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

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

Evaluation of the diagnostic utility of carbohydrate-deficient transferrin in chronic alcoholism: Results from Southwest China

Although recent gathered evidence indicates that obtaining the diagnostic value of serum carbohydrate-deficient transferrin might be more useful for identifying alcohol abuse than other widely available biochemical tests; however, its precise value as an indicator of chronic alcoholism is unclear. The main objective is to investigate the diagnostic significance of carbohydrate-deficient transferrin in chronic alcoholism in the Chinese population.In this study, we enrolled (1) 52 physically healthy subjects, (2) 20 patients with nonalcoholic liver disease, and (3) 70 alcoholics. Patients with liver injuries and a history of liver surgery were excluded. Serum gamma-glutamyltransferase, aspartate aminotransferase, alanine aminotransferase, and mean corpuscular volume were determined by standard biochemical assays, and serum carbohydrate-deficient transferrin was estimated in each group using capillary electrophoresis. Subsequently, the diagnostic value of carbohydrate-deficient transferrin (CDT) in chronic alcoholism was determined based on differences between each indicator among the three groups.The CDT level in the alcoholic group was significantly higher than that of the non-alcoholic liver disease and healthy control groups (P < .05). The area under the curve for alcoholism diagnosis was the highest for CDT, at 0.922, whereas those for gamma-glutamyltransferase, aspartate aminotransferase, alanine aminotransferase, and mean corpuscular volume were 0.860, 0.744, 0.615, and 0.754, respectively. When the cutoff value of CDT was set at 1.25%, the sensitivity and specificity were 85.5% and 89.6%, respectively. However, the correlation between CDT and daily alcohol consumption was weak (r = 0.175; P = .16).Compared with the other parameters evaluated, CDT was a better indicator of alcoholism. It should, therefore, be actively promoted in clinical practice. However, the correlation between CDT and daily alcohol consumption needs further evaluation.     

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

BACKGROUND: 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. METHODS: 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). RESULTS: 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). CONCLUSIONS: 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.     

缺糖转铁蛋白对酒精性肝病的诊断意义

目的 评价缺糖转铁蛋白（CDT）对酒精性肝病的诊断价值。方法 选择76例酒精性肝病,55例嗜酒者,32例非酒精性肝病和27例健康者,分别检测谷氨酰转肽酶（GGT）等肝功能指标和CDT。结果 酒精性肝病组CDT阳性率为93.4%;CDT诊断酒精性肝病的灵敏度为93.4%,特异性为71.9%,诊断价值高于GGT、丙氨酸转氨酶（ALT）和天冬氨酸转氨酶（AST）。结论 CDT是诊断酒精性肝病较理想的指标。     

Comparison of Different Methods for Detecting Carbohydrate-Deficient Transferrin

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 doubleantibody radioimmunoassay of collected fractions. Tf fractions with pl ± 5.7 were also measured by two different isoelectric focusing (IEF) methods, followed by immunofixation (SA-IEF-CDT and IEFCDT-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%, 67%, 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. The overall accuracy among alcoholics was similar using each of the methods tested. The same was true among heavy drinkers, although SA-IEF-CDT had the highest sensitivity and overall accuracy among this group, making the method slightly better than the other ones.     

植物凝集素亲和色谱层析法分离缺糖基转铁蛋白诊断酒精性肝病的临床研究

目的:观察酒精性肝病患者血清缺糖基转铁蛋白(CDT)水平变化,探讨CDT诊断酒精性肝病的临床价值.方法:应用植物凝集素亲和层析法分离血清CDT和正常转铁蛋白(Tf),然后应用ELISA技术分别测定酒精性肝病组患者及正常对照组人员CDT和Tf,最后计算CDT/Tf值.结果:两组人员血清植物凝集素亲和层析洗脱图谱均显示两个洗脱峰;CDT存在于第一洗脱峰,Tf存在于第二洗脱峰,ELISA定量结果显示:酒精性肝病组患者血清CDT平均水平为5.05±1.64,Tf平均水平为54.91±40.94,CDT/Tf值为0.123,正常对照组人员血清CDT平均水平为4.78±1.03,Tf平均水平451.61±241.37,CDT/Tf值为0.0117,经统计学分析,P＜0.05,差异有显著性意义.结论:酒精性肝病患者血清CDT水平及CDT/Tf值明显升高,CDT是诊断酒精性肝病良好的生化标志.     

