Carbohydrate-Deficient Transferrin and γ-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 γ-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 simuttaneously, 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. Because serum CDT and GGT levels appear to be independently associated with heavy alcohol consumption, their combined measurement should increase the sensitivity of detection of this condition.     

Boronate Affinity Chromatography of γ-Glutamyltransferase in Patients with Hepatocellular Carcinoma

We analyzed the serum gamma-glutamyltransferase (gamma-GT) by boronate affinity chromatography to ascertain the presence or absence of any changes in the binding properties of gamma-GT toward boronate gels in patients with hepatocellular carcinoma and liver cirrhosis, and in normal controls. The mean gamma-GT activity ratio of the bound (peak 2) and nonbound (peak 1) fraction in patients with hepatocellular carcinoma was significantly higher than that in patients with liver cirrhosis or in normal controls. Thus, the gamma-GT, which has adjacent cis-hydroxyl groups in its carbohydrate moieties, was found to increase in the serum of patients with hepatocellular carcinoma. The positivity rate was examined in patients with hepatocellular carcinoma and liver cirrhosis, using a cut-off level for the peak 2:peak 1 ratio of 1.05 (mean + 2 SD of liver cirrhosis). Nineteen (42.2%) patients with hepatocellular carcinoma had a ratio of peak 2:peak 1 higher than 1.05. Nine of the 19 patients who had serum alpha-fetoprotein levels below 100 ng/ml had an elevated peak 2:peak 1 ratio. In total, 77.8% of the occurrence of hepatocellular carcinoma could be detected by a combination of these two markers. Three patients who had developed hepatocellular carcinoma during the course of cirrhosis but remained negative for alpha-fetoprotein throughout the course developed higher levels of peak 2:peak 1 ratio when hepatocellular carcinoma occurred. These results indicate that the two markers, the peak 2:peak 1 ratio of serum gamma-GT activity and serum alpha-fetoprotein level, may be considered to serve as complementary markers for the diagnosis of hepatocellular carcinoma.     

Influence of Age and Body Mass Index on γ-Glutamyltransferase Activity: A 15-Year Follow-Up Evaluation in a Community Sample

Most clinicians and researchers view serum γ-glutamyltransferase (GGT) activity as a measure that can be interpreted equally in patients regardless of their demography. The present study evaluates the concurrent influence of age and body mass index (BMI) on GGT in a sample of 133 high functioning young men, with detailed assessment of the pattern of alcohol use at ages 20 [time 1 (T1)], 30 [time 2 (T2)], and 35 [time 3 (T3)]. GGT increased between T1 and T2 (15.4 ± 9.65 units/liter vs. 20.1 ± 12.07 units/liter, t = 4.17, p < 0.001), and between T2 and T3 (20.1 ± 12.07 units/liter vs. 27.3 ± 24.69 units/liter, t = 4.11, p < 0.001). Controlling for drinking quantity and frequency did not change the finding. The relationship between GGT and BMI was estimated after splitting the sample into normal (BMI ≤ 25 kg/m²), and overweight (BMI > 25 kg/m²), subjects. The correlation between GGT and BMI in normal weight men at T1 was r = 0.15, p = 0.09, at T2 r = 0.00, p = 0.96, and at T3 r = 0.09, p = 0.09. In overweight subjects, correlation at T1 was r = 0.40, p = 0.20, at T2 r = 0.36, p < 0.05, and at T3 r = 0.44, p < 0.001. Controlling for the effect of alcohol consumption and/or age did not alter these conclusions. Testing for the interaction of age, BMI, and alcohol consumption did not yield relevant results. We concluded that GGT is positively related to age in the 20s to late 30s and to BMI in overweight subjects; both relationships of age and BMI were independent of alcohol consumption. The interpretation of GGT should take age and BMI into account when suspecting subclinical alcohol problems in young men.     

