The ALT upper reference interval debate: Blame it on the alcohol

Abstract

BackgroundIn 2017, the American College of Gastroenterology (ACG) and the North American Society of Pediatric Gastroenterology, Hepatology and Nutrition published clinical guidelines recommending the use of alanine aminotransferase (ALT) upper reference limits (URL) of 33, 25, 26, and 22 U/l for men, women, boys, and girls, respectively. This was opposed by laboratory experts who advocated for the use of higher URL of 59, 41, 33, and 24 U/l instead. We suspected that the variable inclusion of individuals who consumed alcohol to be a major contributing source of URL variability and debate. MethodsOutpatient ALT data (n = 7379) were collected from unique individuals ≥13 y with BMIs of ≥19 and ≤25. A total of 222 (3%) were excluded due to suspected liver disease. Patients were split into a pediatric group (age 13–17 y), an alcohol-restricted adult group (age 18–20 y), and adults with access to alcohol by decade (i.e., age 21–29, 30–39, 40–49, 50–59, 60–69, 70–79, and ≥ 80 y). All ALT values were measured on Roche Cobas 8000 with pyridoxal phosphate and traceable to the IFCC-reference measurement procedure. ResultsWe derived URL similar to CALIPER for our pediatric population, but closer to ACG-proposed URL in our alcohol-restricted adult group. The URL increased significantly in men and women for all other age groups. ConclusionsThe discrepancy in ALT URL in clinical laboratories may be attributable in part due to the variable inclusion of individuals who recently consumed alcohol in local population derivation studies.