γ-Glutamyl Transferase Is Associated with Mortality Outcomes Independently of Fatty Liver

High serum enzyme activity levels of γ-glutamyl transferase (GGT) are associated with increased risk of mortality, but whether this is mediated by fatty liver, as a common cause of high GGT levels, is uncertain. Our aim was to test whether GGT levels are associated with all-cause, cancer, and cardiovascular (CVD) mortality, independently of fatty liver.

In an occupational cohort (n = 278 419), causes of death (International Statistical Classification of Diseases and Related Health Problems, 10th revision) were recorded over 7 years. Liver function tests and liver fat [measured by ultrasonographic standard criteria or fatty liver index (FLI)] were assessed at baseline. We used Cox proportional hazards models to estimate adjusted hazard ratios (HRs) and 95% CIs of all-cause, cancer, and CVD mortality for GGT quartiles (with lowest GGT quartile as reference).

There were 136, 167, 265, and 342 deaths across increasing GGT quartiles. After adjusting for liver fat (by ultrasound diagnosis) in the fully adjusted model, all-cause and cancer mortality were increased in the highest GGT quartile [HR 1.50 (95% CI 1.15-1.96) and 1.57 (1.05-2.35), respectively]. For CVD mortality, the hazard was attenuated: HR 1.35 (95% CI 0.72-2.56). After adjusting for FLI in the fully adjusted model, HRs for all-cause, cancer, and CVD mortality were 1.46 (0.72-2.56), 2.03 (1.02-4.03), and 1.16 (0.41,3.24), respectively.

There were similar hazards for all-cause and cancer mortality and attenuated hazards for CVD mortality for people in the highest GGT quartile, adjusting for fatty liver assessed by either ultrasound or FLI.