Marker Of Alcohol Consumption Research Articles

Association of carbohydrate-deficient transferrin (CDT) and gamma-glutamyl-transferase (GGT) with serum lipid profile in the Finnish population

Background: Moderate consumption of alcohol may reduce mortality from vascular diseases. The beneficial effects of alcohol may partly be mediated by its effects on lipoprotein metabolism. We studied the connection between alcohol consumption and the serum lipid profile from a well-documented national health program study. Methods and results: Carbohydrate-deficient transferrin (CDT) and gamma-glutamyl-transferase (GGT) were used as biochemical markers for alcohol consumption. The laboratory analyses were carried out on 5675 subjects (3097 males and 2578 females). The subjects were divided into quartiles on the basis of CDT or GGT value. The highest CDT quartile and the lowest GGT quartile seemed to be associated with a favorable lipid profile and the lowest CDT quartile and the highest GGT quartile were associated with an unfavorable lipid profile. Serum high density lipoprotein (HDL) cholesterol values were significantly higher and triglycerides lower with increasing serum CDT concentrations for both men and women. Increasing serum GGT was associated with higher serum total cholesterol and higher triglycerides in both men and women and lower HDL cholesterol in men. Conclusions: CDT and GGT seem to detect different populations of subjects in regard to lipid metabolism. These observations may lead to a better understanding of the effects of alcohol consumption on lipids as well as mechanisms behind favorable and detrimental effects of alcohol on vascular diseases. Condensed abstract: Carbohydrate-deficient transferrin (CDT) and gamma-glutamyl-transferase (GGT) were used as biochemical markers for alcohol consumption. A total of 3097 males and 2578 females were divided into quartiles on the basis of their CDT or GGT values. The highest CDT quartiles had higher HDL and lower triglycerides, whereas the highest GGT quartiles appeared to be associated with higher total cholesterol and triglycerides in both genders and lower HDL in men. CDT and GGT seem to detect different populations of subjects in regard to lipid metabolism. These observations may have important clinical and public health implications.

Vitamin B12 and hepatic enzyme serum levels correlate in male alcohol-dependent patients.

- Vitamin B12 serum levels and markers for alcohol consumption were determined in 80 male alcohol-dependent patients. Spearman correlation coefficients (r(S)) were calculated. Significant positive correlations between vitamin B12 and hepatic enzyme values were found (gamma-glutamyltransferase: r(S) = 0.58; alanine aminotransferase: r(S) = 0.43; aspartate aminotransferase: r(S) = 0.47; glutamate dehydrogenase: r(S) = 0.43; all P: < 0.001). Therefore, for a proper interpretation of vitamin B12 levels, it may be clinically relevant to take markers of hepatocellular damage into account.

Dose response of laboratory markers to alcohol consumption in a general population.

The dose response to alcohol use of carbohydrate-deficient transferrin (CDT), gamma-glutamyltransferase (GGT), and their combination (gamma-CDT) was studied in an age- and gender-stratified, random sample from Finland in 1997. A linear association with a threshold between alcohol consumption and the three markers was observed. Body mass index was negatively associated with CDT and positively with GGT Age was positively associated with GGT and gamma-CDT In conclusion, CDT appears to be an early phase marker of alcohol consumption. The combined marker, gamma-CDT, was less associated with factors such as body mass index but more strongly correlated with alcohol consumption than were the two markers separately.

Ethyl glucuronide in human hair.

Ethyl glucuronide (EtG) is considered to be a promising candidate marker of alcohol consumption, but exhibits a short window of detection in blood or urine. Keratinized tissues are known to retain foreign substances and to provide a greater retrospective window of detection than body fluids. Therefore, post-mortem hair, skin swabs, and stratum corneum samples were collected from four subjects with a reported history of alcohol misuse and from seven subjects with a report of regular, socially accepted drinking behaviour, and were investigated for EtG. Additionally, certain specimens were collected from three children, who had not yet consumed any alcoholic beverages. EtG was detectable in most of the hair and stratum corneum samples as well as in perspiration stains from alcohol-consuming subjects. The results indicated that EtG might be formed locally in very small and highly variable amounts. The most important finding was that EtG cannot be expected to be generally detectable in keratinized tissues or perspiration stains from alcohol-drinking subjects, whereas a positive result is always associated with recent alcohol consumption.

