| Abstrakt: |
Alcohol dependence and long‐term excessive alcohol use may cause liver damage, but only some patients develop cirrhosis. Similarly, high alcohol intake without evident liver disease often but not always produces abnormal enzymatic liver function tests (LFTs), particularly gamma‐glutamyl transferase (GGT). We postulate that the factors predisposing to cirrhosis in alcoholics and to liver enzyme abnormality in drinkers are similar, and that biochemical LFTs could therefore be useful as markers of risk of alcoholic liver disease in excessive drinkers. Data from participants in twin and twin‐family studies on alcohol use and dependence were used to identify 1,003 people who had reported excessive alcohol intake (28 drinks or more per week). A total of 962 of these provided blood for biochemical tests at the same time. Body mass index (BMI) and biomarkers of metabolic syndrome, inflammation, and iron stores were used in logistic regression with abnormality in serum GGT, alanine aminotransferase (ALT), or aspartate aminotransferase (AST) as outcomes. We conducted genome‐wide association analyses for GGT,ALT, and ASTseparately in the group reporting excessive alcohol intake (N= 951) and a low‐intake group reporting 14 drinks or fewer per week (N= 8,716), and compared results. Abnormal GGTand ALTamong excessive drinkers were associated with higher BMI, triglycerides, insulin, uric acid, C‐reactive protein, ferritin, and transferrin saturation; and with lower high‐density‐lipoprotein cholesterol. Abnormal ASTwas associated with triglycerides, ferritin, and transferrin saturation. ALTwas significantly associated with variants at reported genetic loci for alcoholic liver disease (PNPLA3, rs738409, p= 0.0076; TM6SF2, rs10401969, p= 0.0076; HSD17B13, rs10433879, p= 0.0024). Known risk factors for alcoholic cirrhosis including obesity and markers of metabolic syndrome, iron overload and inflammation are associated with liver enzyme abnormality in excessive drinkers. Several common liver function tests (GGT, ALT, AST) are abnormal in many, but not all, high‐risk drinkers. We tested potential causes for variation in this response to chronic alcohol use, including obesity, lipids and iron overload, finding significant overlap with known risk factors for alcoholic liver disease. Genetic variants which increase risk for alcoholic cirrhosis increased ALT, but not GGT or AST, in the high‐risk drinkers. Abnormal enzyme results in high‐risk drinkers may help to identify those most susceptible to cirrhosis. |
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