Conventional tests for alcoholism fail to confirm hazardous and harmful alcohol use (HHAU) accurately and objectively. We validated a Bayesian Alcoholism Test (BAT) for confirming the diagnosis of HHAU.

BAT is based on studies on the prevalence of HHAU and other diseases causing similar abnormalities, and on conditional probabilities of these disorders and associated biochemical markers and clinical signs. BAT was compared to carbohydrate-deficient transferrin (CDT) and gamma-glutamyltransferase (GGT) in treatment-seeking alcoholics, non-treatment-seeking heavy drinkers, and controls. Main outcome measures were test sensitivity and specificity, likelihood ratios, and receiver-operating characteristic (ROC) curves.

Comparing alcoholics and controls, sensitivity of BAT (94%) was significantly higher than CDT (63%) and GGT (73%). The area under the ROC curve for BAT (.989) was significantly higher than the area under the curve for CDT (.909) and area under the curve for GGT (.902). Using pooled data of all 182 subjects included in the study, the amount of drinking had a significant better correlation coefficient with BAT (.795) than with CDT (.657), and GGT (.604).

BAT has better diagnostic properties than CDT and GGT for confirming HHAU.

To test the clinical performance of carbohydrate-deficient transferrin (%CDT), gamma-glutamyltransferase (gamma-GT) and mean corpuscular erythrocyte volume (MCV) as biomarkers for alcoholism with a special focus on patients suffering from liver diseases.

Well-characterized collectives of alcohol-dependent patients with current consumption (ALC patients, n = 101), and relevant control groups (115 social drinkers, 46 patients with unspecifically increased gamma-GT, 51 hepatitis patients and 20/31 patients with non-alcohol/alcohol-dependent liver cirrhosis) were included into the study. The Positive Alcohol Use Disorders Test (AUDIT) score, International Classification of Diseases version 10 (ICD-10)/Diagnostic and Statistical Manual version IV (DSM-IV) criteria and blood drawn within 4 days of last drinking were inclusion criteria for subjects with regular heavy drinking. %CDT was determined using an automated assay which recently had been completely modified.

Median AUDIT scores of patients without/with regular heavy drinking were 1-3/27. The following medians/95th percentiles were obtained for %CDT: social drinkers 2.2/3.0, patients with unspecifically increased gamma-GT 2.1/3.0, hepatitis 2.0/4.4, non-alcohol-dependent liver cirrhosis 2.4/4.8, alcohol-dependent liver cirrhosis 3.0/5.9, ALC patients 3.9/14.9. Differences between patients without and with alcohol abuse were highly significant (P < 0.001). No differences in CDT values were found between males and females. There was no correlation between %CDT values, gamma-GT, MCV and the amount of alcohol consumed in ALC patients; 3.0%CDT (95th percentile social drinkers) is proposed as cut-off for the test used (Tina-quant %CDT 2nd-generation). At this cut-off, the sensitivity for ALC patients was 73.3%, whereas gamma-GT/MCV had a sensitivity of 71.3%/64.4%. Multivariate analysis performed at 95% specificity resulted in an improvement of the sensitivity by combining %CDT with gamma-GT (83.2%). A further enhancement of the sensitivity to 88.1% was obtained by combination of %CDT, gamma-GT and MCV. The diagnostic specificity of %CDT calculated at the cut-off of 3% was 93.5% in patients with unspecifically increased gamma-GT, 88.2% in hepatitis patients and 70.0% in patients with non-alcohol-dependent liver cirrhosis. %CDT was more specific in these patient collectives than MCV, and especially more than gamma-GT (specificity in hepatitis 52.9%, and 35.0% in non-alcohol-dependent liver cirrhosis).

%CDT is of high diagnostic value to support diagnosis of alcohol-use disorders. The specificity of this marker in patient groups with liver disorders is superior to the biomarkers gamma-GT and MCV.

