Serum Gamma-glutamyltransferase: an epidemiological indicator of alcohol consumption?

British Journal of Addiction (1987) 82, 1027-1031

Serutn Gamma-glutaniyltransferase: an epidemiological indicator of alcohol consumption? H. GJERDE,'* A. AMUNDSEN,^ O.-J. SKOG,^ J. MORLAND' & O. G. AASLAND^ ^National Institute of Forensic Toxicology, P.O. Box 16 Gaustady Oslo 3, Norway, -National Institute of Alcohol Research^ Dannevigsv. 10, Oslo 4, Norway, and ^Directorate for the Prevention of Alcohol and Drug Problems, PO Box 8152 Dep., Oslo /, Norway

Summary' Relations between the alcohol consumption of a population and the prevalence of elevated serum gammaglutamyltransferase (GGT) were studied. Based on empirical data on the prevalance of elevated GGT within different alcohol consumption intervals and the Ledermann theory, relations betzveen mean alcohol consumption of a population and GGT were deduced. Data from other studies were used to verify the relations. The results indicated that the percentage of subjects with elevated GG T in a selected population might be used to gain information about the alcohol consumption of the population.

Introduction Serum gamma-glutamyltransferase (GGT) is one of the most widely used biological markers of heavy drinking.' '' However, some diseases may also lead to an increased serum GGT activity,*' particularly hepatobiliar>' diseases,^ and it has also been reported that some drugs may increase the GGT activity.* The diagnostic value of serum GGT to identify heavy drinking individuals is limited. Among patients studied in general practice, only 50% of those with elevated GGT activities admitted being heavy drinkers.' In the present report we have studied the possibility of using the prevalence of elevated GGT in a population as an indicator of the alcohol consumption of the population. 'Correspondence Io: lUllvatd Gierile, Naiional Instiiuie of Forensic Toxicology, P.O. Box 16 Guustad, N-fl320 Oslo 3, Norway.

Subjects and Methods For the present study, patients attending primary medical care and general hospitals were selected (n = 204). In addition, some abstainers {n^94) and hospitalized alcoholics (n=47) were selected. Alcoholics with a mean alcohol consumption of less than 20 g/day during the last 30 days preceding the day of examination were not included in the study. It has previously been reported that serum GGT is not a good marker of heavy drinking among young subjects,'" therefore, subjects below 30 years of age were not included. The subjects were questioned about their alcohol consumption during the last 30 days using the same standard protocol for all participants. At the same time a blood sample was taken, and the serum GGT activity was measured. Differences m GGT activities have been found between females and males, females had lower mean GGT than men at any alcohol consumption level.'" Therefore, the mean

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GGT was not studied, rather the percentage with elevated GGT, using different limits for the normal ranges for men and women (40 U/1 for women, 50 U/1 for men).

Results and Discussion The relations between alcohol consumption and GGT activity are presented in Fig. 1. The figure shows that the percentage with elevated GGT increased with increasing alcohol consumption. Among the abstainers, only 2% had elevated GGT, while among those drinking more than 40 g/day, more than 50% had elevated GGT activities.

*"

0 0-99 10-39.940-1199 >120 1/V-94H«=163) W-401 (^ = 23) (N-2&\ Alcohol consumption (g.'davl

Figure 1. Relations between alcohol consumption and prevalence of elevated GGT. All subjects were above 29 years of age.

The results presented in Fig. 1 might suggest that serum GGT can be used to gain information about the alcohol consumption in a population. In a population with many subjects drinking more than 40 g alcohol per day, several individuals are expected to have elevated serum GGT. On the other

hard, in a population with only light drinkers and abstainers, few subjects are expected to have elevated GGT. A prerequisite is a low prevalence of non-alcohol related factors increasing the GGT actvity, such as drug use^ and certain diseases.*' According to Ledermann" and Skog'-" there are clo:ie relations between the mean alcohol consumption of a drinking population and the alcohol consumption distribution. Thus, if the mean alcohol consumption is known, the number of subjects at diflerent alcohol consumption levels can be roughly estimated. We chose seven arbitrary mean levels of alcohol consumption ranging from 12.5 to 150 g/day, and the distribution of the alcohol consumption for each level was calculated according to the formula suggested by Ledermann." The results are presented in Table 1. From the data given in Fig. 1 an expected percentage of subjects with elevated GGT could be calculated for each mean consumptior level. These data are also presented in Table 1. The expected relation between GGT and the meiin alcohol consumption (according to Table 1) is pre:iented in Fig. 2. The relationship between mean alcohol consumption and percentage with elevated GGT seemed to be almost linear in the range 0-75 g/day, however, an asymptotic level was probably reacthed around 60%. If other limits of the normal rani;e are used, this asymptotic level will naturally be tlifferent. I h e data presented show that if the mean alcohol coniumption of a population is known, the percentage of subjects with elevated GGT can be estimated. Vice versa. If the GGT activities of the subects in a drinking population are known, the mein alcohol consumption level may be estimated. However, because of the shape of the curve (Fig. 2), the accuracy in the estimation of the alcohol

