Serum alanine aminotransferase levels and all-cause mortality

Studies have examined the relationship between serum alanine aminotransferase (ALT) and mortality with inconsistent results. Our aims were to examine the association of normal range serum ALT with mortality, to explore a nonlinear relationship between ALT and mortality, and to investigate whether age modifies this relationship.

We used the continuous National Health and Nutrition Examination Survey (NHANES) from 1999 to 2010. Vital status of the participants was obtained by probabilistic matching between NHANES and the National Death Index. Cox proportional models were used to examine the relationship with and without adjustment for age, sex, race, BMI, hypertension, diabetes, alcohol use, serum triglycerides, prescription drug use, and glomerular filtration rate, and accounting for the sampling methodology of NHANES. Nonlinear relationship was examined using spline (single knot at 17 U/l) regression. Interaction terms were used to examine effect modification by age.

Higher serum ALT was associated with lower all-cause mortality [adjusted hazard ratio (HR)/ALT increment=0.98, 95% confidence interval (CI)=0.97-0.99]; however, this relationship was nonlinear and present only until 17 U/l (adjusted HR/ALT increment=0.93, 95% CI=0.91-0.95) and not thereafter. Age modified the relationship between ALT and mortality; elderly patients (>64 years) had a 6% lower adjusted mortality risk than younger (<35 years) participants (HR/ALT increment=0.94, 95% CI=0.91-0.96; interaction P<0.001).

Increase in serum ALT within the normal range is initially associated with lower mortality, but has no effect after 17 U/l. The elderly show a significantly larger decrease in mortality with an increase in ALT than younger individuals. The mechanisms underlying this relationship need further exploration.