Carbohydrate-deficient transferrin (CDT) is a biomarker for chronic alcohol intake of more than 60 g ethanol/d. It has been reported to be superior to conventional markers like gamma-glutamyltransferase (GGT) and mean corpuscular volume MCV). This review covers theoretical and analytical aspects, with data from controlled drinking experiments and from different population subgroups such as subjects with different liver diseases or different drinking patterns. CDT determinations are particularly indicated in (1) cases of chronic alcohol consumption and relapses after withdrawal, (2) license reapplication after driving under alcohol influence, (3) differentiating patients with enzyme-inducing medication from those with alcohol abuse, 4) congenital disorders of glycosylation such as carbohydrate-deficient glycoprotein syndrome Ia (CDGS Ia), and (5) patients treated for galactosemia. The main advantage of CDT is its high specificity, as evidenced in combination with increased alcohol consumption. CDT values are not markedly influenced by medication except in immunosuppressed patients, who may show low CDT values. In general, CDT values appear less elevated after alcohol intake in women. The main disadvantage is the relatively low sensitivity. Hence, this parameter is not suitable for screening for subjects with alcohol abuse in the general population. As CDT, GGT, and MCV are connected with chronic alcohol consumption by different pathophysiological mechanisms, a combination of these parameters will further improve the diagnostic value.

Biomedical markers may provide additive objective information in screening and confirmation of acute or recent consumption, intoxication, relapse, heavy drinking, hazardous/harmful use/abuse and dependence and alcohol use related organ dysfunction (alcohol use-related disorders: AUDs).

To review the use of biomarkers in clinical practice to detect AUDs.

About one-fifth of the patients seen in clinical practice have AUDs, which offer a variety of treatment options if diagnosed. The diagnosis of AUDs relies on clinical and alcohol-related history, physical examination, questionnaires and laboratory values. No clinical available laboratory test [e.g. for acute abuse: alcohol in blood or breath; for chronic alcohol abuse: gamma-glutamyl transferase (GGT), mean corpuscular volume (MCV), carbohydrate-deficient transferrin (CDT)] is reliable enough on its own to support a diagnosis of alcohol dependence, harmful use or abuse. Sensitivities, specificities and the predictive values may vary considerably according to patient and control group characteristics (e.g. gender, age or related comorbidity). In patient groups with limited cooperation markers may be helpful when considering treatment options.

More research is needed to determine the value of markers (single or combined, with questionnaires) in the context of clinical decision-making algorithms in defined settings and with defined dichotomous outcome variables.

The role of alcohol misuse in the genesis of seizures is probably often undetected. The aim was to investigate the utility of carbohydrate deficient transferrin (CDT) compared with other biomarkers and clinical examination in the diagnosis of alcohol related seizures.

The study included consecutively 158 seizure patients-83 men and 75 women-with mean age 45 (16-79) years. Seizures related to alcohol use were identified by a score > or =8 in the alcohol use disorders identification test (AUDIT positive). AUDIT was applied as the gold standard to which sensitivity and specificity of the various markers were related. Blood samples were obtained from 150 patients on admission and analysed for ethanol, liver enzymes, and CDT, using AXIS Biochemicals' %CDT-TIA kit.

53 patients (34%) were AUDIT positive. Using the commonly applied decision value for %CDT of 5.0%, a sensitivity of 41% and a specificity of 84% were obtained. Analysis of receiver operator characteristics (ROC) curves disclosed an optimal cut off value for %CDT of 5.4%, which yielded a sensitivity of 39% and a specificity of 88%. At a specificity of 80%, the sensitivity was 43% for %CDT and 26% for GGT. The %CDT sensitivity was markedly higher for men than for women. Compared with GGT, ASAT, ALAT, and ASAT/ALAT ratio, CDT was the best single biomarker for alcohol related seizures. However, even in the subgroup of withdrawal seizures, the sensitivity level barely exceeded 50%. Clinicians scored alcohol as the main cause of the seizure in only 19 cases (12%). In 38 (24%) cases, clinicians suspected that alcohol had a role (sensitivity of 62% at a specificity of 89%). Their ability to identify AUDIT positive patients was better than that of any biomarker, but many cases were missed. Agreement of clinicians' scores to CDT was only fair (kappa=0.28). CDT concentrations were significantly increased among alcohol abstaining patients on enzyme-inducing antiepileptic drugs. Six out of 16 patients with false positive CDT results were exposed to such drugs.

CDT is not recommended as a stand alone marker for alcohol related seizures, but may provide a useful contribution to the overall diagnostic investigation of seizures. Confirmatory studies are needed as to the apparent vulnerability of CDT to antiepileptic drugs.

