Comparison of carbohydrate-deficient transferrin, immunoglobulin A antibodies reactive with acetaldehyde-modified protein and acetaldehyde-modified albumin with conventional markers of alcohol consumption

Carbohydrate-deficient transferrin (CDT) has emerged as the best new marker for alcohol abuse. Recently plasma immunoglobulin A (IgA) reactivity with acetaldehyde (AcH)-modified proteins, or the modified proteins per se, have been proposed as a markers for high levels of alcohol consumption. In this study, we have compared CDT, IgA reactivity with AcH adducts (IgA ASR), and AcH-modified albumin with conventional markers of high alcohol intake in groups with well-defined drinking histories. The plasma activity of ALT, AST, and gamma-glutamyltransferase increased steadily with increasing alcohol consumption. CDT and AcH-modified albumin showed a similar pattern, whereas IgA ASR appeared only to be elevated after a threshold level of consumption had been reached. Neither CDT IgA ASR or AcH-modified albumin correlated strongly with any of the conventional markers or each other. This study shows that CDT, IgA ASR, AcH-modified albumin, and the conventional markers are not related, but suggests that the concurrent use of CDT and IgA ASR may lead to better identification of high alcohol intake.     

Carbohydrate deficient transferrin and other markers of alcohol consumption in the general hospital

BACKGROUND: The ascertainment of patients who consume important amounts of alcohol admitted to a hospital is essential to prevent medical and psychological complications. Carbohydrate deficient transferrin (CDT) is a new marker of alcohol consumption which requires validation in the hospital setting. METHODS: The values of carbohydrate deficient transferrin (CDT), glutamic oxalacetic transaminase (GOT), gamma glutamil transpeptidase (GGT) and mean corpuscular volume (MCV) were measured in 101 consecutive patients admitted to the Internal Medicine and Surgery Departments. Considering amounts higher than 60 g/day of ethanol for male patients and higher than 40 g/day for female patients as risk consumption, the values for sensitivity, specificity and area under the curve were calculated for the different biological tests. RESULTS: Twenty-six percent of patients reported a consumption of risk. The sensitivity of the tests were lower than 50% and specificities higher than 77%. CDT had the lowest sensitivity (15%) but it was very specific (98%). CDT had a better sensitivity among women than among men. None of the tests had an area under the curve with adequate efficiency levels. CONCLUSIONS: CDT among the hospitalized patients and other biological markers of alcohol consumption have a low efficiency.     

Prognostic value of some biochemical and immunologic factors in the management of multiple myeloma

The aim of this study was to measure serum carbohydrate-deficient transferrin (CDT) in consecutive patients attending a general medical clinic with a range of alcohol intakes to determine its value in assessing such intake. Eighty-one consecutive patients (42 male, 39 female) aged 20-85 years (median = 49.5 years) attending an out-patient clinic were selected for the study. Each patient completed an alcohol diary detailing the units of alcohol consumed in the previous week, a CAGE questionnaire and an alcohol history, and underwent conventional blood tests including mean corpuscular volume (MCV), liver function tests, and gamma-glutamyl transferase (GGT). CDT was estimated using an enzyme immunoassay (CDTect, Pharmacia). The group comprised of 17 teetotallers, 28 light (<100 g/week), 23 moderate (100-400 g/week), and 13 heavy (>400 g/week) drinkers. Median serum CDT for heavy drinkers (25.5 U/l) was significantly higher than for the rest (median = 17 U/l, Kruskal-Wallis test, P = 0.01). Serum CDT correlated significantly with the CAGE score (Mann-Whitney test, P = 0.01), but poorly with alcohol diary records (r = 0.1, P = 0.4). However the correlations between GGT and diary records (r = 0.43, P = 0.001) and MCV with diary records (r = 0.5, P < 0.001) were significant. Sensitivity, specificity, and positive predictive value for elevated serum CDT were 69, 81 and 41% respectively in detecting heavy drinking. The positive predictive values for the various parameters were 43% for elevated serum GGT, 41% for raised erythrocyte MCV, and 75% for a positive score on the CAGE questionnaire. When a combination of the markers CDT, GGT, and MCV was used, elevation in two of the three markers detected heavy drinking with sensitivity of 85%, specificity of 88%, and positive predictive value of 61%. We conclude that, in out-patients with a wide range of alcohol intakes conventional markers such as serum GGT and erythrocyte MCV were more suitable than serum CDT for assessing alcohol intake. Serum CDT when used in combination with serum GGT and erythrocyte MCV was useful in detecting heavy drinking. The importance of careful history-taking including a standardized questionnaire is emphasized.     

