Associations between serum levels of liver function biomarkers and all-cause and cause-specific mortality: A prospective cohort study

Abstract Background The liver plays critical roles in human health. Circulating level of liver function biomarkers may associate with the long-term and short-term mortality in general population. Methods We used data from US National Health and Nutrition Examination Survey 1988-94 and 1999-2014. People aged ≥ 20 years with measured serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyltransferase (GGT), alkaline phosphatase (ALP), total bilirubin (TB), and albumin (ALB) at baseline were included. All-cause and cause-specific mortality was identified from the National Death Index through 31 December 2015. Additive Cox regression models were applied to assess the correlation patterns between the serum level of these analytes and mortality risk. Results A total of 44,508 participants were included; among them,9,721 deaths occurred during a mean follow-up of 12.5 years. A “J-shaped” correlation was found between serum levels of ALT, AST, and TB and all-cause mortality. The risk of mortality monotonically increased with increasing GGT and ALP levels when their levels exceeded the valley points. A “L-shaped” correlation was found between the serum level of ALB and all-cause mortality. The correlation patterns were comparable among deaths from different causes and were consistent in subgroup and sensitivity analyses. The predictive performance for mortality was superior when all six liver function biomarkers were integrated together (area under ROC curve = 0.706). Conclusion Circulating liver function biomarkers may be informative of survival in general populations and could serve as screening tools to identify individuals at high risk of death.