new alcohol markers; carbohydrate-deficient transferrin and mitochondrial aspartate aminotransferase. To test these markers in an unselected population, gamma-glutamyltransferase (GGT), carbohydrate-deficient transferrin (CDT), and mitochondrial aspartate aminotransferase (mAST) were measured in the Norwegian population, 310 males and 171 females, aged 18 to 60 years, living at Svalbard. Using self-reported alcohol intake as gold standard, sensitivity, specificity, positive predictive value, and likelihood-ratio were estimated according to different cutoff-points for alcohol intake and for the tests. In contrast to earlier studies, the sensitivity was in general low. With a specificity of 90% or higher, the sensitivity did not exceed 26% for any of the tests. Whereas CDT showed its best discriminatory power at lower intake of alcohol, GGT discriminated best at higher levels. Parallel and serial analysis of CDT and GGT indicated a conditional independence between the tests, as well as at higher and at lower levels of alcohol consumption. mAST was judged as not suitable in population studies.     

Effect of type of alcoholic beverages on carbohydrate-deficient transferrin,sialic acid,and liver enzymes

BACKGROUND: There are only limited data obtained under well controlled conditions on the effects of moderate drinking on markers of alcohol use disorders. The aim of this study was to investigate the effects of moderate intake of different alcoholic beverages on these markers, including carbohydrate-deficient transferrin (CDT), sialic acid (SA), and the liver enzymes gamma-glutamyltransferase, aspartate aminotransferase, and alanine aminotransferase. METHODS: Eleven apparently healthy, nonsmoking middle-aged men were included in a 12-week randomized, diet-controlled crossover trial according to a 4 x 4 Latin-square design. Changes in CDT, SA, gamma-glutamyltransferase, aspartate aminotransferase, and alanine aminotransferase were analyzed after 3 weeks of daily intake of four glasses (40 g of alcohol) of red wine, beer, spirits (Dutch gin), or water (control). RESULTS: After 3 weeks' daily consumption of red wine, a significant decrease of serum CDT concentration was observed compared with water consumption. There was no effect of any alcoholic beverage on the other outcome measures. CONCLUSIONS: Daily consumption of 40 g of alcohol from different types of alcoholic beverages with dinner did not affect SA or liver enzymes. Further investigations to explore the mechanisms for the red wine-induced decreases of CDT, including changes in iron metabolism, are clearly needed.     

Sialic Acid: New Potential Marker of Alcohol Abuse

BACKGROUND: A number of laboratory markers are suggested for the detection and monitoring of alcohol abuse. However, there is still a need to find better indicators of alcohol abuse. Sialic acid (SA) is the name for a series of acyl-derivatives of neuraminic acids that occur as nonreducing terminal residues of glycoproteins or glycolipids in biological fluids and cell membranes. In this study, we investigated the diagnostic value of SA as a marker of alcohol abuse. METHODS: Sera from social drinkers (n = 38) and alcoholics (n = 77) were analyzed for sialic acid by a colorimetric assay and for carbohydrate-deficient transferrin (CDT) by a radioimmunoassay method. Mean corpuscular volume (MCV), gamma-glutamyltransferase (GGT), aspartate aminotransferase (ASAT), and alanine aminotransferase (ALAT) were determined by using routine methods. RESULTS: The sialic acid levels of both female and male subjects were significantly (p < 0.001) increased among alcoholic subjects when compared with social drinkers. SA levels were decreased after 3 weeks of treatment. The sensitivity and specificity for SA, respectively, were 57.7 and 95.5 for women and 47.8 and 81.3 for men. The respective values for CDT were 57.7 and 95.5 for women and 78.3 and 100.0 for men; for GGT, 60.0 and 95.5 for women and 60.9 and 87.5 for men; for MCV, 52.4 and 95.5 for women and 47.8 and 100.0 for men; for ASAT, 53.8 and 95.5 for women and 43.5 and 100.0 for men; and for ALAT, 38.5 and 90.9 for women and 39.1 and 87.5 for men. Among women, SA and GGT, and among men CDT, showed the largest area under receiver operation curve. CONCLUSION: This study indicated that sialic acid levels were elevated by high alcohol consumption and reduced during abstinence, especially among women. Thus, sialic acid seems to be an interesting marker that needs further evaluation as a diagnostic tool for alcohol abuse.     