Utility of biological markers during outpatient treatment of alcohol-dependent subjects: carbohydrate-deficient transferrin responds to moderate changes in alcohol consumption

A group of 25 alcohol-dependent subjects in outpatient treatment were monitored for a period of 4 weeks. They were weekly interviewed for their alcohol consumption and their serum levels of carbohydrate-deficient transferrin (CDT) and gamma-glutamyltransferase (GT) were analyzed. The majority of the patients reported an excessive and fairly constant alcohol intake during the observation period. When selecting those patients that reported periods of 1 or 2 weeks with moderate changes in alcohol consumption, corresponding changes in CDT were demonstrated. Thus, of 14 patients reporting an increased alcohol consumption for 2 weeks (mean values increased from 57 to 101 g/day), 11 showed an increase in CDT at the end of the period. The mean CDT value of all 14 increased from 5.5 to 6.7% (p < 0.05). Slight, but not significant, increases were noted in GT, indicating that CDT is more sensitive than GT in detecting increased alcohol consumption. Furthermore, of 17 patients that reported decreased alcohol consumption for one or several weeks, 14 showed decreased CDT and GT values. The mean values of all 17 were reduced from 5.1% to 4.5% (CDT) and from 126 units/liter to 97 units/liter (GT) (p < 0.05 for both parameters). The results indicate that CDT responds to moderate changes in alcohol consumption in alcohol-dependent patients and may thus be useful as a corrective tool to self-reports of alcohol consumption during outpatient treatments.     

Carbohydrate-deficient transferrin is associated with insulin sensitivity in hypertensive men

An elevated concentration of carbohydrate-deficient transferrin in serum (CDT) has been reported to indicate excessive ethanol consumption. However, in hypertensive men, we found low values for diagnostic sensitivity and specificity. Furthermore, in the individuals with high CDT values, the concentrations of serum triglycerides and blood glucose were low rather than high, indicating that factors related to insulin/glucose metabolism may be operative. The current study addresses this issue by examining 48 patients with treated hypertension and at least 1 of following: hypercholesterolemia, history of smoking, and diabetes mellitus. We determined serum CDT, fasting plasma insulin, and glucose disposal rate during hyperinsulinemic euglycemic clamp. Seven patients had elevated CDT concentrations. This group of patients had higher glucose disposal rates than the others (mean difference, 19 mumol/min.kg lean body mass; 95% confidence interval, 5-33 mumol/min.kg lean body mass; P = 0.0096), but did not differ in body mass index or alcohol intake. Serum CDT correlated positively with glucose disposal rate (r = 0.55; P = 0.0004) and negatively with fasting plasma insulin (r = -0.43; P = 0.0039). These relationships remained after exclusion of 8 patients with diabetes mellitus and adjustment for potentially confounding factors. We conclude that the serum CDT concentrations in our patients were associated with insulin sensitivity.     

Effects of alcohol on sympathetic activity, hemodynamics, and chemoreflex sensitivity

Alcohol intake has been shown to worsen obstructive sleep apnea and increase nocturnal hypoxemia. The mechanisms of this action are unclear. Animal studies suggest that a reduction in chemoreflex sensitivity may be implicated. Using a double-blind, randomized, vehicle-controlled design, we tested the hypothesis that oral alcohol intake depresses chemoreflex sensitivity in humans. We examined the effects of oral alcohol intake (1.0 g/kg body wt) on blood pressure, heart rate, heart rate variability, muscle sympathetic nerve activity, forearm vascular resistance, and minute ventilation in 16 normal male subjects. Peripheral and central chemoreflex sensitivity were measured in response to hypoxia (n = 10) and hypercapnia (n = 6), respectively. Plasma alcohol increased from 0 to 23.2 +/- 1.5 mmol/L (107 +/- 7 mg/dL) at 60 minutes and 20.2 +/- 1 mmol/L (93 +/- 4 mg/dL) at 85 minutes after alcohol intake (P < .0001). Alcohol induced an increase in heart rate from 59 +/- 2 to 66 +/- 2 beats per minute (P < .01) and increased the ratio of low- to high-frequency variability of heart rate (P < .05). Although alcohol increased sympathetic nerve activity by up to 239 +/- 22% of baseline values (P < .01), forearm vascular resistance after alcohol was lower than that after vehicle (P < .05). Blood pressure did not increase compared with the vehicle session. Oxygen saturation during hypoxia after alcohol was 4 +/- 1% lower than it was during hypoxia after vehicle (P < .05) although arterial blood PO2 was unchanged. Alcohol did not affect the cardiovascular, sympathetic, or ventilatory responses to either hypoxia or hypercapnia. Acute increases in plasma alcohol increase heart rate and sympathetic nerve activity; blood pressure is not increased, probably because of vasodilator effects of alcohol. Alcohol does not alter chemoreflex responses to hypoxia or hypercapnia; thus, alterations in chemoreflex sensitivity are unlikely to explain the effects of alcohol on sleep apnea. Alcohol may reduce the affinity of hemoglobin for oxygen.     