Is Carbohydrate-Deficient Transferrin a Specific Marker for Alcohol Abuse? A Study in Patients with Chronic Viral Hepatitis

Carbohydrate-deficient transferrin, a transferrin isoform, is hailed as a new marker of chronic alcohol abuse, but its specificity is, however, not unequivocally accepted. The aim of the present study was therefore to determine carbohydrate-deficient transferrin levels in patients with chronic hepatitis B and C with or without documented chronic alcohol intake. Carbohydrate-deficient transferrin was measured using a double-antibody radioimmunoassay (CDTect^TM, Pharmacia®) in serum samples from 66 patients (45 males and 21 females; mean age: 39 years) with chronic viral hepatitis B ( n = 20) or C ( n = 46). Diagnosis of the underlying liver disease was established by liver biopsy. Carbohydrate-deficient transferrin levels were raised in 15 patients [23%; hepatitis B ( n = 2) and hepatitis C ( n = 13)]. In patients with chronic hepatitis B, the carbohydrate-deficient transferrin level was raised in two abstainers. In the 46 patients with chronic hepatitis C, 10 (22%) patients with an alcohol consumption of > 60 g/day for the men and 30 g/day for the women had raised carbohydrate-deficient transferrin levels. The overall specificity of carbohydrate-deficient transferrin for chronic alcohol abuse was thus 78%, suggesting an association between elevated carbohydrate-deficient transferrin levels and the presence of chronic viral hepatitis. Carbohydrate-deficient transferrin levels were not correlated with the histological grading or staging of chronic hepatitis B and C, or with biological markers of hepatic synthesis and cellular damage. Thus, an increased carbohydrate-deficient transferrin level may occur in patients with chronic viral hepatitis in the absence of chronic alcohol abuse. This fact should be kept in mind by physicians when using this marker to detect alcohol abuse.     

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

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

Carbohydrate Deficient Transferrin in Abstaining Patients With End-Stage Liver Disease

BACKGROUND: Carbohydrate deficient transferrin (CDT), a biochemical marker of chronic alcohol consumption, is used by researchers and clinicians alike in a variety of populations. Levels of CDT may be affected by certain types of medical illnesses and conditions. Thus the interpretation of CDT results may need to be carefully examined in these populations. Because CDT is synthesized, glycosylated, and secreted by the liver, the use of CDT values in patients with liver disease has been an area of focused interest. METHODS: We evaluated the CDT values of 79 abstaining patients with end-stage liver disease. These patients were recruited from a liver transplant clinic while they were listed and waiting for transplantation. Patients were determined to be abstaining both by interview and by random blood alcohol levels in those with a diagnosis of alcoholic liver disease. The severity of the liver disease was categorized by the Child-Pugh score. Correlations were determined between CDT values and liver enzymes, and Child-Pugh scores and liver diagnosis. RESULTS: Nearly 50% of the patients had a CDT value of 2.6% or above, indicating a clinically positive value. There were strong correlations between CDT and a number of biochemical and physical variables, most importantly the Child-Pugh score (r = 0.52, p = 0.000). Specific liver diseases were not associated with absolute CDT values. However, patients with hepatitis C (HCV) had a significantly higher chance of having a clinically positive CDT compared with patients with other types of liver diseases. CONCLUSIONS: These results suggest that an elevated CDT value may not accurately represent alcohol consumption in patients with advanced liver disease. In fact, in such patients, the CDT may become a marker for the degree of liver impairment in alcoholic and nonalcoholic liver disease. CDT values should be viewed with caution in any patient with liver disease especially when the degree of cirrhosis reaches a Child-Pugh score of C (total score of 10 or above).     

Immune Responses to Ethanol Metabolites and Cytokine Profiles Differentiate Alcoholics with or without Liver Disease

