Alcohol intake, alcohol dehydrogenase genotypes, and liver damage and disease in the Danish general population.
OBJECTIVE
We tested the hypothesis that alcohol, alone and in combination with alcohol dehydrogenase (ADH) 1B and ADH1C genotypes, affects liver damage and disease in the general population.


METHODS
Information on alcohol intake and on liver disease was obtained from 9,080 men and women from the Copenhagen City Heart Study. Biochemical tests for the detection of liver damage were specific for alanine aminotransferase (ALT), aspartate aminotransferase (AST)-to-ALT ratio (AST/ALT), gamma-glutamyl transpeptidase (gamma-GT), albumin, bilirubin, alkaline phosphatase, coagulation factors, and erythrocyte volume.


RESULTS
Increasing alcohol intake was associated with increasing erythrocyte volume, AST/ALT, and levels of ALT, gamma-GT, albumin, bilirubin, coagulation factors, and with decreasing levels of alkaline phosphatase. Multifactorially adjusted hazard ratios for alcoholic liver disease overall were 0.9 (95% confidence interval (CI), 0.6-1.4), 1.4 (0.8-2.5), 1.8 (0.9-3.5), and 4.1 (2.5-7.0) for an alcohol intake of 1-13, 14-20, 21-27, and > or = 28 drinks per week, respectively, compared with drinking <1 drink per week (P for trend<0.0001); the corresponding hazard ratios for alcoholic liver cirrhosis were 1.7 (0.6-4.7), 2.0 (0.8-7.1), 6.5 (2.0-21), and 13 (4.6-37) (P for trend<0.0001). ADH1B and ADH1C genotypes were not associated with and did not modify the effect of alcohol on biochemical tests or risk of liver disease.


CONCLUSIONS
Increasing alcohol intake from none to low (1-6 drinks per week) through to moderate (7-20 drinks per week) and excessive intake (> or = 21 drinks per week) leads to stepwise increases in signs of liver damage with no threshold effect, and to an increased risk of liver disease. The minor changes in biochemical tests for low alcohol intake may not account for subclinical liver disease.
Tolstrup
Janne S
JS
Center for Alcohol Research, National Institute of Public Health, University of Southern Denmark, Copenhagen, Denmark.
Grønbaek
Morten
M
Tybjaerg-Hansen
Anne
A
Nordestgaard
Børge G
BG
D000328:Adult; D000368:Aged; D000426:Alcohol Dehydrogenase / Q000235:genetics*; D000428:Alcohol Drinking / Q000009:adverse effects*; D015415:Biomarkers / Q000097:blood; D003718:Denmark; D005260:Female; D005838:Genotype; D006801:Humans; D008107:Liver Diseases / Q000097:blood / Q000209:etiology* / Q000235:genetics; D008297:Male; D008875:Middle Aged
D015415:Biomarkers; C489332:ADH1B protein, human; C420272:ADH1C protein, human; D000426:Alcohol Dehydrogenase