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

BACKGROUND: 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.

METHODS: 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).

RESULTS: 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.

CONCLUSIONS: 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.