OBJECTIVES: Excessive alcohol consumption is associated with the generation of antibodies against neoantigens induced by ethanol metabolism. However, the associations between such immune responses, ethanol consumption, and liver injury remain unclear. METHODS: Eight-six male alcoholics with (n=54) or without (n=32) liver disease, and 20 male volunteers (6 abstainers, 14 moderate drinkers) underwent clinical, morphological, and biochemical assessments of liver status and ethanol consumption. RESULTS: Antiacetaldehyde adduct IgAs in both groups of alcoholics were significantly higher than those in the controls. Elevated IgGs occurred in patients with liver disease, whereas IgMs were high in the heavy drinkers without apparent liver disease. Liver disease patients had high levels of both proinflammatory (IL-2, IL-6, IL-8, TNF-alpha) and antiinflammatory (IL-10) cytokines, whereas those without liver disease showed elevated IL-6, IL-8, and IL-10 only. Ethanol consumption correlated significantly with antiadduct IgA and IL-6 levels, which also showed parallel changes upon abstinence. CONCLUSIONS: Alcoholic liver disease is associated with the generation of IgAs and IgGs against acetaldehyde-derived antigens and enhanced levels of both pro- and antiinflammatory cytokines, whereas elevated IgA, IL-6, and IL-10 characterize alcoholics without liver disease. These data suggest that immunological mechanisms may play a role in the sequence of events leading to liver disease in some patients with excessive drinking.     

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

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

Serum Carbohydrate-Deficient Transferrin as a Marker of Alcohol Consumption in Patients with Chronic Liver Diseases

We meesured serum levels of carbohydrate deficient transferrin (CDT) in 420 subjects: 100 healthy blood donors, 82 healthy employses, 70 abstaining patients with different chronic nonalcoholic liver disease, 16 abstaining patients with alcoholic fatty liver, 50 abstaining patients with alcohotic liver cirrhosls, 25 abusing patients with alcoholic fatty liver, 41 abusing patients with alcoholic liver cirrhosis, and 36 patients with alcohol dependence syndrome with a daily ethanol consumption of 173 ± 120 g the last 4 weeks before blood was drawn. In controls the serum level of CDT was significantly higher in females compared with males (17.7 ± 5.1 and 13.7 ± 3.8 units/liter, respectively), and the upper normal limit was defined as 27 and 20 units/liter. Sixty-two of 102 (60.8%) abusing patients with alcoholic liver disease had increased levels of CDT compared with 1 of 66 abstaining (1.5%) patients with alcoholic liver disease, and 10 of 70 (14.3%) abstaining patients with nonalcoholic liver disease among them 3 with primary biliary cirrhosis and 2 with chronic autoimmune hepatitis. No correlation was found between serum CDT and γ-glutamyltranspeptidase (GGT), AST, ALT, and mean red cell volume (MCV). The sensitivity and specificity for serum CDT was 61 and 92%, respectively, compared with 85 and 18% for GGT and 70 and 66% for MCV. No advantage was gained by using the CDT/transferrin ratio. Our study confirms that CDT is a specific marker for chronic alcohol abuse, except in few patients with other chronic liver diseases. Serum CDT seems to be a better indicator of abstention than GGT; AST and MCV in patients with alcoholic liver disease. However, in our hands CDT is not so sensitive for alcohol abuse in patients with liver disease as reported earlier in unselected alcoholics     

Sensitivity and Specificity of Carbohydrate-Deficient Transferrin as a Marker of Alcohol Abuse Are Significantly Influenced by Alterations in Serum Transferrin: Comparison of Two Methods

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.     

Carbohydrate-Deficient Transferrin Levels in a Female Population

Female college students ( n = 49) from a small southwestern United States university participated in the 9-month study. Data collected included the assessment of drinking habits and other related substance use habits and serum levels of carbohydrate-deficient transferrin (COT). Each subject provided an interview and blood sample on three occasions at 90-day intervals. Appended to the interview were a series of questions regarding stage of menstrual cycle and the diagnoses of certain diseases. The CDT values obtained were consistent with those obtained in other studies. Moderate-drinking subjects had significantly higher CDT values than did the abstainers and light drinkers. Females using oral contraceptives had significantly higher CDT values than those who were not taking oral contraceptives. Finally, although CDT values varied over time, they did not appear to vary as a function of menstrual cycle stage.     

Increases and Time-Course Variations in β-Hexosaminidase Isoenzyme B and Carbohydrate-Deficient Transferrin in Serum from Alcoholics Are Similar

