a Department of Preventive Medicine, College of Medicine, Kosin University, 34 Amnam-Dong, Suh-Gu, Pusan, Korea, 602702. E-mail: ducky{at}ns.kosinmed.or.kr
b Health Care Center, Pohang Steel Company, Pohang, Korea.
c Department of Environmental Health, Harvard School of Public Health, Boston, MA, USA
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Abstract |
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Methods This study population consisted of 6846 male workers in a steel manufacturing company who had undergone health examinations in 1994 and 1998.
Results The risk for elevated both aspartate aminotransferase (AST) and alanine aminotransferase (ALT) values over the four years increased with the baseline BMI and BMI changes, but not with alcohol consumption. Compared with the subject BMI <20, the adjusted odds ratios (OR) for those with baseline BMI 2021.9, 2224.9, 25 were 1.2, 1.6, 1.7 in AST and 1.4, 2.4, 2.8 in ALT, respectively. Compared with subjects who either lost or maintained their weight, the adjusted OR for men with slight, moderate, and heavy weight gain were 1.7, 2.6, 6.8 in AST and 2.4, 3.9, 11.3 in ALT, respectively. However gamma-glutamyl transferase (GGT) was associated with BMI changes and baseline alcohol consumption, not with baseline BMI and changes in alcohol consumption. Compared with subjects who lost or maintained weight, the adjusted OR for men with slight, moderate, and heavy weight gain were 2.4, 4.4 and 8.5, respectively. In comparison with non-drinkers, the adjusted OR for light, moderate and heavy drinkers were 1.8, 2.1 and 5.8, respectively.
Conclusion These data suggest that body weight, rather than alcohol consumption, may be the major factor in determining the serum level of liver enzymes. Even when body weight was not generally considered to be overweight, slight to moderate gains in weight were associated with increases in serum liver enzymes.
Keywords Liver enzymes, body weight, alcohol consumption, aspartate aminotransferase, alanine aminotransferase, gamma-glutamyl transferase
Accepted 10 April 2001
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Introduction |
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Obesity has also been identified as an important factor known to contribute to raised levels of serum liver enzyme in several cross-sectional studies.58 In the Dionysos study,9 it appeared that obesity rather than alcohol abuse was the main cause of raised values of ALT and the presence of fatty liver.
There have been a few studies evaluating the effects of the changes of alcohol consumption or the changes of body mass index (BMI) on the level of liver enzymes in a prospectively systematic way among apparently healthy people.1013 In these studies, the effect of the changes of alcohol consumption was very weak on liver enzyme, in comparison to that of the BMI change. This is an apparently surprising result given the strong association between alcohol consumption and serum liver enzymes consistently reported in many cross-sectional studies from western countries.1,2 Some clinical-based studies1416 have also showed that the effect of weight loss seemed to be more crucial in normalizing the liver enzyme than reduced alcohol consumption.
However, one study which analysed liver enzymes separately showed that the effect of body weight or alcohol consumption could be different depending upon which liver enzyme is assessed.10 In addition, most studies1013 published to date have usually focused on moderate or severe obesity, defined as a BMI >25. The aim of this prospective study was to investigate the association of baseline BMI, BMI changes, baseline alcohol consumption, and changes in alcohol consumption on serum liver enzyme activity in male workers, most of whom were in a normal range of BMI at baseline, at a large steel company in the Republic of Korea.
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Methods |
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Measurement
Information on lifestyle factors including cigarette smoking, alcohol consumption, exercise, and medical history were obtained by self-reported questionnaires. Each year, all workers were asked to complete the same, or slightly modified, questionnaire. For each questionnaire, changes spotted by a computerized data system (which contained information from previous years) were confirmed by a nurse in a direct interview.
The workers were asked how many times per week or per month they consumed alcohol and the typical quantities consumed. They were asked to estimate the amount in terms of soju, a popular Korean liquor. Based on this information the amount of alcohol consumed per week was calculated. All subjects were divided into four groups by the baseline amount of alcohol consumption (non-drinker; light drinker, 1180 g/week; moderate drinker, 181360 g/week; heavy drinker, 361+ g/week). The population was stratified into four groups by changes in alcohol consumption (decreased, no change, increased 190 g/week, increased 91+ g/week). The BMI value, defined as weight (kg)/height (m2), was used as a weight index; and during weighing, almost all subjects wore the standard company uniform. Subjects were classified into four groups according to baseline BMI or BMI change, respectively. The criteria for the former were: <20 kg/m2; 2021.9 kg/m2; 2224.9 kg/m2; and 25 kg/m2. Criteria for the latter were: weight loser or maintainer,
0 kg/m2 or 0 kg/m2; slight weight gainer, 0.11.0 kg/m2; moderate weight gainer, 1.12.0 kg/m2; heavy weight gainer, >2.0 kg/m2.
Venous blood samples were obtained from a cubital vein after overnight 12 hours fasting. The serum samples were kept at 4°C and analysed within 48 hours. Laboratory tests were performed with an automatic analyser (Hitachi 7170, Japan) by optimized methods based on the recommendations of the Korean Society for Clinical Chemistry, at 37°C. Our normal ranges (U/L) for men were as follows: AST 33; ALT
35; GGT
50.