The Social Context of Drinking among High School Drinking Drivers

Abstract

Over 2,000 high school students were surveyed with an anonymous questionnnaire to determine their frequency of drunk driving, social context of alcohol consumption, beliefs about drunk driving, and quantity and frequency of alcohol consumed. About 10% of the sample was identified as drunk drivers and they were compared with non-drunk driving drinkers according to a number of measures of where and why they drank. The results revealed highly significant differences in the social context of alcohol consumption for beer, wine, and liquor consumption. Across all three beverage categories, the most important discriminating social context factors were drinking at a dormitory and drinking to get along better on dates. Beer and liquor consumption were more important than wine consumption for discriminating drunk drivers from the non-problem drinking high school population. Quantity and frequency measures of alcohol consumption along with belief measures about drinking and driving did not substantially increase the discrimination between the two groups, but significantly increased the predictive power in a multiple regression analysis including the social context of alcohol consumption items.     

Effects of Acute and Varying Amounts of Alcohol Consumption on Alkaline Phosphatase, Aspartate Transaminase, and γ-Glutamyltransferase

Acute alcohol consumption has no effect on the levels of enzymes in serum. Regardless of the amount consumed, no significant changes in serum enzymes were observed. Age-related differences in gamma-glutamyltransferase were not apparent. Peak blood alcohol concentration and consumption are not related to the body mass. Screening of drunk drivers for detecting problem drinkers could be undertaken by performing biochemical measurements of serum enzymes, especially gamma-glutamyltransferase.     

Serum β-Hexosaminidase as a Marker of Heavy Drinking

β-hexosaminidase, also called n -acetyl-β- d -glucosaminidase, is a lysosomal glycosidase, which has been found to be increased in the sera of alcoholics admitted to acute detoxification treatment. To study serum β-hexosaminidase (β-HEX) as a marker of heavy drinking, it was compared with GGT, ASAT, and ALAT in three study groups: twentyfive drunken arrestees, 16 social drinkers, and 27 teetotallers. Mean serum β-HEX levels were two times higher among drunken arrestees than among social drinkers or teetotallers. Average daily alcohol intake during the preceding 30 days in the pooled group of drunken arrestees and social drinkers correlated positively ( r = 0.69; p < 0.0001) with serum β-HEX. The sensitivity of β-HEX in the detection of heavy drinking, defined as over 60 g ethanol daily, was 85.7% compared to 47.6% for GGT. The specificity of β-HEX was 97.6%. The positive correlations between β-HEX and ASAT ( r = 0.74; p < 0.0001) and ALAT ( r = 0.41; p < 0.05) indicate that increased serum β-HEX level may reflect early liver injury. Serum β-HEX seems to be a sensitive biological marker of heavy drinking reflecting better the ingested amounts of alcohol than GGT.     

Comparing the Diagnostic Accuracy of Carbohydrate-Deficient Transferrin, γ-Glutamyltransferase, and Mean Cell Volume in a General Practice Population

In certain populations, the biological alcohol marker carbohydrate-deficient transferrin (CDT) is known to have a high diagnostic accuracy. The aim of this study was to compare the diagnostic accuracy of CDT, gamma-glutamyltransferase (gamma-GT), and mean cell volume (MCV) in a general practice population; more specifically, to ascertain whether CDT is a better tool than gamma-GT and MCV for (early) recognition of excessive alcohol use. To represent the general practice situation as realistically as possible, three different drinking patterns are defined: irregular excessive, regular excessive, and very excessive. From a sample of 524 men from seven general practices, sensitivity, specificity, and predictive values of the three markers for the three drinking patterns were compared, and receiver-operating characteristic analysis was used to compare differences between the markers. The results indicate that drinking patterns do influence the (difference in) diagnostic accuracy. CDT has a higher diagnostic accuracy for all three drinking patterns than gamma-GT and higher predictive values for hazardous [(ir)regular excessive] drinking patterns than MCV. However, receiver-operating characteristic analyses failed to demonstrate a significant difference between these patterns. It is concluded that the performance of all tests is too low to be useful for screening procedures in a general population; however, some tests may be useful for case finding. CDT seems to be the best alcohol marker available, although the difference between CDT and MCV is small.     

Loss of Control Drinking among First Offender Drunk Drivers

A mathematical model of alcohol consumption, which characterizes individual drinking in terms of frequency of consumption and subsequent loss of control drinking once consumption has been initiated, is introduced. The model provides a conceptual link between behavioral indices of alcohol consumption patterns and theoretical models of the role of loss of control drinking in the genesis of alcohol dependence and alcoholism. Based on data from a large sample of first offender drunk drivers, it is shown that specific measures of consumption patterns can be used to provide individual estimates of parameters of the model. These estimates are shown to be strongly related to one measure of alcohol dependence and to introspective reports of loss of control drinking.     