Deaths from the effects of alcohol intoxication are encountered routinely in forensic practice. In an important number of cases difficulty may arise in interpreting the significance of results obtained in the autopsy. In clinical practice biochemical markers, particularly serum gamma-glutamyl-transpeptidase (GGT), alanine aminotransferase (ALT), aspartate transaminase (AST), carbohydrate-deficient transferrin (CDT), and erythrocyte mean corpuscular volume are used to diagnose heavy alcohol consumption. CDT is used as a reliable and specific marker. In postmortem diagnosis, because of the difficulty in interpreting blood alcohol levels and relatively non-specific pathological features, biochemical compounds have been studied for use as possible markers. The aim of this study was to evaluate the usefulness of the postmortem determination of CDT in vitreous humor as a confirmation of antemortem alcoholism. CDT levels were studied in 66 male cadavers with a mean age of 55.9 years (S.D. 17.0, range 22-87 years) with a mean postmortem interval of 17.9 h (S.D. 11.4, range 4-72 h). Cases were assigned to two diagnostic groups according to the antemortem diagnosis of alcoholism. Statistically significant differences were found for CDT and ALT concentrations between the two diagnostic groups. The highest vitreous humor levels of CDT and ALT were obtained in the group of cases with a previous diagnosis of alcoholism. Our results suggest that vitreous humor CDT levels are useful in cases where the postmortem diagnosis of alcoholism is hindered by the non-specificity of data.

Seric carbohydrate-deficient transferrin (CDT) is a biochemical marker of chronic alcohol abuse. Assessment of the influence of factors likely to modify CDT concentration is necessary to justify its use in the analysis of post-mortem blood samples. Hemolysis, site of collection and storage were tested. Hemolysed samples showed decreased CDT concentration. Statistical analysis of CDT concentration in cardiac blood versus femoral blood revealed no significant differences. Storage for fifteen days at +4 degrees C or +20 degrees C did not affect CDT concentration but repeated freezing and thawing resulted in decreased levels of CDT.

This is a systematic review of the studies in which carbohydrate-deficient transferrin (CDT) has been compared to other laboratory markers in different experimental conditions, clinical settings, and populations. Only the studies (n = 54) in which CDT was compared either to the conventional or new biological markers of alcoholism, heavy drinking, or alcohol use were selected for further evaluation. Two prospective studies indicate that in men CDT is slightly more sensitive than gamma-GT in reflecting changes in these markers caused by drinking of a moderate and fixed amount of alcohol during three to four weeks. In one prospective study, in which the drinking history of male heavy drinking volunteers was as close the golden standard as possible; that is, obtained by a prospective anonymous drinking diary, CDT was slightly but not significantly better marker than conventional laboratory markers (ASAT, ALAT, gamma-GT and beta-Hex) in the identification of men drinking more than 400 g of alcohol daily. Similar prospective studies concerning women have not been done. Six prospective treatment outcome studies indicate that CDT may be a significantly more sensitive marker than gamma-glutamyltransferase (gamma-GT) in the detection of relapses in male alcoholics. However, these two tests can also be considered to be complementary markers. Furthermore, in the detection of relapses the baseline values of CDT and gamma-GT should be measured and compared on individual basis to the pretreatment values. Comparable data are not available from female alcoholics. In selective materials comprising male alcoholics and heavy drinkers, CDT was found to be a slightly more sensitive marker than gamma-GT in seven retrospective studies. In five studies, gamma-GT was slightly better. However, the differences between CDT and gamma-GT in general were not statistically significant. In three studies, the combined use of CDT and gamma-GT improved the sensitivity but with the expense of specificity. Only four studies included women and in three of these the sensitivity of gamma-GT was better than that of CDT, whereas in one study CDT was better than gamma-GT in the detection of female heavy drinkers. Seven studies performed in primary health care settings and among young populations demonstrate that the performance of CDT in the identification of heavy and problem drinkers in this type of populations is very low, although comparable to the poor performance of the conventional laboratory markers, too. According to seven studies, the sensitivity of gamma-GT is slightly better than that of CDT in the identification of excessive alcohol consumption among hospitalized male and female patients. However, in this type of hospital setting, the specificity of CDT is markedly higher than that of gamma-GT. There is some evidence indicating that the performance of the tests can be improved with the combined use of both tests. Eight studies indicate that both in men and women CDT is a better marker than gamma-GT in the identification of alcohol abuse among patients with alcoholic and nonalcoholic liver diseases. This is mostly due to the higher specificity of CDT as compared to that of gamma-GT.

