Correlation between serum alanine aminotransferase activity and age: an inverted U curve pattern

Alanine aminotransferase (ALT) activity is the most widely used laboratory test for the recognition of liver disease. Normality limits for values of serum ALT activity have been questioned lately. One reason for this recent uncertainty may be an unrecognized decline in aminotransferase levels in the aging population.

Cross-sectional evaluation of the association between age and ALT activity.

Laboratory data of residents in single home for the aged and of adult subjects in three general practice clinics in Jerusalem, Israel were reviewed, excluding subjects with known liver disease. A single laboratory performed all the tests. We examined the associations of serum aminotransferase levels with age, sex, body-mass-index (BMI), and estimated glomerular filtration rate (GFR). Polynomial regression and analysis of variance (ANOVA) with corrections for multiple comparisons were utilized for the statistical analyses.

One hundred and twenty-eight individuals from the home for the aged and 207 individuals from three family practices were included. ALT activity linearly regressed with age (r = 0.22, p < 0.0001). However, polynomial regression revealed a better fit (r = 0.33, p < 0.0001), creating an inverted U curve with a peak at 40-55 yr. According to age groups, serum ALT level was 19 +/- 13 U/L in those under 40 yr, 25 +/- 19 U/L in 40-55 yr olds, 22 +/- 10 U/L in 56-72 yr olds, 17 +/- 9 U/L in 73-83 yr olds, and 13 +/- 5 U/L in 83-100 yr olds (p < 0.0001). GFR (r = 0.1, p < 0.05) and BMI (r = 0.14, p < 0.01) weakly correlated with ALT. Gender also associated with ALT; 22 +/- 15 U/L in men, and 17 +/- 11 U/L in women (p < 0.005). Multiple regression analysis including age, gender, GFR, and BMI revealed that age (p= 0.01) and gender (p= 0.04) retained association with ALT activity. No such associations were noted for aspartate aminotransferase (AST) activity.

Our data suggest a significant association between age and serum ALT activity. This association is not a simple linear correlation, but rather an inverted-U-like relation. Thus, when interpreting the laboratory results of a subject suspected of liver disease, age should probably be taken into account. Larger-scale studies are needed to better characterize this issue.