Sensitivity Of Carbohydrate-deficient Transferrin Research Articles

Diagnostic sensitivity of carbohydrate deficient transferrin in heavy drinkers.

Background and AimCarbohydrate deficient transferrin (CDT) is the most specific serum biomarker of heavy alcohol consumption, defined as ≥ 350–420 g alcohol/week. Despite introduction of a standardized reference measurement technique, widespread use of CDT remains limited due to low sensitivity. The aim of this study was to determine the factors that affect diagnostic sensitivity in patients with sustained heavy alcohol intake.MethodsPatients with a self-reported history of sustained heavy alcohol consumption were recruited from the hepatology outpatient department or medical wards. Each patient was interviewed with a validated structured questionnaire of alcohol consumption and CDT analysis using the standardized reference measurement technique with high performance liquid chromatography was performed on serum collected at time of interview.Results52 patients were recruited: 19 from the hepatology outpatient department and 33 from general medical wards. Median alcohol intake was 1013 (range 366–5880) g/week over the preceding two week period. 26 patients had a diagnostic CDT based on a threshold value of %CDT > 1.7 indicating heavy alcohol consumption, yielding a sensitivity of 50%. Overweight/obesity (defined as body mass index (BMI) ≥ 25 kg/m2 in Caucasians and ≥ 23.0 kg/m2 in Asians), female gender and presence of cirrhosis were independently associated with non-diagnostic %CDT (≤ 1.7).ConclusionsCDT has limited sensitivity as a biomarker of heavy alcohol consumption. Caution should be applied when ordering and interpreting %CDT results, particularly in women, patients with cirrhosis and those with an elevated BMI.

Should we use carbohydrate deficient transferrin as a marker for alcohol abusers?

Carbohydrate deficient transferrin (CDT) is one of the conventional markers for chronic alcohol consumption, is used by researchers and clinicians. A number of enzymes are affected by ethanol intake. The induction or inhibition of sialyl transferase and plasma sialidase may be involved in the CDT level elevation. An alteration of protein transport during post-translational modification could be a primary mechanism in the impairment of protein metabolism associated with chronic alcohol abuse. Transferrin being a steroid responsive protein, sex-based hormonal variations might contribute to the lower sensitivity of CDT. Varying hormonal statuses such as pregnancy, use of contraceptives, menopause/ menstrual cycle can alter iron homeostasis in women. CDT levels are markedly affected by iron homeostasis. Several CDT assay methods appeared promising, but it is not readily apparent which technique is the most accurate. Moreover, false-positive results of CDT have been reported in non-alcohol related hepatic failure and in rare conditions. Therefore clinical interpretation of CDT needs careful assessment in patients with alcohol-related or non-alcohol-related health disorders.

Biological Markers of Alcohol Consumption in Nondrinkers, Drinkers, and Alcohol‐Dependent Brazilian Patients

The purpose of this study was to compare the sensitivity and specificity of some new and traditional biological markers and indicators of health among Brazilian nondrinkers, drinkers, and alcohol-dependent patients. We evaluated 130 nondrinkers, 167 drinkers, and 183 alcohol-dependent drinkers from Brazil who participated in the WHO/ISBRA Study on State and Trait Markers of Alcohol Use and Dependence. A standardized WHO/ISBRA Interview Schedule provided background information on the subjects' characteristics including reported health problems and alcohol consumption. Blood samples were analyzed for aspartate aminotransferase (AST), carbohydrate deficient transferrin (CDT), gamma-glutamyltransferase (GGT), blood alcohol levels (BAL), and platelet adenylate cyclase activity (basal levels [AC] and levels after stimulation with Gpp(NH)p, cesium fluoride, and forskolin). The alcohol-dependent drinkers presented higher levels of AST, GGT, AC, CDT, and BAL than the nondrinkers and drinkers, whose levels were similar. Sex differences in the sensitivity of CDT and AC were found. The alcohol-dependent women presented a lower prevalence of abnormal values of CDT and Gpp(NH)p-stimulated AC than the alcohol-dependent men, despite the fact that they presented similar alcohol consumption levels. The alcohol-dependent drinkers presented a higher prevalence of clinical disorders than the nondrinkers and drinkers. The drinkers and alcohol-dependent patients presented significantly higher rates of gastritis than the nondrinkers. Sex differences in the sensitivity of CDT and AC suggest that these markers are not as sensitive at detecting excessive alcohol use in women as they are in men. If data from this Brazilian sample are compared with those reported for international samples, relevant differences are detected, which suggests that genetic and cultural differences should be considered in the selection of biological markers of heavy alcohol consumption.