Carbohydrate-deficient transferrin (CDT), a microheterogeneous form of serum transferrin (Tf), has been proposed as the most reliable marker of chronic alcohol consumption, although unexplained false-positive and -negative results have been reported. We investigated whether body iron influenced CDT serum levels by studying alcohol abusers with or without iron overload and nonabusers with iron deficiency or iron overload caused by genetic hemochromatosis (GH). In alcohol abusers, CDT was significantly lower in the presence of iron overload than in the absence (24.6 +/- 16.5 U/L vs. 33.3 +/- 11.7 U/L; P <.01), with false-negative results almost exclusively in patients with iron overload. Similarly, in nonabusers with GH, CDT was lower than in normal controls (9.6 +/- 2. 2 U/L vs. 15.7 +/- 3.3 U/L; P <.0001), whereas, patients with iron deficiency anemia had significantly higher levels than controls (28. 1 +/- 5.8 U/L vs. 15.7 +/- 3.3 U/L; P <.0001). In nonabusers, iron supplementation therapy significantly decreased CDT levels in patients with iron deficiency anemia (33.7 +/- 6.6 U/L vs. 21.7 +/- 5.2 U/L; P =.0007), while iron-depletion treatment significantly increased CDT levels in patients with GH (9.7 +/- 2.0 U/L vs. 14.7 +/- 4.0 U/L; P =.001). Alcohol abusers had a significant relationship between liver iron concentration (LIC) and the reciprocal of CDT (r =.65; P <.0001), while in nonabusers, there was a significant correlation between Tf and CDT (r =.72; P <.0001). In conclusion, CDT serum levels are markedly affected by the patient's iron status, with iron overload reducing its sensitivity in alcohol abusers and iron deficiency its specificity in nonabusers. CDT can be considered a reliable marker of alcohol abuse only when iron stores are normal.

A variety of epidemiological studies have suggested a U-shaped association between alcohol consumption and atherosclerosis progression and incidence events. Moderate intake of alcohol is considered beneficial, whereas heavy drinking increases cardiovascular disease risk.

Alcohol and cardiovascular risk-related laboratory tests were carried out in 70 consecutive male employees in connection with an occupational health survey in 1996. Carbohydrate-deficient transferrin (CDT) and gamma-glutamyltransferase (GGT) were used as markers for alcohol consumption. The subjects were divided into quartiles on the basis of CDT or GGT value.

The highest CDT quartile had significantly higher serum high-density lipoprotein (HDL)-cholesterol (P < 0.05) than the lowest quartile. The highest GGT quartile had significantly higher serum total cholesterol (P < 0. 01), lower serum HDL-cholesterol (P < 0.05), higher serum low-density lipoprotein (LDL)-cholesterol (P < 0.01) and higher serum triglyceride (P < 0.01) than the lowest quartile.

An explanation for the findings is that high alcohol consumption without significant liver induction increases the level of HDL-cholesterol, whereas high alcohol consumption with induction of liver may have adverse effects on lipoprotein metabolism. The results were interpreted to indicate that CDT and GGT detect different populations of drinkers in regard to cardiovascular lipid risk factors.

Alcoholism is one of the most frequent addictions and an important subject in forensic medicine and clinical toxicology. Several laboratory abnormalities are associated with excessive alcohol consumption. They are useful in the diagnosis of alcoholism especially during the follow-up of various treatment programs. The biological markers mostly used for diagnosis of alcoholism are presented. Especially, methods for the determination of the following diagnostic tools are reviewed: congener alcohols, gamma-glutamyltransferase, aspartate and alanine aminotransferase, beta-hexosaminidase, erythrocyte aldehyde dehydrogenase, alpha-amino-n-butyric acid to leucine ratio, macrocytosis, carbohydrate-deficient transferrin, (apo)lipoproteins, fatty acid ethyl esters, blood acetate, acetaldehyde adducts, 5-hydroxytryptophol, dolichol and condensation products. No laboratory test exists that is reliable enough for the exact diagnosis of alcoholism. The combination of physician interview, questionnaire and laboratory markers is necessary for the diagnosis of alcoholism.

Carbohydrate deficient transferrin (CDT) is now accepted as a potentially useful marker for the detection of alcohol misuse. It is not clear whether absolute values or values expressed relative to the total transferrin concentration provide the same diagnostic efficiency. CDT was measured in 35 patients with alcohol related liver disease, 35 subjects abusing alcohol without evidence of liver disease and 35 patients with chronic viral hepatitis using two commercial methods (CDTect and %CDT). To compare the methods, results were normalised by dividing the actual result by the upper limit of the reference range. Subtracting normalised %CDT results from the normalised CDTect results demonstrated a linear relationship between CDTect and total transferrin. This linear relationship could be abolished by calculating the CDTect/total transferrin ratio. The sensitivity of the methods was similar with CDTect (43 and 57%) being slightly superior to %CDT (40 and 46%). Specificity was similar (78%) for both methods. Calculation of the CDTect/total transferrin ratio improved the sensitivity and specificity slightly. The linear relationship between CDTect and total transferrin may produce misleading results in populations with a high prevalence of abnormal total transferrin concentrations and could cause difficulties in method comparisons unless taken into account.