Statistical analyses
The relationship between alcohol consumption and BMI, and the prevalence and incidence of elevated liver enzyme were analysed by multiple logistic regression, using the SAS statistical program, version 6.12. In the incidence analyses, we included four main variables (baseline BMI, baseline alcohol consumption, BMI change, change in alcohol consumption), covariates (age, cigarette smoking [pack-years], exercise [frequency/week], baseline AST or ALT or GGT [baseline for the dependent variable]), and interaction terms between main factors. There were no interaction terms that reached statistical significance; therefore, these terms were dropped from the final model. We included baseline AST or ALT or GGT as covariates because amounts of changes of these enzymes during 4 years were dependent upon the baseline value of these enzymes. Those with relatively high values of serum liver enzymes at baseline, although in normal range, tended to increase more than those with low values. In the prevalence analyses, two main variables (baseline BMI, baseline alcohol consumption) and covariates (age, cigarette smoking [pack-years], exercise [frequency/week]) were included in the final model. The P-values used are two-sided, and values <0.05 were regarded as statistically significant.
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Results |
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Discussion |
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Several cross-sectional and clinical studies58 have shown consistently that the increased serum activity of various liver enzymes is related to overweight or obesity. The results of a few prospective studies10,12,1416 also confirmed this association. However, earlier studies usually focused on moderate or severe obesity with BMI >25. In this prospective study, higher levels of adiposity as assessed by baseline BMI and BMI change were monotonically related to an increase in the incidence of elevated serum liver enzymes, especially AST and ALT, even though most of our subjects had a BMI within the normal range. Our study allows a more precise quantification of the dose-response relationship than has been possible previously due to the large sample size. Also, we explored the association of baseline BMI and BMI change simultaneously and showed that the effect of BMI change was a more important factor in developing abnormal liver enzymes than was baseline BMI. To our knowledge, this is the first study to report these findings. Among our subjects, those with higher baseline BMI tended to experience an increase in body weight less than those with lower baseline BMI. Hence, one of these factors should be considered as a confounder when interpreting associations with the other. Although Bruns et al.10 assessed the effect of body weight change, they did not consider these two covariates concurrently as possible confounders.
Among liver enzymes, the serum activities of ALT were more clearly related to BMI than were the other enzymes. These findings were similar to those observed in other studies.7,9,10 On the basis of such observations, Wejstal et al.17 suggested that ALT values should be corrected for body weight, especially when ALT measurements are used as a surrogate test in screening for non-A, non-B hepatitis. According to another study,18 AST values also should be corrected for body weight because in various animal species, ranging from mice to cattle, the expected enzymatic activity can be expressed as a function of a power of the weight.
AST and ALT had a surprisingly weak or non-existent relationship with alcohol consumption in both the cross-sectional and longitudinal analyses in our study; although the relationship between alcohol consumption and GGT was clear, as expected. The studies9,10,19 from western countries reported that the magnitude of the effect of alcohol consumption was similar to, or slightly smaller than, that of obesity. This could be because the total alcohol consumption in our subjects might have been lower than in other studies. Alternatively, Asians may be less sensitive to alcohol than Caucasians. Studies3,4 from Japan also reported that alcohol consumption was not significantly related to ALT or AST.
The Serum GGT level showed a strong relationship only with BMI change, but not baseline BMI. The importance of BMI change means that the effects of adiposity might be temporary. A 7-year longitudinal population study from Norway also showed that the change in BMI was the single strongest determinant of change in GGT.12 Our study suggested that liver enzymes could be influenced by a slight weight change even within normal range.
One of the most interesting findings of this study was that GGT showed a relationship only with baseline alcohol consumption, not change in alcohol consumption, the opposite finding to the relationship observed for BMI. As far as we know, though, there has been no previous study exploring the relationships between both baseline and the changes of alcohol consumption, and liver enzyme concurrently, the results of some studies support our finding. As a screening test for alcoholism and alcohol abuse, the sensitivity of GGT has been considered to be acceptable, but its specificity is poor.20 In contrast to this, GGT has been found to have reasonable specificity but low sensitivity to changes in alcohol consumption.21 The Tromsø study12 in Norway also reported a strong relationship between alcohol consumption and GGT in a cross-sectional setting, but a surprisingly weak association between the changes of alcohol consumption and the changes of GGT in longitudinal analyses. They interpreted this as reflecting the imprecision of their alcohol questions, which may have introduced random measurement errors that obscured the true changes in alcohol consumption. However, our result suggested that it could be a real association. Some investigators22,23 have suggested that elevated GGT activity in drinkers is probably related more closely to the biological effects of alcohol than to the amount of alcohol consumption.
In conclusion, these data indicate that body weight rather than alcohol consumption may be the major factor in determining the level of liver enzyme, though some ethnic differences may need to be taken into consideration. In particular, even slight or moderate gains in weight, and levels of body weight not generally considered to be overweight, were associated with increases of liver enzyme. With regard to the alcohol consumption, further study is needed to clarify the reason for the small effect of changes in alcohol consumption on GGT.
KEY MESSAGES
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References |
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