Changes in Carbohydrate-Deficient Transferrin Levels after Alcohol Withdrawal

Sequential serum levels of carbohydrate-deficient transferrin (CDT) were determined in 72 alcoholics at various intervals during detoxification. Before treatment, 57 patients (79%) had increased CDT values (Group A), whereas in 15 individuals (21%) (Group B), CDT levels were within the normal range. In 51 Group A patients, CDT decreased progressively after cessation of alcohol intake (half-life, 16 +/- 5 days), but fluctuated and remained abnormal in the remaining six. Nine Group B patients maintained normal CDT values throughout the follow-up period, but slightly or moderately increased levels were recorded on one occasion in the other six Group B subjects. Patients whose CDT levels had reached normal values after treatment, showed a recurrent increase in CDT after a relapse. gamma-Glutamyl transferase activities, which were elevated in 56% of Group A and in 80% of Group B alcoholics, showed a decrease after cessation of alcohol consumption in most patients with initially elevated values (Group A, 30 of 32; Group B, 10 of 12). Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities, as well as mean corpuscular volumes (MCV) were normal in the majority of patients. CDT/total transferrin ratios correlated positively with CDT levels. CDT proved to be the most sensitive marker for chronic alcoholism (79%), whereas GGT activity levels were more useful only in patients with normal CDT levels before alcohol withdrawal. In the assessment of treatment outcome, the combination of CDT and GGT as markers yielded a sensitivity of 95%.     

Carbohydrate-deficient transferrin (CDT) and HDL cholesterol (HDL) are highly correlated in male alcohol dependent patients

BACKGROUND: Serum levels of total HDL cholesterol (HDL) are reportedly influenced by recent alcohol intake. We examined the correlation between HDL cholesterol and widely used markers of excessive alcohol intake, such as carbohydrate-deficient transferrin (CDT), gamma-glutamyl-transferase (GGT), or mean corpuscular volume of erythrocytes (MCV), of which CDT is thought to be the most specific. METHODS: Several serological markers [i.e., CDT, GGT, aspartate aminotransferase (ASAT), alanine aminotransferase (ALAT), MCV, and HDL] were determined in 100 actively drinking male patients with alcohol dependence (DSM-IV) and in 27 non-alcohol-dependent controls, according to routine procedures. Spearman's rank correlation coefficients were calculated. RESULTS: We found a highly significant positive correlation between HDL and CDT (r(s) = 0.55; p < 0.0005) in patients, but not in controls (r(s) = 0.13;p = 0.51). HDL was also positively correlated with GGT, ALAT, ASAT, and MCV only in patients. CONCLUSIONS: HDL cholesterol, as a widely determined parameter, may represent a useful routine marker for recent excessive alcohol intake. High HDL cholesterol levels should alert clinicians to investigate a patient's recent pattern of alcohol consumption.     

Carbohydrate-Deficient Transferrin as a Marker of Alcohol Consumption in Male Patients with Liver Disease

Carbohydrate-deficient transferrin (CDT) has been proposed as a marker of alcohol abuse. However, its value in patients with associated liver disease is still controversial. The aim of the study was to investigate the usefulness of CDT as a marker of alcohol consumption in patients with liver disease. We measured serum levels of CDT and those of commonly used hematological and biochemical markers, mean corpuscular volume (MCV), transaminases (AST and ALT), and γ-glutamyltransferase in 179 male subjects divided into four groups: 45 active drinkers (13 with normal liver, 21 with fibrosteatosis, and 11 with liver cirrhosis), 45 abstinent chronic alcoholics (18 with and 27 without liver disease), 58 patients with nonalcoholic liver disease, and 31 healthy controls. Serum CDT in active alcoholics was 37.5 ± 3.6 units/liter, being significantly higher than that of abstinent alcoholics (20.3 ± 1.5 units/liter), patients with nonalcoholic liver disease (18.1 ± 1.1 units/liter), and controls (13.1 ± 0.8 units/liter). Contrary to the other markers, no significant differences were observed in CDT values in relation with the presence and severity of liver disease in either the active drinkers or in the abstinent alcoholics. The sensitivity and specificity of CDT as a marker of alcoholism in the series as a whole was 64% and 82%, respectively, similar to the best conventional marker, MCV (64 and 82%). In patients with liver disease, CDT maintained good sensitivity (72%) and specificity (83%). Receiver operating characteristic analysis confirmed that CDT had a similar diagnostic value to that of MCV, but better than γ-glutamyltransferase and transaminases for the detection of alcohol abusers. The good diagnostic efficacy of CDT remained unchanged when analyzing only patients with liver disease. We conclude that serum CDT is a good marker of alcoholism and is less influenced than the currently used biochemical markers for associated liver disease. Thus, CDT is an effective laboratory test to detect alcohol abuse regardless of the presence of alcoholic liver disease.     