Diagnostic usefulness of carbohydrate-deficient transferrin for detecting alcohol-related problems in hospitalized patients.

We evaluated the diagnostic usefulness of carbohydrate-deficient transferrin (CDT) for detecting alcohol-related problems (ARP) in hospitalized patients, assessed potential differences according to gender and age, and compared this value to the other screening measures conventionally used, namely the CAGE questionnaire and standard biological markers MCV (mean corpuscular volume) and GGT (gamma-glutamyltransferase). CDT sensitivity for detecting ARP was 70%, specificity 75% and area under the receiver operating characteristic curve 0.76%. Its sensitivity was shown to be lower both in the female group (65 vs 71%) as well as in the younger-age group whereas its specificity was lower in the liver-damaged group (55%). CDT diagnostic value did not exceed that of CAGE (sensitivity 78% and specificity 99%), MCV (sensitivity and specificity 74%) or GGT (sensitivity 82% and specificity 53%) but was better than those of other biochemical measures. We conclude that CDT is an effective biological marker for the detection of ARP among hospitalized patients, but that its diagnostic usefulness does not exceed that of some other alternative measures commonly used.

Validity of carbohydrate deficient transferrin and other markers as diagnostic aids in the detection of alcohol related seizures

OBJECTIVEThe 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...

Is carbohydrate deficient transferrin a useful marker of harmful alcohol intake among surgical patients?

To find out whether the biological marker, carbohydrate deficient transferrin (CDT), was helpful in the detection of alcoholic patients in a surgical unit. Prospective open study. Teaching hospital, Denmark. 286 men and 248 women admitted to the department of surgical gastroenterology between March and July 1996. Specific interview about drinking and correlation with CDT concentration. 31 men (13%) and 10 women (3%) were alcoholic and at special risk of operation. The correlation between intake and CDT:transferrin ratio was 0.63 for men and 0.53 for women. The correlation between consumption and CDT was better, being 0.77 and 0.58, respectively. Younger women had the lowest correlation (0.33). Sensitivity of CDT for men and women was 100% and 80%, respectively; the specificity was 97% and 96%; the positive predictive value 82% and 44%; and the negative predictive value 97% and 99%. CDT is a valid marker of harmful alcohol intake among surgical patients, except among younger women.

Carbohydrate-deficient transferrin: marker of actual alcohol consumption or chronic alcohol misuse?

Carbohydrate-deficient transferrin (CDT) is a useful indicator of excessive alcohol consumption with higher sensitivity and specificity than other markers that are used. In the present study, CDT was analysed in 161 patients hospitalized in a surgical ward to evaluate whether history of drinking and chronic alcohol misuse are important determinants of CDT elevations. Fifty-one of the patients were diagnosed as alcohol-dependent and they all reported a long history of alcohol abuse. Several of these, as well as many of the non-dependent patients, reported a high, recent alcohol consumption (> or = 60 g/day for the previous 2 weeks). CDT performed better in detecting patients with alcohol dependency than in detecting patients with high alcohol consumption irrespective of dependency, showing higher sensitivity (47 vs 37%), likelihood ratio (4.7 vs 3.4), and a statistically significant difference in the receiver-operating characteristic curve areas (P = 0.04 in a two-tailed comparison test). In two subgroups, one with alcohol-dependent and one with non-dependent patients, consuming similar amounts of alcohol (range: 60-170 g/day), the sensitivity of CDT was 52 and 5%, respectively. We conclude that CDT is a better marker for patients with chronic alcohol misuse than as a marker for high actual alcohol consumption alone.

Female alcoholic outpatients and female college students: a correlational study of self-reported alcohol consumption and carbohydrate-deficient transferrin levels.

