The association between serum liver enzymes and cancer mortality

Interpreting levels of liver enzymes is often challenging because they may be influenced by metabolic processes beyond the liver. Given their pathophysiologic roles in inflammation and oxidative stress, higher levels of these enzymes may be associated with increased risk of mortality. However, studies have found inconsistent results. Thus, we examined the association of liver enzymes levels with cancer mortality in the general US adult population. We used the US National Health and Nutrition Examination Survey from 1999 to 2016. Kaplan-Meier survival curve comparisons were examined across quartiles of liver enzymes. Cox proportional hazards models were built to examine the relationship between cancer mortality and liver enzymes quartiles without and with adjustment for potential confounding factors. During the 338,882 person-years follow-up, 1059 participants had cancer-related deaths. There was a nonlinear U-shaped relationship between serum alanine and aspartate aminotransferase (ALT and AST) levels and cancer mortality. There was no relationship between cancer mortality and gamma-glutamyltransferase (GGT); however, each 10 IU/L increase in GGT after median was associated with 1% higher mortality risk (HR = 1.01; 95% CI = 1.00, 1.02; P = 0.001). Only subjects with high levels of alkaline phosphatase (ALP) had higher cancer mortality (HR = 1.63; 95CI = 1.30, 2.05; P < 0.001 and HR = 1.52; 95%CI = 1.20, 1.94; P = 0.001, respectively). Only the lowest and highest serum ALT and AST levels are associated with increased cancer mortality. For ALP, the relationship is present at higher levels. The association with GGT was not robust to different analyses. The mechanisms underlying the observed relationships need further exploration.