Identification of elevated carbohydrate-deficient transferrin (CDT) serum level as transferrin (Tf)-D-variant by means of isoelectric focusing

Many studies have shown carbohydrate-deficient transferrin (CDT) to be a sensitive and specific marker of chronic alcohol abuse. We present the case of a 23-year-old, healthy professional soccer player who caused a car accident due to alcohol consumption. Several CDT test results were elevated above the laboratory reference range and were considered to be caused by alcohol intake at a level commensurate with misuse and thus license reapplication was refused. In addition, assuming chronic alcohol abuse, the young man suffered from increasing social isolation. He was finally referred to our out-patient clinic for further evaluation on the assumption of a liver disease. Since chronic alcohol consumption was denied, and there was no evidence of liver disease, a qualitative characterization of the transferrin isoforms was performed. Isoelectric focusing of serum transferrin revealed a pattern atypical for chronic alcohol intake but detected a genetically determined transferrin (Tf)-D-variant. The changed amino acid sequence caused an overlapping of transferrin isoforms with different degrees of sialylation, thus revealing false-positive serum CDT values. Determination of this Tf-D-variant heterozygosity resulted in his social rehabilitation and license reinstatement. Thus, where the evidence for alcohol dependency is either uncertain or uncorroborated, qualitative isoelectric focusing of transferrin is a useful method for analyzing unexplained CDT elevations, thus increasing the value of CDT as a marker for chronic alcoholic abuse.     

Carbohydrate-Deficient Transferrin and Conventional Alcohol Markers as Indicators for Brief Intervention among Heavy Drinkers in Primary Health Care

Brief intervention is a promising treatment for heavy drinking. The present study examined the diagnostic value of carbohydrate-deficient transferrin (CDT), mean corpuscular volume (MCV), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and γ glutamyltransferase (GGT) in detecting early-phase heavy drinkers for brief intervention treatment in primary health care. Laboratory data were collected from consecutive 20- to 60-year-old, early-phase heavy drinkers (329 males and 136 females), who were willing to undergo brief intervention treatment in five primary health care outpatient clinics. An elevated value of at least 1 of the 5 markers studied was found in 75% of the male and in 76% of the female heavy drinkers. The sensitivities of CDT, MCV, AST, ALT and GGT values were low; in men, respectively, 39%, 28%, 12%, 28%, and 33%. and in women 29%, 40%, 20%, 29%, and 34%. However, marker combinations, including CDT, reached a good level of sensitivity; the best triple combination (CDT or MCV or GGT) was positive in 69% of the men and 70% of the women. According to logistic regression, the age of the patient had an increasing effect on MCV, ALT and GGT. High body mass index increased all transaminases and decreased CDT and MCV. Smoking increased MCV and decreased AST. Thus, primary health care marker combinations, especially those including CDT, should be considered for the detection of early-phase heavy drinkers for brief intervention treatment.     