Ethyl glucuronide: a marker of recent alcohol consumption with clinical and forensic implications

A marker with a specific time spectrum of detection and both high sensitivity and specificity is required to diminish the clinically as well as forensically important gap on the time axis between short- and long-term markers of alcohol consumption like ethanol and CDT, GGT or MCV, respectively. Ethyl glucuronide (EtG) is a non-volatile, water-soluble, stable upon storage, direct metabolite of ethanol with a molecular weight of 222 g/mol that can be detected in body fluids for an extended time period after the complete elimination of alcohol from the body. We investigated 107 urine and 78 serum samples of a total of 107 inpatients in 4 groups: (1) 33 inpatients in acute alcohol withdrawal and long term treatment; (2/3) 29 and 15 addicted forensic psychiatric inpatients (§64 StGB, penal code); (4) 30 recently detoxified inpatients of a station for long term treatment by LC/MS-MS with the internal standard d5-EtG and additionally in the fourth group of patients also by gas chromatography/mass spectrometry (GC/MS). In 2 out of 33 inpatients of the first group, EtG could be determined 3 days after hospitalization; in an other subject, a relapse could be detected. In 2 out of 29 and in 1 out of 15 forensic inpatients of group 2 and 3, respectively—where neither clinical impression nor routine laboratory findings gave an indication for relapse—concentrations of EtG ranged between 0.1 and 18 mg/l in urine. For the serum samples of the 30 inpatients of group 4, we could demonstrate a total agreement for the results of the GC/MS and the LC/MS-MS method as to whether a sample was found to be positive or negative for EtG. We suggest that these results strengthen our earlier findings that ethyl glucuronide is a marker of alcohol consumption in general that can be detected for an extended time period after the complete elimination of alcohol from the body and a marker for relapse control with a specific time frame of detection intermediate between short- and long-term markers.

Relative Versus Absolute Carbohydrate‐Deficient Transferrin as a Marker of Alcohol Consumption in Patients With Acute Alcoholic Hepatitis

Carbohydrate-deficient transferrin has been described as a sensitive and specific marker for alcohol consumption. This study investigated the usefulness of carbohydrate-deficient transferrin as a marker of alcohol consumption in acute alcoholic hepatitis. Absolute concentrations (U/I) and relative values (%) of carbohydrate-deficient transferrin determined in serum with commercial assays, as well as conventional markers for alcohol consumption, were compared with the alcohol consumption (as estimated by a questionnaire) in patients with acute alcoholic hepatitis (n = 19), alcoholic liver cirrhosis (n = 37), and nonalcoholic liver diseases (n = 16). The concentration of carbohydrate-deficient transferrin was increased (p < 0.001) in nonabstaining patients (median intake 80 g alcohol/day) with alcoholic liver cirrhosis (45.7 +/- 30 U/l), but not in patients with acute alcoholic hepatitis (20.0 +/- 7.8 U/l) despite higher alcohol consumption (median 130 g/d), nor in abstainers with alcoholic liver cirrhosis (19.4 +/- 6.0 U/l) or nonalcoholic liver disease (18.5 +/- 6.7 U/l). However, the relative values of carbohydrate-deficient transferrin were increased both in acute alcoholic hepatitis (7.9 +/- 2.1%) and nonabstainers with alcoholic liver cirrhosis (7.4 +/- 2.8%), but not in abstainers with alcoholic liver cirrhosis (4.6 +/- 3.5%) or nonalcoholic liver disease (3.8 +/- 0.9%) (p < 0.001). In acute alcoholic hepatitis, the sensitivity and specificity were only 32% and 87% for absolute concentrations, respectively, but 79% and 97% for relative values of carbohydrate-deficient transferrin. The concentrations of carbohydrate-deficient and total transferrin in serum were strongly correlated (r = 0.60; p = 0.008). The relative value (% of total), but not the absolute concentration, of carbohydrate-deficient transferrin in serum is a useful marker of alcohol consumption in acute alcoholic hepatitis.