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.

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.

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 significantly 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%).

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.

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 gamma-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 gamma-glutamyl-transferase 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.

Carbohydrate deficient transferrin has been introduced as a marker of excessive alcohol intake. The present study was undertaken in order to measure the circulating level of carbohydrate deficient transferrin in patients with alcoholic cirrhosis and to assess arteriovenous kinetics of carbohydrate deficient transferrin in liver and kidney.

The median value of serum carbohydrate deficient transferrin was 16.0 U/l in patients with alcoholic cirrhosis (n = 41), and this value was not significantly different from that of a normal control group (median 17.4 U/l, n = 55, ns). Carbohydrate deficient transferrin was significantly higher in patients with cirrhosis and high current alcohol intake than in abstaining patients (20 vs. 14 U/l, p < 0.05). Similarly, controls with a high current alcohol intake (> 50 g/day) had a significantly higher carbohydrate deficient transferrin concentration than controls with a low alcohol intake (< 10 g/day) (36 vs. 14.9 U/l, p < 0.005). No significant differences were detected between carbohydrate deficient transferrin in artery and liver vein or artery and renal vein, either in patients with alcoholic cirrhosis (n = 11) or in controls (n = 8), which indicates a slow turnover rate of carbohydrate deficient transferrin. Food ingestion did not affect the circulating level of carbohydrate deficient transferrin, and the analysis of carbohydrate deficient transferrin was almost unaffected by the presence of ethanol in plasma within the biological range (ethanol 0-100 mmol/l).

Our results suggest that measurement of carbohydrate deficient transferrin may be used in patients with alcoholic cirrhosis. High current alcohol intake is associated with higher carbohydrate deficient transferrin levels than in those with low alcohol intake, but the overlap is substantial in patients with cirrhosis. Carbohydrate deficient transferrin has a low turnover rate in both patients with cirrhosis and normals.

A new simplified method for detection and quantitation of disialontransferrin in serum is described.

The method is based on polyacrylamide gel isoelectric focusing, direct immunofixation with a specific antibody, and measurement by computerized scanning densitometry. Disialotransferrin levels were determined in 24 teetotallers and 34 alcoholics at 3 moments during detoxification. Three groups of drinkers were arranged: group 1 (without), group 2 (with light), and group 3 (with severe hepatitis).

The metho showed very good reproducibility and accuracy with a coefficient of variation between 5 to 8%. Alcoholic patients could be clearly separated from teetotallers, with a specificity of 100% and a sensitivity of 94%. After 12 days of alcohol withdrawal, disialotransferrin values declined in alcoholics but remained slightly high. They were not influenced by the severity of liver disease. No significant difference was found between the 3 groups.

An easy-to-perform, sensitive, and inexpensive method has been developed to quantify disialotransferrin that can be used by laboratories almost everywhere.

The determination of carbohydrate-deficient transferrin (CDT) in serum has been found useful as a marker of increased alcohol consumption of > 60 g/day. It is not clear why the reference range is different for women (0 to 26 units/liter) and men (0 to 20 units/liter). We evaluated serum CDT in 286 healthy subjects (209 women, 77 men) using a commercially available radioimmunoassay. Premenopausal women had higher CDT levels than postmenopausal women, whereas no age-related difference of CDT levels was found in men. In postmenopausal women, higher CDT levels were associated with estrogen replacement therapy. In premenopausal women, however, neither the phase of the menstrual cycle nor contraceptive steroid use showed a significant association with the increase in CDT levels. No significant correlations were found between CDT and either serum estradiol or serum iron. In conclusion, both premenopausal state and postmenopausal estrogen replacement therapy seem to increase serum levels of CDT. Therefore, menopausal status and exogenous estrogens should be considered when interpreting CDT values in women.