Urinary ethyl glucuronide as a novel screening tool in patients pre- and post-liver transplantation improves detection of alcohol consumption

Optimal selection of liver transplant candidates and early detection of alcohol relapse after orthotopic liver transplantation (OLT) is necessary to improve long-term outcomes. In this study, urinary ethyl glucuronide (uEtG) was prospectively evaluated as a novel screening tool for alcohol detection in the transplant setting. Overall, 141 liver transplant candidates and recipients, visiting the outpatient clinic for a total of 308 times, were included. At each visit, the alcohol markers, uEtG, ethanol, methanol, and carbohydrate-deficient transferrin (CDT), as well as the state markers, alanine transaminase, aspartate transaminase, gamma glutamyl transpeptidase (GGT), and mean corpuscular volume (MCV), were determined, then compared to patients' self-reports on alcohol intake. Urinary EtG significantly increased the detection rate of alcohol consumption, compared to the other alcohol markers (P < 0.001). In 93% of patients and at 92.5% of visits with positive alcohol markers, alcohol intake was detected by uEtG and/or CDT. Sensitivity and specificity of uEtG were 89.3% and 98.9% and of CDT were 25% and 98.6%, respectively. Urinary EtG was the best independent predictor of alcohol consumption in univariate and multivariate analysis (positive predictive value: 89.3%; negative predictive value: 98.9%; odds ratio: 761.1; P < 0.001). It showed a superior prediction rate, when compared to established alcohol and state markers, as well as to the combination of CDT with MCV and GGT, assessed by net reclassification improvement (NRI) (NRI: 1.01, P < 0.001; NRI: 1.755, P < 0.001). CONCLUSION: uEtG is a sensitive, specific, and reliable marker for the detection of recent alcohol intake pre- and post-OLT. In combination with CDT, uEtG should be considered as a tool for routine alcohol screening within the transplant setting.     

Sex differences of carbohydrate-deficient transferrin, gamma-glutamyltransferase, and mean corpuscular volume in alcohol-dependent patients

BACKGROUND: Biological markers like carbohydrate-deficient transferrin (CDT), gamma-glutamyltransferase (GGT), and mean corpuscular volume (MCV) are used widely to screen for alcoholism. Most research has focused on male alcoholics, and there are few studies on female patients. The results are inconsistent; in general, they show lower sensitivities for all markers for women. METHODS: We compared the diagnostic value of CDT, GGT, and MCV in 126 alcohol-dependent patients (91 men, 35 women) who entered an inpatient treatment program. For the receiver operating characteristic (ROC) analyses, we investigated a control group of 112 patients (64 men, 38 women) from the Department of Psychiatry at the University of Tübingen with no diagnosis of substance abuse or substance dependency. RESULTS: Mean levels of CDT and MCV were significantly different in male and female patients. CDT showed higher test results in men (4.4% vs. 2.8%, p < 0.05), whereas mean levels of MCV were higher in women (99.7 fl vs. 96.4 fl,p < 0.01). The sensitivities of CDT and GGT were higher in men than in women (CDT: 76% vs. 54%,p < 0.1; GGT: 68% vs. 43%,p < 0.05), and the sensitivity of MCV was significantly higher in women (71% vs. 41%,p < 0.01). The superiority of MCV in women also was supported by ROC analyses (p < 0.01). The combined use of markers showed satisfactory sensitivity rates of > or = 80% not only in men but also in women. Yet, the specificity rates were partly below the recommended 90% for identifying alcohol abuse; therefore, these markers must be combined with caution. CONCLUSIONS: If combined, the biological markers CDT and GGT are useful diagnostic instruments for both alcohol-dependent men and women. According to our results, the "forgotten" marker MCV is superior in women and is a marker of second choice in men. The combination GGT and MCV is the most cost-effective choice for men and women.     

Usefulness of Carbohydrate-Deficient Transferrin in Alcoholic Patients with Normal γ-Glutamyltranspeptidase