Carbohydrate-deficient transferrin: a new biochemical marker for chronic excessive alcohol consumption

OBJECTIVE: To assess the usefulness of the biochemical marker 'carbohydrate deficient transferrin' (CDT) in relation to conventional markers for chronic excessive alcohol use. DESIGN: Prospective. SETTING: Addiction clinic Paschalis, Wanssum, the Netherlands. METHOD: Addicts for weaning (n = 125) were questioned at admission about their drinking habits in the last two weeks. Based on the criterion more or less than 60 g alcohol per day, the group was divided into excessive and nonexcessive alcohol users (men: 52 abusers, 51 non-abusers; women: 12 abusers, 10 non-abusers). Mean cell volume (MCV), gamma-glutamyl transpeptidase (gamma GT) and total transferrin were measured in blood collected 2 days after admission, as well as CDT by two methods (CDTect and % CDTriTIA). RESULTS: In men the CDTect test was the most sensitive: sensitivity 82% with specificity 88%. The sensitivity and specificity were 62% and 86% for gamma GT, 50% and 95% for % CDTriTIA, and 34% and 98% for MCV. The combination of a positive CDTect result and a positive gamma GT result gave a predictive value of use of alcohol > 60 g/day of 100%. The results of CDT and gamma GT were also used for a logistic regression model, giving a statistical prediction for excessive alcohol use. The subgroups of women were too small to detect statistical significant differences between tests. CONCLUSION: The CDTect test was more sensitive for the detection of chronic excessive alcohol use than the conventional markers. The combination of gamma GT and CDTect results increased the positive predictive value.     

Analysis of carbohydrate deficient transferrin by capillary zone electrophoresis

We report a capillary zone electrophoresis method to separate the various sialylated isoforms of transferrin. The separation is carried out under nondenaturing conditions and at basic pH. Under these conditions, transferrin exhibits two major and three minor peaks. Plasma samples from a population consuming varying amounts of alcohol at different intervals were studied. A cut-off value of 3% carbohydrate deficient transferrin (CDT: disialo, monosialo, and asialo transferrin), results in a clinical sensitivity of 88% in a population consuming at least 70 g/day alcohol for a minimum of two weeks. The sensitivity dropped significantly in a population consuming less than 70 g/day. This confirms previous reports of CDT as a specific marker for significant and chronic use of alcohol. Capillary electrophoresis offers an alternative method with respect to analysis time and throughput in the clinical laboratory.     

Carbohydrate-deficient transferrin: diagnostic efficiency among patients with end-stage liver disease before and after liver transplantation

We tested the diagnostic validity of carbohydrate-deficient transferrin (CDT) as an indicator for relapse into elevated alcohol consumption among patients who were examined under follow-up treatment before (n = 147) and after (n = 102) orthotopic liver transplantation (OLT) in the outpatient-department of the University Hospital Department of Surgery in Hamburg-Eppendorf. CDT measurements were performed with two commercial kits in parallel (CDTect-RIA and CDT%-RIA). Short-term parameters of alcohol consumption (ethanol, methanol) indicated relapses into elevated alcohol consumption in 11.4% of the evaluated patients with alcoholic liver disease (ALD) before transplantation. Before OLT, median CDT values were determined to be elevated among patients with alcoholic as well as nonalcoholic end-stage liver diseases (NALD). Among patients with ALD, we found elevated CDT medians even in those who were successfully scheduled for OLT after long-term evidence of abstinence proved by biochemical short-term parameters and psychological tests. Both CDTect and CDT% assays had comparable low specificities in selected patient groups before transplantation. CDT% and CDTect were negatively correlated with the albumin level. Before the study ended, CDT was no longer implemented in the evaluation of whether an OLT should be administered. This was due to inconsistent results of CDT in ALD as well as NALD. After OLT, patients with ALD, as well as NALD, had statistically significant lower CDT medians than before OLT, which ranged within reference levels. We determined, according to CDT, elevated alcohol consumption subsequent to OLT in 4 of 13 patients with ALD who underwent transplantation during the study (median observation period: 10 months). CDT does not appear to be useful in evaluating patients before OLT. With regained specificity and high sensitivity in patients after OLT, CDT could be recommended as a standard instrument for quality control in patients with ALD after liver transplantation.     