Despite a number of investigations suggesting the value of carbohydrate-deficient transferrin (CDT) as a marker of alcohol abuse, a variety of issues on the applicability of CDT measurements in clinical settings have remained unexplored. Earlier studies in this field have focused on the relationship of CDT and the amount of alcohol consumption or presence of liver disease, whereas the influence of alterations in serum transferrin concentrations on CDT has received less attention. In this study, we compared two different methods for measuring CDT (CDTect and %CDT) and total transferrin concentrations in a sample of 83 alcohol abusers (20 patients with alcoholic liver disease and 63 heavy drinkers who were devoid of liver disease, despite excessive alcohol consumption) and 89 controls, who were social drinkers or abstainers. The control population included 53 hospitalized patients with expected abnormalities in serum transferrin concentrations caused by conditions such as negative iron balance, pregnancy, or nonalcoholic liver disease. Both methods gave significantly higher values in alcohol abusers than in controls (p < 0.01), but the overall sensitivity for detecting alcohol abuse was clearly higher for CDTect (59%) than for %CDT (34%). The correlation between the results obtained by the two methods (r = 0.629) significantly improved, when the CDTect values were replaced by the ratio of CDTect/total transferrin (r = 0.770) (p < 0.05). There was a positive correlation between the CDTect and serum transferrin (r = 0.201, p < 0.01), which was significant both in the alcoholics (r = 0.240, p < 0.05), and especially in the controls (r = 0.727, p < 0.001). A significant inverse correlation emerged between %CDT and total transferrin (r = -0.302, p < 0.01). The sensitivities of CDTect and %CDT for correctly classifying alcohol abusers in the subgroup of alcoholic liver disease patients were 90% and 70% and in the subgroup of heavy drinkers without liver disease (49% and 22%), respectively. Specificities for CDTect and %CDT in this sample were 81% and 100%, respectively. However, in the subgroup of hospitalized control patients with abnormal serum transferrin, the specificity of CDTect was only 48%. According to present data, CDTect seems to be more sensitive than %CDT for detecting alcohol abuse. However, any alteration in serum total transferrin concentration markedly decreases the assay specificity. This should be considered when interpreting the assay results in patients with elevated serum transferrin, such as iron deficiency, pregnancy, or liver diseases.

Both gamma-glutamyltranspeptidase and carbohydrate-deficient transferrin have been extensively researched as biological markers of heavy alcohol consumption. The current study briefly describes each test, identifies subject variables that influence their relative sensitivities and specificities, and examines issues surrounding use of the two markers in combination. In addition, this study suggests five design features that should characterize projects evaluating the validity of biochemical markers.

Carbohydrate-deficient transferrin (CDT) measurements have been widely examined as a marker of excessive alcohol consumption, yet the information on the sensitivity of this method has remained controversial. In addition, little is known of the relationship of this marker and the severity of alcoholic liver disease (ALD). To clarify these issues, we analyzed serum samples from 373 alcohol abusers, including 200 problem drinkers with no apparent liver pathology, 173 patients with clinical or morphological evidence of ALD, and 42 healthy controls. CDT was analyzed by anion-exchange chromatography followed by radioimmunoassay. At a specificity of 100%, the sensitivity of CDT was 36% in problem drinkers reporting a mean of 710 +/- 80 (mean +/- 2SE) g of ethanol/week, as compared with the sensitivities of 44% and 35% for gamma-glutamyltranspeptidase (GGT) and mean corpuscular volume (MCV), respectively. In a subgroup of problem drinkers (n = 51) with the highest ethanol intakes (1160 +/- 180 g of ethanol/week) and severe dependence, the sensitivity of CDT increased to 64%, compared with 55% for GGT and 39% for MCV. In ALD, the CDT values were significantly higher than in the alcoholics with nonliver pathology. However, when such patients were classified according to the clinical, laboratory, and morphological severity of liver disease, CDT was found to be primarily elevated in those with the early stage of ALD, such that there was a significant negative correlation between CDT and the combined morphological index of disease severity (rs = -0.315, p < 0.05). ALD markers of fibrogenesis were elevated more frequently than CDT, showing significant positive correlations with the indices of disease severity.(ABSTRACT TRUNCATED AT 250 WORDS)

