Associations of Serum Liver Enzyme Levels and Their Changes over Time with All-cause and Cause-specific Mortality in the General Population: a Large-scale National Health Screening Cohort Study

Objectives: To investigate the associations of the levels of liver enzymes, such as alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma glutamyltransferase (GGT), at baseline and their changes over time with mortality.

Design: Cohort study.

Setting, Participants And Outcome Measures: We analysed the data of 484 472 individuals from the National Health Insurance Service-National Health Screening Cohort (2002-2013). We used two exposure indices: (1) deciles of baseline ALT, AST and GGT levels measured in 2002 or 2003 and (2) deciles of changes in ALT, AST and GGT levels over a 4 year period (2002-2006 or 2003-2007). We constructed Cox models to evaluate the associations of these exposure indices with mortality (2008-2013).

Results: We found non-monotonic dose-response associations between the baseline levels of ALT and AST and all-cause mortality. We also found a monotonic non-linear association between the baseline levels of GGT and all-cause mortality (10th decile: HR=2.05, 95% CI: 1.93 to 2.18). Compared with the ninth, sixth and fourth deciles of changes in ALT (8-13 U/L), AST (1 U/L) and GGT (-3 to -2 U/L) over time, respectively, the risks of all-cause mortality increased in both the higher and lower deciles of changes in the corresponding liver enzyme levels (10th decile: HR=1.36, 95% CI 1.24 to 1.48; 1st decile: HR=1.46, 95% CI 1.34 to 1.59 for ALT; 10th decile: 1.55, 95% CI 1.40 to 1.71; 1st decile: HR=1.53, 95% CI 1.38 to 1.69 for AST; 10th decile: HR=1.71, 95% CI 1.56 to 1.88; 1st decile: HR=1.67, 95% CI 1.52 to 1.84 for GGT). These non-monotonic dose-response associations remained when analyses were stratified by the medians or quartiles of the baseline liver enzyme levels.

Conclusions: The levels of liver enzymes at baseline and over time showed non-linear associations with mortality.