Relative Versus Absolute Carbohydrate-Deficient Transferrin as a Marker of Alcohol Consumption in Patients With Acute Alcoholic Hepatitis

Relative Versus Absolute Carbohydrate-Deficient Transferrin as a Marker of Alcohol Consumption in Patients With Acute Alcoholic Hepatitis

Limitations of CDT and GGT in detecting relapses in patients attending an alcohol problems clinic.

Biochemical markers of alcohol consumption are useful for the detection and monitoring of problem drinking. Blood samples from 37 patients attending an alcohol treatment clinic were analysed for GGT and %CDT, and results were compared with self-reported periods of abstinence and alcohol consumption. Poor correlation was obtained between GGT and %CDT, and between these assays and self-reported alcohol use. The apparent sensitivity and specificity of GGT (57%, 63%) and %CDT (43%, 88%), were considerably lower than those reported by other workers.

Serum ubiquitin levels in patients with alcoholic liver disease.

Serum concentrations of free ubiquitin and multiubiquitin chain as determined by immunoassays were compared between 10 healthy subjects, and 11 patients with alcoholic hepatic fibrosis, 10 with alcoholic cirrhosis, and 6 with viral liver cirrhosis. All measurements of multiubiquitin chains were expressed in terms of a standard multiubiquitin chain reference preparation 1. Serum concentrations (mean +/- SD) of free ubiquitin and multiubiquitin chains were significantly higher in patients with alcoholic cirrhosis (63.5 +/- 33.7 ng/ml and 7.5 +/- 4.6 ng/ml) than in the normal subjects (29.6 +/- 6.6 ng/ml, p < 0.05 and 4.1 +/- 1.7 ng/ml, p < 0.05), and those with alcoholic hepatic fibrosis (34.8 +/- 16.3 ng/ml, p < 0.05 and 3.0 +/- 0.7 ng/ml, p < 0.05) and viral liver cirrhosis (28.8 +/- 7.5 ng/ml, p < 0.05 and 4.2 +/- 1.3 ng/ml, p < 0.05). Serum levels of both forms of ubiquitin in six patients with alcoholic cirrhosis showed a tendency to decline after 3 months of abstinence. In a total of 14 patients with alcoholic liver damage, 11 with brain atrophy had significantly higher serum levels of both ubiquitin forms than did three patients without brain atrophy (p < 0.05). No correlation was seen between serum concentrations of either form of ubiquitin and liver function test results in the patients with alcoholic liver damage. However, serum levels of both forms of ubiquitin levels correlated significantly with cumulative alcohol intake (p < 0.05). A significant correlation (p < 0.05) also was observed between serum levels of multiubiquitin chains and mean corpuscular volume, a marker of alcohol consumption. These results suggest that the serum concentrations of ubiquitin, especially multiubiquitin chain is a good marker for the diagnosis of alcoholic cirrhosis.

Ethyl glucuronide--a marker of alcohol consumption and a relapse marker with clinical and forensic implications.

Ethyl glucuronide (EtG) is a non-volatile, water-soluble, direct metabolite of ethanol that can be detected in body fluids and hair. We investigated urine and serum samples from three patient groups: (1) 33 in-patients in acute alcohol withdrawal; (2) 30 detoxified in-patients (treated for at least 4 weeks) from a 'motivation station'; and (3) 43 neuro-rehabilitation patients (non-alcoholics; most of them suffering from stroke, traumatic brain injury, Parkinson's disease etc.) using gas chromatography/mass spectrometry (GC/MS) with deuterium-labelled EtG as the internal standard and additionally in the second group of patients using liquid chromatography (LC/MS-MS). We found no correlation between the concentration of EtG in urine at hospitalization and the blood-ethanol concentration (r = 0.17), the time frame of detection (r = 0.5) or the total amount of clomethiazole required for the treatment of withdrawal symptoms (r = 0.28). In four out of 30 in-patients from the 'motivation station'--where neither clinical impression nor routine laboratory findings gave indications of relapse--concentrations of EtG in urine ranged between 4.2 and 196.6 mg/l. EtG concentrations in urine of between 2.89 and 23.49 mg/l were found in seven out of 43 neuro-rehabilitation patients using GC/MS. The GC/MS and the LC/MS-MS results showed a correlation of 0.98 with Pearson's correlation test and 1.0 with Spearman's correlation test. We suggest that EtG is a marker of alcohol consumption that can be detected for an extended time period after the complete elimination of alcohol from the body. When used as a relapse marker with a specific time frame of detection intermediate between short- and long-term markers, EtG fills a clinically as well as forensically important gap. Its specificity and sensitivity exceed those of all other known ethanol markers.

