Association between alanine aminotransferase within the normal range and all-cause and cause-specific mortality: A nationwide cohort study

Background and aim We sought to determine the association between alanine aminotransferase (ALT) in the normal range and mortality in the absence of liver dysfunction to better understand ALT's clinical significance beyond liver injury and inflammation. Methods A cohort of 2,708 male and 3,461 female adults aged 20-75 years without liver dysfunction (ALT<30 in males & <19 in females, negative viral serologies, negative ultrasound-based steatosis, no excess alcohol consumption) from the National Health and Nutrition Examination Survey (NHANES)-III (1988-1994) were linked to the National Death Index through December 31, 2015. Serum ALT levels were categorized into sex-specific quartiles (Females: <9, 9-11, 11-14, >= 14 IU/L, Male: <12, 12-15, 15-20, >= 20 U/L). The primary outcome was all-cause mortality. Hazard ratios (HRs) were estimated, adjusting for covariates and accounting for the complex survey design. Results Relative to males in the lowest quartile (Q1), males in the highest quartile (Q4) had 44% decreased risk of all-cause mortality (aHR [95% CI]: 0.56 [0.42, 0.74]). Females in Q4 had 45% decreased risk of all-cause mortality (aHR [95% CI]: 0.55 [0.40, 0.77]). Males with BMI <25 kg/m(2) in Q4 had significantly lower risk of all-cause mortality than Q1; however, this association did not exist in males with BMI >= 25 (BMI<25: 0.36 [0.20, 0.64], BMI >= 25: 0.77 [0.49, 1.22]). Risk of all-cause mortality was lower in males >= 50 years than in males<50 (age >= 50: 0.55 [0.39, 0.77], age<50: 0.81 [0.39, 1.69]). These age- and BMI-related differences were not seen in females. Conclusion ALT within the normal range was inversely associated with all-cause mortality in U.S. adults.