The biological diagnosis of alcoholism is conducted routinely by assay of γ-glutamyltranspeptidase (GGT) and mean corpuscular volume (MCV). However, their low specificity and sensitivity have prompted research to find other more reliable parameters. Stibler showed an increase in desialylated transferrin [carbohydrate-deficient transferrin (CDT)] in alcoholic patients. The normal value of the serum CDT concentration is under 60 mg/liter; a value between 60 and 100 mg/liter indicates probable alcoholism, and a value >100 mg/liter indicates a very high probability of alcoholism (specificity: 99%). Its sensitivity ranges from 60 to 91%, and its specificity ranges from 92 to 100%. Its half-life is 17 ± 4 days. CDT is thus a useful laboratory marker, but its assay is costlier and more complex than that of GGT. This study concerns 31 alcohol-dependent patients as defined by DSM-IV, with GGT levels in the normal range. It evaluates CDT at day 0 and its time course after 15 days withdrawal. GGT and MCV were assayed concomitantly. Remarkably, the results show a sensitivity of 83.9 (26 positives of 31) in this particular population and a specificity of 92.2. The fall in CDT after 15 days withdrawal was 36%. CDT is thus a particularly useful marker for the diagnosis and follow-up of alcoholics with normal GGT levels.     

Carbohydrate-deficient Transferrin, a Marker for Chronic Alcohol Consumption in Different Ethnic Populations

Serum levels of carbohydrate-deficient transferrin (CDT) were determined in a racially mixed population of 107 alcoholics, 18 healthy, nonalcoholic control subjects, 62 abstinent alcoholics, and in 64 Caucasian patients with various nonalcoholic liver diseases. The upper limit of normal CDT levels was 80 mg/liter (2 SD above the mean). CDT values exceeding this level were found in more than 80% of Black, Puerto Rican, and Caucasian alcoholics who had consumed greater than or equal to 50 g of alcohol/day for 1 month or longer prior to testing. Puerto Rican alcoholics had higher CDT values than the Black and Caucasian ethnic groups; however, these differences were significant only when compared to the Black population. Of 64 patients with nonalcoholic liver diseases, one individual with chronic active hepatitis (CAH) with an alcohol consumption of 20 g/day, and 10 of 26 subjects with primary biliary cirrhoses (PBC), who claimed to consume either no or only occasional moderate amounts of alcohol, had CDT levels ranging from 81 to 144 mg/liter. Seven of these individuals were in advanced stages of PBC. Total transferrin levels were variable and not significantly different in all subject groups studied. CDT/total transferrin ratios were increased in most patients with abnormal amounts of CDT, and there was a significant correlation between these ratios and CDT levels in all study groups. Serum enzyme parameters as well as red blood cell mean corpuscular volumes did not correlate with CDT values.(ABSTRACT TRUNCATED AT 250 WORDS)     

Evaluation of Carbohydrate-deficient Transferrin Compared with Tf Index and Other Markers of Alcohol Abuse

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.     

A comparative study between carbohydrate-deficient transferrin and gamma-glutamyltransferase for the diagnosis of excessive drinking in a liver unit

Aims: To compare the efficacy of carbohydrate-deficient transferrin and gamma-glutamyltransferase for the diagnosis of excessive alcohol intake in patients admitted in a liver unit.Methods: The 346 patients were divided into three groups of alcoholics: 57 patients (31 men, 26 women) with a normal liver, 77 patients (51 men, 26 women) with non-cirrhotic alcoholic liver disease, and 61 patients (43 men, 18 women) with alcoholic cirrhosis; and three groups of non-alcoholics: 35 abstainers (21 men, 14 women), and 58 healthy blood donors (26 men, 32 women), and 58 patients (32 men, 26 women) who had a non-alcoholic liver disease. Carbohydrate-deficient transferrin and gamma-glutamyltransferase were measured at admission using commercially available kits.Results: Carbohydrate-deficient transferrin was more sensitive than gamma-glutamyltransferase in patients without alcoholic liver disease, in both men (85 vs 54%) and women (64 vs 36%). Carbohydrate-deficient transferrin sensitivity decreased slightly but not sigficantly according to the severity of the liver disease in men and women. The sensitivity of gamma-glutamyltransferase which was low in men and women without alcoholic liver disease, improved in groups with moderate or severe alcoholic liver disease: not less than 80% in men and up to 100% in women. The specificity of carbohydrate-deficient transferrin in patients with non-alcoholic liver disease was consistently higher than that of gamma-glutamyltransferase (80% vs 60%).Conclusions: In liver units, carbohydrate-deficient transferrin can help to identify excessive drinkers without liver disease with a higher efficacy than that of gamma-glutamyltransferase; carbohydrate-deficient transferrin can also be used to distinguish between alcoholics with moderate liver disease and patients with non-alcoholic liver diseases.     