Phosphatidylethanol in blood as a marker of ethanol consumption in healthy volunteers: comparison with other markers

Phosphatidylethanol is a "pathological" phospholipid, formed via the action of phospholipase D only in the presence of ethanol. The present study was made to elucidate how different levels and patterns of alcohol intake affect blood levels of phosphatidylethanol in comparison with other markers of abuse. We used a new HPLC-evaporative light-scattering detection technique for phosphatidylethanol quantitation. This method had a total coefficient of variation of <20% at the detection limit of 0.2 nmol, equaling 0.8 micromol/liter of whole blood. Two groups were studied. (a) Five healthy volunteers were given 32 to 47 g of ethanol in a single dose, to give blood ethanol levels of approximately 25 mmol/liter after 30 to 60 min. Phosphatidylethanol, carbohydrate-deficient transferrin (CDT), and blood ethanol were measured before and after the intake. (b) Twelve student volunteers were studied during a 3 week period of prolonged alcohol consumption (total estimated intake: 1334 +/- 488 g, mean +/- SD) and phosphatidylethanol, serum-CDT, gamma-glutamyltransferase, and blood ethanol were measured at the start of the period (day 1) and twice at the end of the period (days 18 and 21). In group (a), no phosphatidylethanol was detected at any time after ethanol dosage/intake. In group (b), no blood phosphatidylethanol or blood ethanol could be demonstrated at the start, and serum-CDT was below the discrimination limit (1.3%) in all persons. No phosphatidylethanol was detected in those four persons with the lowest intake (742 +/- 150 g). However, the remaining eight persons had detectable levels of phosphatidylethanol (1.0 to 2.1 micromol/liter), and these had a higher total intake (1630 +/- 389 g). There was a statistically significant (p = 0.02) increase in serum CDT for 3 weeks. However, only 3 of 12 persons increased above the discrimination limit. The present results indicate that a substantial alcohol intake is needed to elevate blood phosphatidylethanol. In comparison with serum-CDT, blood phosphatidylethanol appears more sensitive.     

Comparison of serum beta-hexosaminidase isoenzyme B activity with serum carbohydrate-deficient transferrin and other markers of alcohol abuse

We have compared beta-hexosaminidase (beta-Hex) activity, carbohydrate-deficient transferrin (CDT), mean corpuscular volume (MCV), gamma-glutamyltransferase (GGT), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) values in serum from male alcoholic patients with the corresponding values in moderate and non-drinking subjects. The total beta-Hex activity was 2.5 times higher in the alcoholics than in the moderate drinkers and this increase was mainly due to a 5-fold increase in the activity of the B-isoform of the enzyme. This was expressed as a percentage of the total beta-Hex activity and called 'beta-Hex B%'. Strong correlations were found between alcohol consumption (g/ day) and beta-Hex B% (r = 0.757, P < 0.001, n = 42), alcohol consumption and CDT (r = 0.671, P < 0.001, n = 42), and beta-Hex B% and CDT (r = 0.628, P < 0.001, n = 57). Serum beta-Hex B% had a sensitivity of 94% and a specificity of 91% in detecting alcoholic drinking of > 60 g/day. As a single marker of alcoholic drinking, it was markedly more sensitive than MCV and the liver enzymes GGT, AST and ALT, and slightly more sensitive than serum CDT (94 vs 83%). At the CDT cut-off level of 20 U/l, 17% of the moderate and non-drinkers would have been classified as alcoholic drinkers and 17% of the alcoholics would have been classified as moderate drinkers. Some of these misclassifications were eliminated if the beta-Hex B% results were taken into account. We suggest that serum beta-Hex B% can be a useful and inexpensive laboratory test for alcohol abuse.     