We sought to test the efficacy of two biochemical markers of alcohol consumption, gamma glutamyl transpeptidase and carbohydrate deficient transferrin, as indicators of heavy alcohol consumption in a female population. Using a sample of female outpatient alcoholics (n = 36) and a comparison group of female college students (n = 50), alcohol intake was monitored by self-report at approximately 90-day intervals over a period of 12 months. Gamma glutamyl transpeptidase (GGTP) and carbohydrate-deficient transferrin (CDT) values were determined for each sampling period. The criterion for heavy alcohol consumption was set at 140 g/alcohol/week for a 90-day period. Receiver operating characteristic (ROC) curves were plotted, area under the curve (Az) computed, and sensitivity and specificity calculated for both CDT and GGTP. ROC curves provide a graphical illustration of the association between the specificity and sensitivity of any diagnostic test over all possible cutpoint values. A significant, positive correlation between the amount of alcohol consumed and GGTP activity was recorded for the outpatient alcoholic group. Among the college students, there was a significant, positive correlation between CDT levels and alcohol consumed for the second reporting period. The sensitivity of the individual biochemical markers was low but, when used in combination, sensitivity was 66% and specificity, 80%. When a more stringent criterion for heavy alcohol consumption was applied (420 g/alcohol/week), the sensitivity of CDT actually decreased. CDT, used alone, is a poor indicator of heavy alcohol consumption in female subjects. When GGTP measures are used in conjunction with CDT, detection of heavy alcohol consumption may be enhanced to useful levels.

Der neue ,,Alkoholmarker" carbohydratdefizientes Transferrin (CDT)

Many alcoholics deny any abuse, and hence it is often difficult to diagnose alcohol abuse. Laboratory parameters, such as gamma-glutamyltransferase (gamma-GT) and the mean corpuscular volume of erythrocytes (MCV), are often used to diagnose recent high alcohol intake. However, these parameters indicate elevated alcohol consumption only indirectly, e.g. if the elevation is due to an organ lesion caused by alcohol. In recent literature, CDT (carbohydrate-deficient transferrin) has been suggested as a most promising laboratory parameter indicating noxious alcohol consumption. The clinical value of CDT is compared to other "alcohol markers". CDT has the highest sensitivity and specificity in selected samples taken from alcoholics. However, the sensitivity of CDT is rather low in population surveys. Thus, CDT cannot be recommended for the screening of alcoholics. Furthermore, in view of the high cost of measurement, a close indication for application is urgent. Some examples of an indication in neurological and psychiatric diagnostics are critically discussed.

Carbohydrate-deficient transferrin and alcohol dependency: variation in response to alcohol intake among different groups of patients.

Carbohydrate-deficient transferrin (CDT) and gamma-glutamyltransferase (GT) were evaluated as markers of alcohol dependency in two different groups of patients. Sensitivity of CDT was nearly 75% for patients hospitalized for detoxification, but lower than 50% for alcohol-dependent patients admitted to acute surgery. CDT correlated with self-reported alcohol consumption in both groups, and sensitivity increased with higher alcohol intake. Sensitivity of CDT for females in both groups was considerably lower than for males, although their alcohol consumption was not significantly different. Serum activity of GT showed almost identical performance as CDT when evaluated by receiver-operating characteristics curve analysis (ROC-analysis), but sensitivity and specificity of the two markers varied differently with both alcohol consumption and age. Among the surgical patients, the highest sensitivity of CDT was found for the middle-aged patients (36 to 50 years), whereas the highest sensitivity of GT was found for the eldest. A tendency for similar age-related differences were also observed among the patients warded for detoxification, but these differences were not statistically significant. A particular difference between the two groups was noted among the youngest patients (21 to 35 years), with a very low sensitivity of CDT (< 20%) for the surgical patients and a high sensitivity (77%) for the detoxification group. This difference was not only caused by differences in the present alcohol consumption, but would also be related to differences in drinking pattern or duration. Two commercial kits analyzing CDT were compared and ROC-analysis indicated identical performance of the two. However, a kit determining CDT as percentage of total transferrin showed a somewhat higher sensitivity among patients with low serum transferrin. We conclude that CDT and GT show variant responses to alcohol consumption in different groups of patients. The level of the two markers are related to sex, age, and alcohol consumption. Furthermore, the performance of both markers depend on the patients' history of alcohol abuse. CDT and GT are statistically independent markers and may therefore supplement each other.