β -Hexosaminidase B-isoforms ( β -hexosaminidase B, P, and intermediate forms; abbreviated herein as "Hex B") and serum carbohydrate-deficient transferrin (CDT) are two markers of alcohol abuse. In the present study, we have compared "Hex B" with CDT as markers of alcohol abuse in a group of alcoholics hospitalized for detoxification after a period of heavy alcohol abuse. We have also followed the disappearance rate of these two markers from circulation. "Hex B" was elevated in 38 of 42 patients hospitalized for detoxication, whereas CDT was elevated in 35 of 42 patients. A highly significant correlation was noted between "Hex B" and CDT in these patients ( p = 0.52, p < 0.001). Neither "Hex B" nor CDT correlated with γ-glutamyltransferase or AST. The disappearance rates from serum of "Hex B" and CDT were determined in 21 hospitalized patients followed for up to 15 days. "Hex B" and CDT showed similar time-course variation and half-lives, 6.5 ± 3.7 (mean × sd ) and 8.6 ± 4.1 days, respectively. The possible reasons for a relation between these two markers are discussed, and it is concluded that more experience of both "Hex B" and CDT in unselected populations is needed to establish the diagnostic potential of these tests as markers of alcohol abuse.     

CDT by Anion-Exchange Chromatography Followed by RIA as a Marker of Heavy Drinking Among Men

Carbohydrate-deficient transferrin, CDT, had previously been reported to be an excellent marker for alcoholism. The present population-based study examined the diagnostic value of CDT among consecutive middle-aged males including 122 social drinkers (mean alcohol consumption 88 ± 79 g per week) and 77 non-alcoholic heavy drinkers (301 ± 195 g/wk). Ninety-six men with a well-documented history of chronic alcoholism (≥1000 g/wk) were used as a reference group. The CDT (containing mainly isotransferrin with pl = 5.8 and 5.9) was separated by anion exchange chromatography and assayed by RIA. The CDT values of social drinkers (mean ± SD = 14 ± 5 U/I) were significantly lower than those of heavy drinkers (19 ± 13 U/I, p < 0.01) and alcoholics (34 ± 18 U/I, p < 0.001). In the whole material CDT correlated positively with alcohol consumption ( r = 0.53, p < 0.001). At a specificity of 91.8%, CDT found 28.6% of the heavy drinkers and 79.2% of the alcoholics; the best traditional marker, GGT, with a specificity of 86.9%, found 35.1% and 64.6%, respectively. In conclusion, CDT is a specific marker, which is superior to traditional markers for identifying alcoholics. Unfortunately, it does not seem to provide additional power for identifying the important group, non-alcoholic heavy drinkers.     

Decrease in Cytochrome P4502E1 as Assessed by the Rate of Chlorzoxazone Hydroxylation in Alcoholics during the Withdrawal Phase

To evaluate cytochrome P4502E1 (CYP2E1) induction in alcoholics, the ratio of the concentrations of 6-hydroxychlorzoxazone (6-OH-CHZ) and chlorzoxazone (CHZ) was measured in blood 2 hr after CHZ ingestion using a HPLC method. This ratio was determined in controls and in alcoholic patients after 1, 2, 3, 4, 5, 8, and 21 days withdrawal. It was found to be 0.34 ± 0.03 in 30 controls and 1.05 ± 0.14 in 41 alcoholic patients within 2 days following ethanol withdrawal. This ratio decreased rapidly during withdrawal as attested by the short half-life of CYP2E1, which was found to be 2.5 days. Patients tested for CHZ metabolism after 8 or 21 days alcohol abstinence displayed the same ratio as controls [0.35 ± 0.03 ( n = 28) and 0.31 ± 0.03 ( n = 34), respectively]. No correlation was observed between γ-glutamyltransferase, carbohydrate-deficient transferrin values, the amount of alcohol consumed/day, and the 6-OH-CHZ/CHZ ratio. There was no influence of smoking on the rate of CHZ hydroxylation, because smokers displayed the same ratio as nonsmokers [0.33 ± 0.025 ( n = 62) and 0.33 ± 0.02 ( n = 30), respectively]. The CHZ hydroxylation ratio seems to be a good reflection of the hepatic and extrahepatic CYP2E1 activity in humans.     

Combining Ondansetron and Naltrexone Treats Biological Alcoholics: Corroboration of Self-Reported Drinking by Serum Carbohydrate Deficient Transferrin, A Biomarker