Usefulness of carbohydrate-deficient transferrin in alcohol-elated problems

BACKGROUND: Carbohydrate-Deficient Transferrin (CDT) is a new marker for excessive alcohol drinking. It appears to be useful to detect alcoholism, harmful consumption and relapse. It have been introduced in our country recently. METHOD: Recent studies about utility of CDT have been reviewed. RESULTS: Sensitivity and specificity of CDT level as a marker of alcoholism were 72-97% and 31-81% respectively. As a marker of harmful consumption its sensitivity was 15-69% and its sensitivity was higher than 82%. CDT was demonstrated to be a effective maker for evaluating alcoholic abstinence in alcoholic patients. CONCLUSIONS: CDT determinations have a high specificity for screening heavy drinking in different settings. Problems related to its sensitivity are discussed.     

Does carbohydrate-deficient transferrin predict the severity of alcohol withdrawal syndrome?

Alcohol withdrawal often causes severe complications. However, many addicts deny any abuse. Thus, the diagnosis of alcohol abuse frequently becomes difficult. Laboratory parameters are often used to support the diagnosis of alcohol abuse. Furthermore, laboratory parameters should facilitate the prediction of the severity of alcohol withdrawal syndrome (AWS). The most promising laboratory parameter indicating a recent elevated alcohol consumption is carbohydrate-deficient transferrin (CDT). The aim of this study was to examine whether the measurement of CDT at admission can indicate a higher risk for the development of a complicated AWS. The severity of AWS was assessed by the AWS scale, consisting of two subscales for somatic and mental symptoms. CDT was measured by different methods (radioimmunoassay and HPLC). The radioimmunoassay for CDT (CDTect) yielded the best prediction. Our results showed a weak correlation between CDTect and the severity of AWS. However, there were great gender differences. In men, CDTect had the highest positive predictive value for a severe AWS (86.7%), whereas in women mean corpuscular volume was the best predictor (77.8%). However, the sensitivity of CDTect in men (25.5%), as well as mean corpuscular volume in females (29.2%), was too low for a screening test in a general hospital.     

Evaluation of the efficacy of naltrexone in alcoholism by the determination of serum carbohydrate-deficient transferrin

Naltrexone (NTX) has been shown to be a useful drug for the treatment of alcohol dependence (AD). Carbohydrate-deficient transferrin (CDT) in serum is a new biologic marker of alcohol abuse. To evaluate the efficacy of NTX (50 mg/d) in AD, a group of 20 alcoholics with CDT > 20 U/l was studied using monthly laboratory tests (CDT, ESR, AST, ALT, GGT) and specific psychological testing (CAGE). After the second month statistically significant differences in CDT levels were found. By the end of the study, 13 patients (responders) had normalized their CDT levels. There was no correlation between CDT values and the other laboratory markers. The difference in routine laboratory markers between responders and non responders was not significant. NTX was well tolerated by all the patients and significant alcohol abstinence was achieved. CDT was demonstrated to be a effective marker for the evaluation of alcoholic abstinence during treatment with NTX. Superior results were obtained in comparison with the routine customary markers for AD.     

The effect of drinking intensity and frequency on serum carbohydrate-deficient transferrin and gamma-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.     

A case-control study of single and multiple stomach cancers in Saitama Prefecture, Japan

A case-control study of stomach cancer was done in Saitama Prefecture, Japan, in relation to dietary, smoking, and drinking habits. The study was based on two sets of cases (216 male single and 35 male multiple stomach cancer cases newly diagnosed and of adenocarcinoma type), and 483 male controls derived from residents of Saitama Prefecture. Dietary habits were investigated for the intake of 12 separate foods and 12 food groups by means of a food frequency questionnaire, including individual taste preferences. Among the single stomach cancer series, dose-response relationships were observed for 7 dietary items (preference for salty foods, miso soup, boiled fish, pickled vegetables, nuts, raw vegetables, and seaweed) in the multiple logistic regression analysis. As for the multiple stomach cancer case series, dose-response relationships were observed for 3 dietary items (miso soup, fruits, and seaweed) in the multiple logistic regression analysis. Cigarette smoking and alcohol use were not significantly related to the risk of either single or multiple stomach cancer.     

