Abstract

Fatty liver is a significant global public health burden, contributing to premature death. To examine whether liver fat scores were associated with increased overall and disease-specific mortality in a United States (US) population-based survey with up to 27years of linked mortality data. We studied 9200 fasted viral hepatitis-negative adults in the third National Health and Nutrition Examination Survey, 1988-1994. Liver fat was predicted using the US fatty liver index (US FLI), fatty liver index (FLI), non-alcoholic fatty liver disease liver fat score (NAFLD LFS), and hepatic steatosis index (HSI). Participants were passively followed up for mortality, identified by death certificate underlying or contributing causes, by linkage to National Death Index records through 2015. Mortality hazard ratios (HR) were calculated using Cox proportional hazards regression to adjust for mortality risk factors. During follow-up (median, 23.3years), cumulative mortality was 31.4% overall and 1.1% with liver disease, including primary liver cancer. Elevated liver disease mortality was associated with a high US FLI (HR, 5.7; 95% confidence interval (CI), 1.3-24.5), and intermediate (HR, 3.1; 95% CI, 1.1-9.1) or high (HR, 11.4; 95% CI, 2.9-44.4) NAFLD LFS, but not with a higher FLI or HSI. Overall and cardiovascular disease mortality was unassociated with higher liver fat scores. In the US population, a higher US FLI and NAFLD LFS were associated with increased liver disease mortality, but not with other mortality outcomes. Liver fat scores may be useful for metabolic health surveillance and long-term liver disease risk stratification and may complement fibrosis markers for tracking.

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