Different methods for detecting carbohydrate-deficient transferrin (CDT) were compared. In addition, their efficiency for detecting alcohol abuse among men not having clinical evidence of liver disease was studied in controls (n = 26), weekend (n = 16) and daily (n = 12) heavy drinkers, and alcoholics (n = 28). Comparisons were made between anion-exchange separation of iron-saturated transferrin (Tf) by microcolumns (CDTect) and by the Fast Protein Liquid Chromatography (FPLC% and FPLC-MG), followed by double-antibody radioimmunoassay of collected fractions. Tf fractions with pl > or = 5.7 were also measured by two different isoelectric focusing (IEF) methods, followed by immunofixation (SA-IEF-CDT and IEF-CDT-TOT), the latter method being used also for detection of asialotransferrin (IEF-CDT-AS). The cut-off was 20 units/liter for CDTect, 4.4% of total Tf for SA-IEF-CDT, and the mean +2 sd of the control group for FPLC-MG (as mg/liter of Tf), FPLC-%, IEF-CDT-TOT, and IEF-CDT-AS (all as percentage of Tf). The overall accuracies (combining sensitivity and specificity) for detecting heavy drinkers of CDTect, FPLO (mg/liter), FPLC (%), SA-IEF-CDT, IEF-CDT-TOT, and IEF-CDT-AS were 63%, 59%, 61%, 74%, 57%, and 63%, respectively; for detecting alcoholics, 87%, 83%, 81%, 89%, 37%, and 76%, respectively. In conclusion, the methods were in rather good agreement with each other. Diagnostic characteristics among heavy drinkers and correlations between methods differed slightly, probably depending on the ability of different methods to separate and detect asialo-, monosialo-, and disialotransferrin.(ABSTRACT TRUNCATED AT 250 WORDS)

An isoform of transferrin, carbohydrate-deficient transferrin (CDT) is increased in a high percentage of abusing alcoholics and has been found superior in its specificity compared with other biological markers. We used serum CDT as a screening parameter in 502 patients consecutively admitted to our medical department during a 4-week period. The intake of ethanol during the last 4 weeks was registrated by personal interviews and the mean daily consumption calculated. Serum CDT was measured at admission (CDTect) and compared with gamma-glutamyltranspeptidase (GGT), AST, ALT, and mean corpuscular volume (MCV). Serum CDT detected 18 of 26 (69%) patients who consumed > 50 g ethanol daily. The clinical sensitivity of CDT of detection ethanol consumption > 50 g daily was 69%, compared with 73%, 50%, 35%, and 52% for increased values of GGT, AST, ALT, and MCV, respectively. Altogether, 38 of 476 patients (8%) with a daily ethanol consumption < 50 g also had increased serum CDT levels. The specificity of CDT was 92%, compared with 75%, 82%, 86%, and 85% for GGT, AST, ALT, and MCV, respectively. In the 60 patients who consumed > 10 g ethanol daily, we found a significantly positive correlation between CDT and ethanol consumption (r = 0.52, p < 0.001). A positive correlation was also found between serum transferrin and CDT (r = 0.51, p < 0.001). In conclusion, the specificity of CDT is much higher compared with GGT in detecting alcohol abuse. Some acute and chronic illnesses may increase the serum level of CDT. False-positive CDT levels may be caused by changes in serum transferrin concentration.

Carbohydrate-deficient transferrin (CDT) has previously been reported to be an excellent marker of male alcoholics. Less is known of its efficiency among women and especially of early-phase alcohol abuse in nonselected populations. The present population-based study examined the diagnostic value of CDT among consecutive women, including 13 teetotallers, 135 social drinkers (mean alcohol consumption 45 +/- 34 g/week), and 57 nonalcoholic heavy drinkers (197 +/- 97 g/week). Sixty-two women with a well-documented history of chronic alcoholism (942 +/- 191 g/week) were also studied, as well as 36 pregnant women used as a reference group. Two weeks of abstinence among 11 alcoholics was followed. The CDT (containing part of isotransferrin with pI = 5.7, 5.8, and 5.9) was separated by anion exchange chromatography and assayed by radioimmunoassay. In the whole material, CDT correlated significantly with alcohol consumption (r = 0.43, p < 0.001) but not with conventional markers (gamma-glutamyltransferase, AST, ALT, and mean corpuscular volume). The CDT values of alcoholics (34 +/- 20 units/liter) were significantly (p < 0.001) higher than those of teetotallers (19 +/- 6 units/liter), social drinkers (20 +/- 6 units/liter), or pregnant women (16 +/- 3 units/liter). Heavy drinkers also had higher values (25 +/- 13 units/liter), but the difference did not reach statistic significance. The specificity of CDT was on the level of conventional markers when the cut-off value was increased from 26 to 29 units/liter. At a specificity of 95%, CDT found 19% of the heavy drinkers and 52% of the alcoholics; the best traditional marker, AST, with a specificity of 97%, found 7% and 56%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

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, middle-aged 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.