Immunohistochemical Study of T Cell Receptor γδ Cells in Chronic Liver Disease

The distribution and phenotypic characterization of T cell receptor (TCR) gamma delta cells in human liver tissue was investigated immunohistochemically at light and electron microscopic levels. In chronic liver disease, there was a significant increase in the number of TCR gamma delta cells and in the percentage of TCR gamma delta cells to CD3+ cells in the portal areas and hepatic sinusoids. Hepatic TCR gamma delta cells were classified as small or large gamma delta cells. Large gamma delta cells were increased in chronic liver disease, whereas both small and large gamma delta cells were increased in the portal areas and hepatic sinusoids in liver cirrhosis. The increased TCR gamma delta cells were of the BB3+ (peripheral) type, indicating that TCR gamma delta cells in the liver were of the same lineage as those in the peripheral blood. In addition, the majority of the TCR gamma delta cells in the portal areas of liver cirrhosis patients were CD4- and CD8- (double negative). Immunoelectron microscopy showed that the large gamma delta cells were lymphoblastoid and contained multivesicles. The present study clearly demonstrated that there are two types of TCR gamma delta cells, and that these cells were significantly increased in the livers of patients with chronic liver disease. This suggests that they may be involved in regulation of the immune response and hepatocellular damage in chronic liver disease.     

Diagnostic Value of Serum γ-Glutamyl Transferase Isoenzyme for Hepatocellular Carcinoma: A 10-Year Study

Serum gamma-glutamyl transferase (GGT) was separated into nine to 11 isoenzyme bands (designated as GGT I-XI) by vertical slab electrophoresis on polyacrylamide gradient gel. The diagnostic value of GGT isoenzyme II (GGT II) for hepatocellular carcinoma (HCC) was studied, and the results were as follows: 1) GGT II was positive in 90% of 90 cases of HCC, and negative in most patients with acute and chronic viral hepatitis, extrahepatic tumors, in pregnant women, and in healthy controls; 2) the positive rate of GGT II assay was higher than that of alkaline phosphatase isoenzyme I (ALP I), alpha-fetoprotein (AFP), and alpha 1-antitrypsin (AAT) in 101 cases of HCC. In cases in which the AFP was greater than 50 ng/ml or less than 50 ng/ml, the positive rates of GGT II were 70.8% and 75-100%, respectively; 3) of 14 cases of small-size HCC, the positive rate of GGT II was 78.6%, which was higher than that of AFP (50%), AAT (28.6%), and ALP I (0%); 4) of 62 cases that were false-positive for GGT II assay, 24.2% developed into HCC during a follow-up of 2.1-20 months. In subjects with persistent and recurrent positivity of GGT II, 86.7% and 22.2%, respectively, developed HCC. No patient with temporal positivity of GGT II developed HCC. The results show that GGT II can be applied as an additional marker for HCC, and is valuable not only for the diagnosis of clinical HCC, but for the detection of small or subclinical HCC. Periodic follow-up with assay of GGT II in patients at high risk for HCC may predict the development of hepatoma.     

A Comparison of the Homozygous States for Gγ and GγAγδβ Thalassaemia

One Arabic and two Indian patients with thalassaemia intermedia produce only Hb F for the G gamma type. Haemoglobin synthesis studies and genetic analysis indicate that they are homozygous for G gamma delta beta thalassaemia. The findings in these patients and their heterozygous relatives are compared with those in an individual homozygous for G gamma A gamma delta beta thalassaemia. From this analysis, and from previously reported data on G gamma A gamma delta beta thalassaemia, the phenotypic expression of the two varieties of delta beta thalassaemia is defined. The relationship between the clinical expression and molecular pathology of these forms of delta beta thalassaemia is discussed.     

