Abstract
OBJECTIVE: Fatty liver disease (FLD) has been associated with extrahepatic morbidity outcomes. However, reports on the association of FLD, assessed using fatty liver index (FLI), with mortality outcomes have been inconsistent. Our objective was to examine the effect of metabolic factors (blood pressure, insulin, fasting glucose, lipoproteins) on the associations of FLI with mortality outcomes among middle-aged men. STUDY DESIGN: Prospective cohort study. METHODS: Our subjects were 1893 men at baseline from 1984 to 1989 in the Kuopio Ischaemic Heart Disease Risk Factor Study cohort. Multivariable Cox regression models were used to analyse the association of baseline FLI, with the HRs for all-cause, disease, cardiovascular, non-cardiovascular and cancer mortality outcomes. RESULTS: The mean FLI in the FLI categories were 16.2 in the low and reference category (FLI<30), 43.4 in the intermediate FLI category (FLI=30-<60) and 77.5 in the high FLI (FLD) category (FLI≥60). Over an average follow-up of 20 years, 848 disease deaths were recorded through Finnish national cause of death register. In models adjusted for constitutional, lifestyle and inflammatory factors, for the high (FLI≥60) vs low (FLI<30) FLI category, the HRs (95% CI) for mortality outcomes were 1.50 (1.26-1.78) for all-cause mortality; 1.56 (1.31-2.86) for disease mortality; 1.51 (1.18-1.94) for cardiovascular disease (CVD) mortality; 1.42 (1.12-1.80) for non-CVD mortality and 1.45 (1.02-2.07) for cancer mortality. With further adjustment for metabolic factors, the HRs were 1.25 (1.01-1.53) for all-cause mortality; 1.26 (1.02-1.56) for disease mortality; 1.06 (0.78-1.43) for CVD mortality; 1.46 (1.09-1.94) for non-CVD mortality and 1.49 (0.97-2.29) for cancer mortality. CONCLUSION: High FLI (FLD) is associated with increased risks of mortality outcomes. The FLI-CVD mortality association can be largely explained by metabolic factors. Persons with FLD should be monitored for metabolic deterioration and extrahepatic morbidity to improve their prognoses.