Carbohydrate-deficient transferrin (CDT) has been described as a more specific and sensitive marker of recent heavy alcohol consumption as compared with the current tests now available, such as gamma-glutamyltransferase (GGT). Most of the data generated from European populations have not compared the utility of CDT and GGT in the detection of heavy alcohol consumption as a function of gender. We examined the ability of both CDT and GGT to discriminate between 42 men and 18 women with heavy alcohol consumption (> 60 g/day) admitted to an alcohol detoxification center and a group of controls matched for age, race, and gender. CDT was higher, but GGT lower, in control females compared with males. Both CDT and GGT were higher in patients of both genders. At specificities > 90%, the sensitivity of CDT for detecting male alcohol abusers was 79% and for female alcohol abusers 44%. For GGT, the sensitivities were 65% and 44%, respectively. When both tests were used simultaneously, the sensitivity for the detection of alcohol abusers increased to 95% for males and 72% for females. Receiver Operator Characteristic analysis tended to confirm the superiority of CDT over GGT in the detection of heavy alcohol consumption in males, but not in females. A positive relationship was found between serum iron levels and CDT in control females but in no other group. The concordant findings of this American study with those in similar French and Finnish clinical populations, utilizing similar assay techniques, suggest that the measurement of CDT is clinically more useful than GGT in detecting recent heavy alcohol consumption in males.(ABSTRACT TRUNCATED AT 250 WORDS)

We investigated the ability of various blood markers to detect an alcoholic cause of acute pancreatitis. Serum carbohydrate-deficient transferrin (CDT) was significantly correlated with reported 2 month and 7 day ethanol consumptions and was significantly higher in 42 patients with alcoholic acute pancreatitis and in 24 patients with possibly alcoholic acute pancreatitis than in 20 patients with non-alcoholic disease. At a cutoff over 17 U/L, the specificity of CDT was 100% and the sensitivity was 75% to detect an alcoholic cause of acute pancreatitis. The lipase/amylase ratio index, erythrocyte mean corpuscular volume, and gamma glutamyl transferase could not distinguish alcoholic from non-alcoholic acute pancreatitis.

Seven years ago the authors examined 64 consecutive female out-patients with macrocytosis (erythrocyte mean cell volume > or = 100 fl). The cause remained undetermined in 23 (35.9%). Their patient histories were evaluated in 1992, and the new highly specific alcohol marker, serum carbohydrate-deficient transferrin, from the frozen sera taken during the initial study was examined. It was elevated in 6 of the 23 women. Furthermore, four of these six had visited the health centre after 1985 and they all had clinical records indicative of alcohol problems. Because early intervention has proved to be effective, information about the risks of alcohol abuse (intervention) should be given to women with suspect alcohol-induced symptoms or signs.

Carbohydrate deficient transferrin (CDT) has been reported to be one of the best biochemical markers of alcohol abuse. However, a need still exists for a simple and practical method for widespread laboratory use. A semi-automatic (SA) isoelectric focusing (IEF) assay for CDT (SA-IEF-CDT) by a Phast System is introduced here. Different isoforms of transferrin were separated by IEF on polyacrylamide gels (pI 4.0-6.5) and located by immunofixation with an anti-transferrin serum. The precipitation bands were stained with Coomassie Brilliant Blue and quantitated densitometrically. The present method gave a picture of the relative amounts of 10 different transferrin isoforms. The percentage of CDT with pI > or = 5.7 (representing di-, mono- and asialotransferrin) was calculated. For comparisons transferrin bands with pI > or = 5.6 (tri-, di-, mono-, and asialotransferrin), pI > or = 5.8 (mono- and asialotransferrin) and pI > or = 5.9 (asialotransferrin) as well as GGT, ASAT and ALAT were calculated. The method showed good linearity and it identified different isoforms in concentrations of < 10 mg/l of transferrin. The correlation of the present method with a commercially available method employing anion exchange followed by double antibody RIA (AE-RIA-CDT) was good (n = 38, r = 0.924). In 19/20 (95%) of healthy controls, the CDT value was below 4.4% (mean + 2 S.D.) of total transferrin, while higher values were observed in all 20 (100%) alcoholics. In conclusion, the developed semi-automatic method is a practical and reliable alternative for determination of different transferrin isoforms.