Alcohol-induced Enhancement of Intestinal γ-Glutamyl Transpeptidase Activity in Rats and Humans: A Possible Role in Increased Serum γ-Glutamyl Transpeptidase Activity in Alcoholics

It is a well-known phenomenon that serum gamma-glutamyltranspeptidase (gamma-GTP, EC 2.3.2.2.) activity is increased after chronic consumption of ethanol, and gamma-GTP has been, therefore, widely used as a sensitive marker for detection of alcoholism and its related liver disease. However, the precise mechanisms whereby the chronic ethanol consumption leads to an increase in serum gamma-GTP activity are not fully understood. In the present study, we investigated the relationship between the intestinal and serum gamma-GTP activities after chronic ethanol consumption both in rats and humans. Chronic ethanol feeding to rats resulted in a significant increase in serum gamma-GTP activity associated with a significant increment of the intestinal gamma-GTP activity. The histochemical staining of gamma-GTP in the mucosa of the small intestine of these animals demonstrated enhanced gamma-GTP activity at the microvilli of the brush border membrane, lamina propria of the mucosa, and endoplasmic reticulum of the intestinal epithelial cell. The augmented activity in the lamina propria was mainly localized at the submucosal lymphatics. Histology of the small intestine of human alcoholics was, more or less, similar to those observed in alcoholic rats. We further investigated the gamma-GTP activity in the mesenteric lymph using the animal model of lymphorrhea, and found that the gamma-GTP activity was increased by 83% when expressed per unit of lymph in the ethanol-fed rat, accompanied by a marked decrease of serum gamma-GTP activity, suggesting a close relationship between the serum and the intestinal gamma-GTP via the lymphatic channel.(ABSTRACT TRUNCATED AT 250 WORDS)     

Alcohol Use and Abuse: Heavy Drinking among Methadone Clients

This paper discusses alcohol use among methadone maintenance clients and narcotics users not in treatment. The data are derived from the Tri-State Ethnographic Project, a study of four methadone maintenance clinics in three states. Data indicate that methadone clients consume more alcohol than comparable age groups in the general population, but not more alcohol than narcotics users not in treatment. For a portion of the treatment population, however, heavy drinking presents significant problems. Sixteen percent of the treatment sample were found to be abusive pattern drinkers; that is, persons who report not only drinking heavily but also spending a great deal of time hanging out on the street, getting high, and consuming many other additional drugs. These abusive pattern drinkers reflect a pattern of polydrug use which began in their early teens and report multiple unsuccessful treatment attempts.     

GγAγ(δβ)°-thalassaemia and a new form of γ globin gene triplication identified in the Yugoslavian population

Among several hundred apparently healthy Yugoslavian adults with slightly elevated levels of fetal haemoglobin, we have identified two distinct abnormalities. (a) A G gamma A gamma(delta beta)0-thalassaemia heterozygosity with an approximately 15 kb deletion which involves part of the delta globin gene and the beta globin gene. This deletion is probably the same as that seen among Italians (Ottolenghi et al, 1982; Carè et al, 1984). (b) A nondeletion form of hereditary persistence of Hb F which is caused by a gamma globin gene triplication of the (+)G gamma.(+)G gamma.A gamma type. It is characterized by the presence of some 5% Hb F in the heterozygote containing nearly 100% G gamma chains. The C----T mutation at position--158 5' to the G gamma chain [(+)G gamma], identified through analyses of Xmn I digests, was present at both G gamma globin genes. This mutation is known to be associated with increased G gamma chain production (Gilman & Huisman, 1985), and thus is responsible for the increased G gamma chain production in these heterozygotes. The condition is different from the (+)G gamma.(+)G gamma nondeletion type of HPFH which has been observed in heterozygotes of two Black families, and is associated with the presence of 3-4% Hb F (with mainly G gamma chains) in heterozygotes.     

Relationship between γ-Glutamyl Transpeptidase and Mean Urinary Alcohol Levels in Alcoholics While Drinking and after Alcohol Withdrawal

In 42 patients with alcoholic liver disease in whom daily urinary ethanol concentrations were measured for 3 months, after an abstinence of at least 1 month, serum gamma-glutamyl transpeptidase (GGT) activity was found to correlate (r = 0.69; p less than 0.0001) with mean urinary alcohol levels. The half-life of serum GGT decay in 32 patients who remained abstinent for an 8-week period was calculated to be 26 days. This prolonged half-life can result in high serum GGT levels in patients abstinent for prolonged periods, in whom serum GGT baselines before abstinence were very high. Individual variations in serum GGT levels should be interpreted in relation to continued alcohol consumption, keeping in mind the long half-life for this enzyme in these patients.