Screening for concomitant alcohol abuse in schizophrenia: clinical significance of the Munich Alcoholism Test and laboratory tests.

For the early and correct diagnosis of the comorbidity of schizophrenia and alcoholism, a valid laboratory marker would be most helpful in clinical practice. Seventy schizophrenics admitted to a general psychiatric unit of an urban hospital located in a large industrial area in Germany prospectively underwent a detailed addiction history, the Munich Alcoholism Test (MALT) and determinations of serum gamma-glutamyltransferase (gammaGT) and carbohydrate-deficient transferrin (CDT). Cutoff levels for laboratory tests represented the 95th percentile of data obtained from 100 matched healthy controls. Using the MALT, we found evidence of concomitant alcohol consumption in 42.8% of the study patients. The sensitivities of gammaGT and CDT for detecting alcohol abuse (confirmed using DSM III-R criteria) were 70.6 and 58.8%, respectively. Our data suggest that the MALT can be used as a reliable screening test for alcohol use in schizophrenia. In neuroleptic-treated schizophrenics with pathological gammaGT, but low MALT scores, the corresponding CDT may serve as a highly specific marker to verify a concomitant alcohol abuse.     

Preoperative evaluation of chronic alcoholics assessed for surgery of the upper digestive tract

BACKGROUND: Alcoholics are at risk of developing major complications in the postoperative period. Adequate prophylactic treatment, as well as preoperative abstinence, can significantly decrease the rate of complications. However, the preoperative diagnosis of alcoholism is difficult to establish. The purpose of this study was to assess whether three preoperative visits, an alcohol-related questionnaire (CAGE), and the laboratory markers carbohydrate-deficient transferrin (CDT) and gamma-glutamyltransferase (GGT) would increase the rate of detection of chronic alcoholics. METHODS: The study included the Departments of ENT, Facial and Maxillofacial Surgery, and General Surgery of a university hospital; 705 male patients were assessed for tumor surgery of the upper digestive tract and were allocated to 5 different groups. All patients were seen three times, and five different strategies were used to detect chronic alcoholics. The gold standard was the diagnosis of alcohol misuse made by an experienced (blinded) investigator according to the DSM-III-R. The main outcome measurements were the detection rates of the different test strategies. RESULTS: By clinical routine alone, only 16% were detected during the first visit and 34% after three visits. If the CAGE questionnaire was added, sensitivity increased to 64%. The further addition of GGT or CDT led to 80 and 85% detections, respectively. A combination of all tests had a sensitivity of 91%. CONCLUSIONS: To detect more alcoholic patients at risk for major complications, patients should be seen more often, and additional diagnostic tools such as the CAGE, CDT, and GGT should be used before surgery.     

The effect of iron overload and iron reductive treatment on the serum concentration of carbohydrate-deficient transferrin

Summary. The concentration of carbohydrate-deficient transferrin in serum (CDT) has been used as a reliable indicator of recent alcohol consumption. We have investigated the utility of this laboratory test in 20 patients with hereditary haemochromatosis (HH) by simultaneous evaluation of serum concentrations of liver transaminases, γ-glutamyl transpeptidase, iron, transferrin and asessment of the liver iron concentration by magnetic resonance imaging. 11 patients were re-examined during iron depletion with phelebotomies. In all 11 patients intensive but not maintenance iron removal was associated with an increase in serum CDT, in three patients even to levels above the reference range. The mean serum CDT increased from 8.5 (SD 2.2) U/1 to 16.6 (SD 7.2) U/1 (P < 0.001). Iron mobilization from the liver was found particularly responsible for the increase in serum CDT. Independent of this finding we found a significant semi-logarithmic correlation (r =−0.77. P = 0.009) between the MRI determined liver iron depletion. Our findings indicate that the utility of serum CDT as a measure of alcohol consumption in patients with HH may be compromised, especially during intensive iron depletion.     