Serotonin and alcohol intake, abuse, and dependence: findings of animal studies

Despite a relatively large body of literature on the role of the neurotransmitter serotonin (5-hydroxytryptamine, or 5-HT) in the regulation of alcohol intake, the functional significance of serotonergic neurotransmission and its relationship to alcohol intake, abuse, and dependence remains to be fully elucidated. In part two of this review, the experimental (animal) data is summarized along two lines: the effects of serotonergic manipulations on the intake of alcohol, and the effects of acute and chronic alcohol intake, as well as the withdrawal of chronic alcohol, on the serotonergic system. It is concluded that serotonin mediates ethanol intake as a part of its larger role in behavior modulation, such that increases in serotonergic functioning decrease ethanol intake, and decreased serotonergic functioning increases ethanol intake. Ethanol produces transient increases in serotonergic functioning that activate the mesolimbic dopaminergic reward system. The results are discussed in light of recent theories describing the regulatory role of serotonin in general behavior.     

Attenuation of alcohol intake by ibogaine in three strains of alcohol-preferring rats

Alcohol-preferring (P), Fawn-Hooded (FH) and alcohol-accepting (AA) rats were injected intraperitoneally (IP) or subcutaneously (SC) with different doses (10, 30, and 60 mg/kg) of Ibogaine or vehicle. In a separate experiment, FH rats were administered intragastrically (IG) with either 60 mg/kg of Ibogaine or vehicle for 5 days. In addition, the effects of Ibogaine on blood alcohol concentrations were measured. Our data show that, contrary to the SC administration of Ibogaine, IP administration of the agent significantly and dose-dependently reduced alcohol intake in these rats. Subchronic IG administration of 60 mg/kg of Ibogaine into FH rats significantly reduced alcohol intake without the development of tolerance or a significant effect on food or water intake. A single IP injection of 60 mg/kg Ibogaine into FH rats did not affect the blood alcohol levels. These results show that Ibogaine when injected IP or IG, but not SC, can significantly reduce alcohol intake without an effect on blood alcohol concentrations or food intake. These findings may suggest the involvement of Ibogaine's metabolite(s) in reducing alcohol intake. Although the neuronal mechanism(s) of action of Ibogaine on the regulation of alcohol intake is not fully understood, it is speculated that Ibogaine or its metabolite(s) exerts its attenuating effect on alcohol intake by modulating neurotransmitters/neuromodulators proposed to be involved in regulation of alcohol consumption.     

Reproductive function and contraception in the postpartum period

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, gamma-glutamyl transpeptidase, iron, transferrin and assessment of the liver iron concentration by magnetic resonance imaging. 11 patients were re-examined during iron depletion with phlebotomies. 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/l to 16.6 (SD 7.2) U/l (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 concentration and serum CDT in the patients not on 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.     

Moderate alcohol consumption and loss of cerebellar Purkinje cells

OBJECTIVE: To examine the dose-response effect of alcohol consumption on the number of cerebellar Purkinje cells. DESIGN: A prospective necropsy study combined with detailed reports on use of alcohol from a relative or friend. The number of Purkinje cells was counted in the anterior midsagittal section of the cerebellar vermis, the area of which was measured by computer assisted morphometry. SETTING: Department of forensic medicine, University of Helsinki. SUBJECTS: 66 men, aged 35 to 69 years, subjected to medicolegal necropsy because of sudden or violent death. The average all year daily alcohol consumption over the year was 0 to 10 g in 17 men, 11 to 80 g in 24 men, and more than 80 g in 25 men. MAIN OUTCOME MEASURES: Number of Purkinje cells, alcohol consumption. RESULTS: The numbers and density of Purkinje cells in the cross section of vermis showed a consistent but weak decrease with increasing daily alcohol intake but not with age. A wide variation in the cell counts was observed, especially in men drinking more than 80 g, suggesting differences in the susceptibility to effects of alcohol. Compared with men drinking 40 g or less, a long term moderate consumption of an average of 41 to 80 g daily was associated with a significant average loss of 242 (95% confidence interval 45 to 439) Purkinje cells (15.2%) from a mean of 1583 to 1341 cells. In those drinking 81 to 180 g the average loss was 535 (259 to 811) cells (33.4%) to a mean of 1048 cells. The density of cells in the cross section of vermis also fell significantly by 0.9 cell/mm (0.1 to 1.7) when the daily consumption exceeded 40 g and by 1.4 cell/mm (0.3 to 2.5) when the intake was 81 to 180 g. Only three cases (4.5%) in the series showed macroscopical cerebellar atrophy. CONCLUSION: Long term intake of moderate doses of alcohol daily for 20-30 years may damage the cerebellum before the onset of macroscopical atrophy. Despite distinct individual differences an all year average daily alcohol intake of 41-80 g results in a risk of significant loss of Purkinje cells.