High-performance liquid chromatography improves diagnostic efficiency of carbohydrate-deficient transferrin.

Carbohydrate-deficient transferrin (CDT) is considered a useful biochemical marker of regular high alcohol intake. CDT was measured in the sera of 51 alcohol abusers, 20 patients with non-alcoholic liver disease and 30 healthy controls with an alcohol intake of < 30 g/day. The mean CDT levels of these three groups respectively were determined with high-performance liquid chromatography (HPLC; 4.6 +/- 5.2%; 0.7 +/- 0.2%; 0.7 +/- 0.2%) and with a radioimmunoassay after microcolumn anion-exchange chromatography (MAEC/RIA; 34.2 +/- 26.9 U/l; 16.9 +/- 3.8 U/l; 18.0 +/- 5.7 U/l). CDT levels in patients with severe alcohol abuse (161.6 +/- 96.4 g/day) were significantly higher than in the two other groups under investigation (P < 0.0001). In heavily drinking subjects, the mean daily alcohol intake correlated with aspartate aminotransferase levels (ASAT) but not with the CDT levels determined either with HPLC or MAEC/RIA. With both methods, the CDT levels were slightly higher in patients with an ASAT concentration > 30 U/l, which may indicate an advanced liver damage (P < 0.05). Analysis of receiver-operating characteristic (ROC) plots demonstrated that the diagnostic accuracy of the HPLC method, which determines the relative amount of CDT, was significantly higher than the established MAEC/RIA method, which measures the absolute amount of CDT (area under the ROC curve: 0.95 +/- 0.02 vs 0.73 +/- 0.05; P < 0.0001). At a specificity of > 95%, the sensitivity of CDT determined with HPLC and MAEC/RIA was 80 and 47%, respectively. In addition, HPLC may be a useful and reliable method for the determination of this important biochemical marker, since the HPLC chromatogram is a visible document of the successful isotransferrin separation and measurement.

REPLY: SUPERIOR DIAGNOSTIC ACCURACY OF CARBOHYDRATE-DEFICIENT TRANSFERRIN OVER GAMMA-GLUTAMYLTRANSFERASE

In his letter, Dr Rosalki (1996) criticizes our claim (Stauber et al, 1995) of superior sensitivity of carbohydrate-deficient transferrin (CDT) over that of gamma-glutamyltransferase (gamma-GT). It was not our intention to claim that sensitivity of CDT alone is superior to that of gamma-GT, but that sensitivity and specificity of CDT together, and thus its overall diagnostic accuracy, are superior. For comparison of CDT with gamma-GT, we analysed only data obtained from outpatients who had various kinds of chronic liver disease, but were not preselected because of an elevated gamma-GT. As can be seen in Table 2 of our article (Stauber et al., 1995), the sensitivities of CDT (85%) and gamma-GT (83%) were comparable, while the specificity of CDT (83%) was superior to that of gamma-GT (16%). These findings are consistent with a previous study by Bell et al. (1993), who reported sensitivities of 61% for CDT and 85% for gamma-GT and specificities of 92% for CDT and 18% for gamma-GT. Based on these data, it may be clearly concluded that overall diagnostic accuracy of CDT is superior to that of gamma-GT in patients with liver disease.

Carbohydrate-deficient transferrin in alcohol and nonalcohol abusers with liver disease.

Carbohydrate-deficient transferrin (CDT) has been demonstrated to be a marker of prolonged heavy alcohol consumption. We compared this marker with gamma-glutamyltranspeptidase (GGT) and mean corpuscular volume (MCV) in alcohol and nonalcohol abusers with liver disease. Our results confirm that the sensitivity of CDT in alcoholics is high, although lower than that of GGT and MCV; however, the specificity of CDT was higher than that of the other two markers. This finding supports the notion that CDT is only partially influenced by the presence of liver damage, whereas increases of GGT and MCV are greatly affected by several factors, including liver damage and drugs. Moreover, we observed that the sensitivity and the specificity of CDT were greater than those of GGT and MCV in younger drinkers.