Carbohydrate-Deficient Transferrin as a Measure of Immoderate Drinking: Remaining Issues

A growing body of investigations demonstrate that elevated levels of carbohydrate-deficient transferrin (CDT) effectively distinguishes alcoholics recently consuming large amounts of alcohol from light social drinkers or teetotalers. Nevertheless, important questions still remain concerning the value of CDT as a more generalized marker of alcohol consumption. Most important, the nature of the drinking pattern, including quantity and frequency, necessary to raise levels of CDT significantly remains unclear. Neither has research convincingly demonstrated that CDT is as accurate a marker for women, young adults, or non-Caucasian ethnic groups as for White, middleaged men.
Whereas CDT might serve as a useful outcome measure in trials of alcoholism treatment effectiveness, current research suggests that CDT is of limited value in identifying problematic drinking in general medical or community settings in which a broad continuum of drinkers is represented. Combining CDT with other biochemical or self-report screening measures may, however, improve sensitivity in these contexts.
At present, the most accurate laboratory technique to detect CDT seems to be isoelectric focusing. Additional research, however, is needed to resolve the issue of whether CDT is best quantitated as a simple value or if its ratio to total transferrin or non-CDT results in higher predictive validity.     

Comparing the Diagnostic Accuracy of Carbohydrate-Deficient Transferrin, γ-Glutamyltransferase, and Mean Cell Volume in a General Practice Population

In certain populations, the biological alcohol marker carbohydrate-deficient transferrin (CDT) is known to have a high diagnostic accuracy. The aim of this study was to compare the diagnostic accuracy of CDT, gamma-glutamyltransferase (gamma-GT), and mean cell volume (MCV) in a general practice population; more specifically, to ascertain whether CDT is a better tool than gamma-GT and MCV for (early) recognition of excessive alcohol use. To represent the general practice situation as realistically as possible, three different drinking patterns are defined: irregular excessive, regular excessive, and very excessive. From a sample of 524 men from seven general practices, sensitivity, specificity, and predictive values of the three markers for the three drinking patterns were compared, and receiver-operating characteristic analysis was used to compare differences between the markers. The results indicate that drinking patterns do influence the (difference in) diagnostic accuracy. CDT has a higher diagnostic accuracy for all three drinking patterns than gamma-GT and higher predictive values for hazardous [(ir)regular excessive] drinking patterns than MCV. However, receiver-operating characteristic analyses failed to demonstrate a significant difference between these patterns. It is concluded that the performance of all tests is too low to be useful for screening procedures in a general population; however, some tests may be useful for case finding. CDT seems to be the best alcohol marker available, although the difference between CDT and MCV is small.     

The effect of total body water on the relationship between alcohol consumption and carbohydrate-deficient transferrin

BACKGROUND: Clinicians agree that alcoholism commonly is overlooked in their patients, and that treating the symptoms without directing therapy to the underlying cause at best delays an inevitable decline in the patient's general health and well-being. The current analysis focused on carbohydrate-deficient transferrin (CDT), a promising biological marker of dangerous alcohol consumption. METHODS: Included in our study were men (730) and women (613) from study sites in Canada, Brazil, and Japan. All subjects were participants in the WHO/ISBRA Study on State and Trait Markers of Alcoholism, who completed an extensive demographic, medical, and behavioral survey and provided blood samples for determination of CDT levels. ANOVA and chi2 test for equality were used to examine the effect of total body water (TBW) on the alcohol consumption/CDT relationship. To examine whether accounting for differences in TBW improved the diagnostic properties of CDT when used as a state marker for alcohol consumption, odds ratios were calculated for men and women separately. RESULTS: Our results show that accounting for individual differences in TBW significantly influenced the alcohol consumption/CDT dose-response relationship. The effect of TBW was different for men compared with women. When we used a consumption cutoff value of 40 g/day and the CDTect recommended cutoffs (20 for men; 27 for women), adjusting for differences in TBW significantly increased diagnostic performance of CDT in men but not women. CONCLUSIONS: The dependence of CDT measures on body water content needs to be taken into account to maximize the performance of CDT as an effective state marker of alcohol consumption in males.