Table 1. The Distribution of Alcohol Consumption in Groups wi'.h Different Mean Alcohol Consumptions According to Ledermann^\ and the Estimated Proportion of Subjects Expected io Have Elevated GGT within each Group Calculated from Experimental Results Presented in Fig. I Mean alcohol consumption

Proportion (%) of population drinking:

(g/day)

0-9.9 g/day

10-39.9 g/day

2:40 g/day

Expected proportion (%) with elevated GGT

12.5 25 50 75

74.1 44.9 10.6 1.4 0.1 0.0 0.0

19.6 39.1 48.6 32.5 15.2 5.3 1.3

6.4 15.9 40.9 66.1 84.7 94.7 98.7

12.0 17.8 30.2 40.7 48.0 51.9 53.5

100 125 150

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studied, due to a lower sensitivity of serum GGT to heavy drinking among younger subjects.'" "^he use of serum GGT for this purpose may give incorrect estimations of the alcohol consumption when studying groups of subjects where the alcohol consumption distributions deviate a great deal from the Ledermann-distribution. Liver cirrhosis has frequently been used as an ind cator of the prevalence of heavy drinking. 40 80 120 Pecuignot and co-workers found that the risk for Alcohol consumplion Ig/day} cirrhosis grew exponentially with the consumption Figure 2. Relations between the mean alcohol consumplevd,''' and became substantial only when consumptions of populations and the prevalences of elevated GGT. Estimation based on calculations according to Ledermann'' tior exceeded about 80 g/day. In fact, 70% of patents with ascitic cirrhosis drank more than 80 as shown in Table 1 ( ) . Data ftom other studies (presented in Table 2} ( • ) , vertical bars represent standard g/day in Pequignot et a/.'s data. On the other hand, the risk for elevated GGT activity seems to be Ssha;3ed in relation to alcohol consumption (Fig. 1), consumption would be low if more than 50% of the and increases most rapidly in a consumption around subjects in a studied population have elevated GGT. 40 ij/day. Hence, while cirrhosis mortality rates are If the population studied also contains abstainers, paricularly sensitive to changes at fairly high the relation between GGT and alcohol consumption consumption levels, GGT would be most sensitive presented in Fig. 2 is not correct. It could be to changes at moderately high consumption levels. calculated that if a population contained 20% GGT may therefore be a valuable supplement to the abstainers and the alcohol consumption distribution cimosis mortality rates as an index of changes in of the drinkers obeyed the Ledermann formula, the the consumption distribution of a population. mean alcohol consumption would be underesti1 he results presented in this report are primarily mated by 10-15% if GGT was used to estimate the {roil Norwegian subjects. In a recent study of GGT alcohol consumption, if the consumption was less in relation to alcohol consumption in six countries than 75 g/day. (Aasland, O.G. & Amundsen, A., personal comEmpirical data from some previous studies of the munication), it was found that individuals from alcohol consumption in selected populations to- Mexico had higher serum GGT activities in relation gether with GGT data are presented in Table 2. In to :he alcohol consumption than subjects from these studies, the alcohol consumptions were esti- Norway, while drinkers from Kenya had lower mated using different questioning techniques. Some serum GGT in relation to the alcohol consumption. of the alcohol consumption data are based on the The results from Australia and the U.S.A. were reported consumption during 'last week' or 'last more similar to the Norwegian data. The relation year'j others are based on self-reported alcohol betv.'een GGT and alcohol consumption presented consumption 'per week'. Data from three Norwe- in 1 his report can therefore not be applied to gian studies and one Scottish study are presented in popjlations from other countries without caution. the table. In the Norwegian studies, only subjects above 29 years of age were included. In the Scottish study, the ages of the subjects are unknown, however, probably few are below 30 years of age. Acknowledgements The mean alcohol consumptions and the percen- A pan of this study was supported by the World tages with elevated GGT found in these studies are Health Organization (Geneva). This work was also also presented in Fig. 2. As shown in the figure, supported by the Norwegian Ministry of Communithere was a fair agreement between the estimated catitms and Traffic, the Directorate for the Prevention of Alcohol and Dmg Problems, and the relation and the empirical data. Norwegian Abstaining Motorist Association. The results presented indicate that serum GGT may be used to study the alcohol consumption in selected populations, and thus also to monitor changes in the alcohol consumption in a population. References Only subjects above 29 years of age should be 1. SKUDE, G . & WADSTEIN, J. (1977) AmyUse, hepatic _ 60

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