Carbohydrate-deficient transferrin and gamma-glutamyltransferase are inversely associated with lipid markers of cardiovascular risk.

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.

The Effect of Drinking Intensity and Frequency on Serum Carbohydrate‐Deficient Transferrin and γ‐ Glutamyl Transferase Levels in Outpatient Alcoholics

Whereas heavy alcohol consumption is known to elevate serum carbohydrate-deficient transferrin (CDT) and gamma-glutamyl transferase (GGT) levels, the contribution of drinking pattern to these effects is not completely understood. We present data on 423 men and 146 women evaluated 1 year after treatment in a large-scale alcoholism treatment study (Project MATCH). Relationships between drinking frequency (number of days drinking), intensity (drinks per drinking day), and blood levels of CDT and GGT were analyzed by using response surface regression models and thin-plate spline-smoothing techniques. Both models indicated differences between CDT- and GGT-drinking pattern relationships in men and, also, a difference between men and women in CDT drinking-pattern relationships. For men, CDT levels appeared to respond primarily to frequency of drinking, whereas GGT was influenced primarily by drinking intensity. For women, both CDT and GGT were influenced more by drinks per drinking day (intensity) than by number of days drinking (frequency). The data confirm both the independent nature of these biological markers of alcohol consumption and gender differences in alcohol-induced CDT response reported previously.

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.

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

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

Serum carbohydrate-deficient transferrin in patients with nonalcoholic liver disease and with hepatocellular carcinoma

Serum carbohydrate-deficient transferrin (CDT) is used as a reliable and specific marker of alcohol consumption. However, recent studies have shown false-positive CDT test results in nonalcoholic liver disease. We examined the clinical significance of serum CDT in nanalcoholic liver disease, especially hepatocellular carcinoma. Serum CDT was measured in 23 teetotallers, 56 patients with alcoholic liver disease, 84 patients with viral liver disease and 67 patients with hepatocellular carcinoma, with an Axis %CDT radioimmunoassay kit, and the results were expressed as percentages of the total transferrin (%CDT). The mean serum %CDT value was increased 1.8-fold in alcoholic liver fibrosis and 3.8-fold in alcoholic liver cirrhosis compared with the teetotallers. The serum %CDT values in viral chronic hepatitis were similar to those of the teetotallers, and were increased 2.0-fold in viral liver cirrhosis. False-positive results were found in 10 (37%) of the 27 patients with viral liver cirrhosis. The mean serum %CDT value was increased 2.5-fold in hepatocellular carcinoma, and false-positive results were found in 31 (46%) of the 67 patients. The serum %CDT value was related to the severity of Child grade, the size of tumor and the grade of histological differentiation. These results suggest that the ability of serum CDT test to detect chronic alcoholism may be reduced in patients with nonalcoholic liver cirrhosis and those with hepatocellular carcinoma.

Treatment of alcohol dependence: experiences of using biological markers in monitoring and prevention of relapse.

The treatment modalities of alcohol consumption are briefly reviewed with special emphasis on brief motivational intervention. The usefulness of laboratory markers of alcohol consumption in identifying relapses and as adjuncts to therapy programmes is highlighted. The recently developed marker, carbohydrate-deficient transferrin, has proven to be a promising test in its use to monitor relapse in patients using each patient's cut-off value offers advantages over group cut-offs.