Carbohydrate‐Deficient Transferrin as a Marker of Alcohol Abuse: Relationship to Alcohol Consumption, Severity of Liver Disease, and Fibrogenesis

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)

Detection of Relapses in Alcohol‐Dependent Patients Using Carbohydrate‐Deficient Transferrin: Improvement with Individualized Reference Levels during Long‐Term Monitoring

The present study examined whether the sensitivity of carbohydrate-deficient transferrin (CDT) in serum, a biochemical marker of recent excessive alcohol consumption, could be improved during long-term monitoring by introducing individualized cut-offs between normal and elevated CDT levels. Alcohol-dependent male outpatients (n = 22), trying to abstain from alcohol for 6 months, were monitored by comparing weekly measurements of CDT with self-reports of alcohol consumption three times/week and daily urinary levels of 5-hydroxytryptophol (5-HTOL), a new marker of recent alcohol intake. The method used to calculate cut-offs was based on the intraindividual variation in CDT not dependent on excessive alcohol consumption or analytical variations. An increase in CDT exceeding the minimum level for each patient by 3 and 4 times the mean coefficient of variation for healthy social drinkers (i.e., by 30% and 40%) was compared as an indication of alcohol consumption, even if the value did not exceed the conventional cut-off. By using individualized CDT cut-off points, 68 and 41 episodes of drinking were detected in the patients with the cut-offs of > 30% and > 40%, respectively, as compared with 25 with the conventional limit. Most episodes could be verified clinically and/or by elevated urinary 5-HTOL levels during the 2-week period preceding each serum sampling. The results suggest that the possibility to detect relapses by CDT can be improved during long-term monitoring of alcohol-dependent outpatients by introducing individualized cut-off points between normal and elevated CDT levels.

CARBOHYDRATE DEFICIENT TRANSFERRIN LEVELS IN HAZARDOUS ALCOHOL CONSUMPTION

Little information is available on the value of carbohydrate deficient transferrin (CDT) in detecting persons with hazardous alcohol consumption. In the present study isoelectric focusing (IEF) and immunofixation were used to examine the sensitivity of CDT in hazardous drinkers compared with control subjects and alcohol dependent persons. Elevated CDT levels (> 100 mg/l) were found in 62% of hazardous drinkers and 67% of alcohol dependent persons compared with only 5% of controls. CDT was more sensitive than serum gamma glutamyltransferase (GGT) activity in detecting hazardous alcohol consumption (sensitivity of GGT 19%; P < 0.001), but was of comparable sensitivity to GGT for alcohol dependence. Neither the transferrin index nor transferrin ratio offered any advantage over CDT in detecting hazardous consumption. We conclude that serum CDT, as measured by IEF and immunofixation, is a sensitive and specific test for hazardous drinking.

Carbohydrate-deficient transferrin and other markers of high alcohol consumption: a study of 502 patients admitted consecutively to a medical department.

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 and gamma-glutamyltransferase as markers of heavy alcohol consumption: gender differences.

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)

Carbohydrate-deficient transferrin during 3 weeks' heavy alcohol consumption.

To study the effect of controlled heavy drinking of 60 g ethanol/day for 3 weeks on carbohydrate-deficient transferrin (CDT), a commercial double antibody kit (CDTect) was used. By the end of the third drinking week, a statistically significant increase in the mean CDT level was observed. When compared to AST and gamma-glutamyltransferase, CDT was a more informative marker. However, only in 2 of the 10 volunteers did CDT exceed the upper normal level (20 units/liter) recommended by the manufacturer. This indicates that the sensitivity of CDT to detect heavy drinking is lower than that previously reported. The higher accuracy has in general been obtained in studies comparing healthy controls with a low alcohol consumption to alcoholics with an alcohol consumption higher than that used in the present experiment. Our results suggest that it remains to be established whether CDT, although better than AST and gamma-glutamyltransferase, will provide a clinically useful tool in identifying heavy drinkers in populations covering a wide range of alcohol consumption.