BACKGROUND: Recently, we showed by using self-report that combining ondansetron (4 microg/kg twice a day) and naltrexone (25 mg twice a day) was effective at reducing drinking and increasing abstinence among early-onset alcoholics (EOAs), who are characterized by a range of antisocial behaviors and high biological and familial disease predisposition. Here, we investigated whether the self-reported differences in drinking would be corroborated by measurements of serum carbohydrate-deficient transferrin (CDT) level, a sensitive, reliable, and well-validated marker of transient alcohol consumption. METHOD: An 8-week double-blind clinical trial was performed in which 20 EOAs were randomized to receive ondansetron (4 microg/kg twice a day) and naltrexone (25 mg twice a day) or placebo as an adjunct to weekly standardized cognitive behavioral therapy. Serum CDT was assessed at weeks 0 (baseline), 4, and 8. RESULTS: Log serum CDT was significantly lower in the ondansetron and naltrexone group (group mean, 1.44 +/- 0.076) compared with the placebo group (group mean, 1.82 +/- 0.113), as evidenced by a main effect of group [F(1,15) = 7.2, p = 0.017; effect size = 0.32], visit [F(1,16) = 11.2, p = 0.004; effect size = 0.41], and an interaction between group and visit [F(1,16) = 27.54, p < 0.001; effect size = 0.63]. CONCLUSIONS: The combination of ondansetron plus naltrexone was superior to placebo at reducing serum CDT. This corroborated our self-reported drinking data and demonstrated that the medication combination is an effective treatment for EOAs.     

Utility of Carbohydrate-Deficient Transferrin as a Marker of Relapse in Alcoholic Patients

Carbohydrate-deficient transferrin (CDT) has been proposed as a marker of alcoholism. However, its role in monitoring alcoholic patients for relapse has not been extensively studied. We therefore performed sequential serum CDT measurements using a microcolumn/radioimmunoassay method (Kabi Pharmacia, Piscataway, NJ) in 86 male alcoholics participating in a hepatitis vaccination program who were monitored for relapse using self-report and collateral history (when available). The maximum serum CDT was significantly higher in patients who relapsed (n = 38) (33.1 ± 3.1 mg/liter), as compared with abstinent subjects with collateral verification ( n = 39) (18.8 ± 1.3, p < 0.001) and abstinent patients without collateral verification ( n = 9) (17.4 ± 1.3, p < 0.01). Using the manufacturer's currently recommended threshold of 20 mg/liter for males, serum CDT was elevated in 29 of 38 patients who relapsed (sensitivity 76.3%). In 16 (42.1%) of the relapsed patients, a serum CDT above this threshold preceded the patient's self-report by at least 28 days. However, serum CDT exceeded 20 mg/liter in 10 of 48 patients who remained sober (specificity 79.2%); three of these patients had clinical and/or pathological evidence of cirrhosis. Using a threshold of 25 mg/liter, 21 of 38 patients who relapsed had an elevated serum CDT (sensitivity 55.3%); 12 (31.6%) of these patients had elevated serum CDT before self-report. Only 4 of 48 subjects who remained sober had serum CDT levels that exceeded 25 mg/liter (specificity 91.7%); three of these patients had clinical and/or pathological evidence of cirrhosis. In conclusion, serial serum CDT testing detects relapses before self-report in male subjects. Values between 20–25 mg/liter suggest relapse, but call for collateral verification, whereas CDT values above 25 mg/liter are usually diagnostic of relapse in the absence of cirrhosis.     

Carbohydrate-deficient transferrin and gamma-glutamyltransferase for the detection and monitoring of alcohol use: results from a multisite study

BACKGROUND: The purpose of this article is to evaluate the biological marker of heavy alcohol use, carbohydrate-deficient transferrin (CDT), in contrast to the older and more widely used gamma-glutamyltransferase (GGT) for the detection and monitoring of heavy alcohol use. METHODS: In this report, CDT and GGT sensitivity and specificity for heavy alcohol intake are examined in a large multisite study in which 444 recently admitted inpatient alcoholics were compared with 204 matched social drinker controls. In addition, changes in these biomarkers were evaluated during an initial abstinence period and biweekly over 14 weeks of monitoring to compare changes in CDT and GGT during continued abstinence or relapse. RESULTS: CDT and GGT were comparable in identifying heavy alcohol consumption in men, but GGT appeared to be better for women. For both genders, when these markers were combined, there was better sensitivity than when used alone. CDT and GGT both decreased during 4 weeks of abstinence. When we used a 30% increase from baseline abstinent levels as an indicator, CDT appeared marginally better than GGT at indicating relapse in men but not in women. For men in particular, relapse over the course of the study was best identified by evaluating changes (30% increase) in both markers simultaneously. CONCLUSIONS: These results support the utility of CDT, especially when used in conjunction with GGT, as an aid in detecting and monitoring heavy alcohol consumption.