Carbohydrate‐Deficient Transferrin as an Indicator of Drinking Status During a Treatment Outcome Study

Biological markers of alcohol consumption have been used in both clinical and research settings to aid in the identification of relapse drinking. Although carbohydrate-deficient transferrin (CDT) has been shown to be a sensitive and specific marker for the identification of heavy drinkers, little data are available as to its utility as a marker for relapse drinking during treatment, particularly in comparison with the more widely used serum gamma-glutamyltransferase (GGT). CDT and GGT were measured in 35 male alcoholics before entering, and every 4 weeks during, a 12-week outpatient treatment trial combining pharmacotherapy and cognitive behavioral therapy. CDT and GGT were again measured 14 weeks after completion of treatment. During the 12-week treatment period, CDT showed a significant difference in those individuals who abstained from drinking (30% decrease), compared with those who relapsed (10% increase). GGT decreased on average in all individuals, and the change from treatment entry did not differ significantly across the drinking outcome groups. The change in CDT, but not GGT, from study entry to termination, significantly correlated with total alcohol consumption during the trial. At the 14-week posttreatment, follow-up evaluation CDT showed about a 60% elevation and GGT showed a 30% elevation, on average, from study entry values in those individuals who had relapse drinking by self and/or collateral report. The change in both markers differed between those individuals who remained abstinent or relapsed during the poststudy period. In general, the change in CDT from pretreatment levels seemed more sensitive to drinking status during treatment and follow-up than GGT. This indicates that CDT may be more sensitive marker for evaluating drinking status during both clinical and research treatment trials.

Relative kindling effect of readmissions in alcoholics.

To determine if there is an increase in the risk of seizure activity when patients experience recurrent alcohol detoxification, the histories of 360 alcoholics who had at least two admissions for alcohol detoxification, between November 1987 and August 1992, were reviewed retrospectively. All subjects were treated with tapering doses of chlordiazepoxide as required, to control symptoms/signs of alcohol withdrawal. Subjects with a seizure history were prophylactically treated with tapering doses of chlordiazepoxide. No seizures were observed during detoxification in any of these subjects. In this group of readmitted subjects, there was no correlation between self-reported duration of alcohol consumption or average daily intake of alcohol. A significant correlation was observed between seizure history and number of detoxification admissions and neurological admissions, but not for other medical/surgical admissions, nor for admissions for rehabilitation. At the time of initial admission, laboratory parameters did not distinguish those subjects with seizures from those without. At the time of readmission, mean corpuscular volume and gamma-glutamyl transpeptidase, both markers of alcohol consumption, were higher in the group with seizures.

Carbohydrate-deficient transferrin as a screening marker for drinking in a general hospital population.

We investigated the usefulness of the laboratory marker of alcohol consumption carbohydrate-deficient transferrin (CDT) in 101 consecutively admitted patients in a surgical and internal medical ward of a hospital in a rural wine-growing area. Four major aspects were considered: the influence of liver disease, the method of expression of CDT values (relative % vs absolute units/1), level and pattern of alcohol consumption and comparison with y-glutamyl transferase (GGT). The results show that %CDT is a more valuable discriminating marker of high alcohol consumption than absolute CDT values and its usefulness in this respect is independent of changes in serum total transferrin levels, as in liver disease. Sensitivity and specificity of % CDT were 70 and 98% respectively, compared with 65 and 83% respectively for GGT.

Les ivresses dans le trafic à Genève: Abus occasionnels ou alcoolisme

The main aim of the study is to measure the importance of alcoholism amongst alcohol intoxication (up to the Swiss legal BAC: 0.8 gr/kg) in traffic. The method used describes the characteristics of all cases of inebriety (amongst pedestrians and drivers) recorded by the police during one year and relates this with complementary data such as the determination of a biological marker of alcohol consumption (Gamma Glutamyl Transferase), or DWI recidivism. Results of general interest are: 22% of recorded cases of alcohol intoxication are recidivists; about one third of the cases of alcohol intoxication registered are due to alcoholism rather than to social drinking. A preventive policy in road traffic safety must integrate the problems, caused by alcoholism, on Public Health.