Age Dependence of Liver Enzymes: An Analysis of Over 1,300,000 Consecutive Blood Samples

Upper levels of normal for alanine aminotransferase (ALT), aspartate aminotransferase (AST), and γ-glutamyltransferase (GGT) generally take sex into account, but not age. This simplification may lead to misclassification and burden the patient and health system unnecessarily.

Consecutive blood samples were analyzed from a German laboratory. Subcohorts included samples from a prescribed routine check-up and a healthy cohort, defined as patients without increased GGT, triglyceride, cholesterol, glycated hemoglobin, or glucose levels, and without known hepatitis B.

A total of 1,369,180 blood samples were analyzed from 601,779 participants (50.8% female; mean age, 58.5 y; SD, 18.0 y). There is an extreme age dependence in ALT values for men: increased values were seen in 20.0% (95% CI, 19.5%-20.4%) of patients in the age group of 25 to 34 years, but only 6.7% (95% CI, 6.4%-7.0%) for the ages of 65 to 74 years. The 95th percentile reaches values greater than 80 U/L instead of 50 U/L at the age of 35, and decrease to less than 50 U/L by the age of 75. Similar qualitative results were found in the healthy and prescribed routine check-up subcohorts. The age dependence is much weaker for ALT in women. The proportion of women with an increased AST level increases from approximately 6% to 12% at approximately age 50. The 95th percentile for GGT increases up to the age of 60 in men, and throughout life in women.

Current guidelines and reference values for ALT imply that subsequent diagnostics are needed for a large proportion of young men. Our data strongly suggest that age adaptation should be considered.