The change in terminology from nonalcoholic fatty liver disease (NAFLD) to metabolic dysfunction-associated fatty liver disease (MAFLD) has raised heated discussion. Our study aims to investigate which has closer association with all-cause and cause-specific mortality in a population-based cohort. We investigated the association between fatty liver disease and mortality in 12,480 adults from National Health and Nutrition Examination Survey III with a medium follow-up time of 22.7 years. Characteristics were compared in participants without NAFLD or MAFLD, with only NAFLD, only MAFLD, or both; survival analysis and subgroup analysis were applied. Participants with NAFLD or MAFLD were highly overlapped (Weighted Cohen’s kappa coefficient 0.78). MAFLD increased the risk for total mortality in a greater magnitude than NAFLD (HR: 2.07 [95% CI 1.86, 2.29] vs. 1.48 [1.35, 1.65]) in crude, but the risks were neglectable when metabolic parameters were adjusted. The risk for cardiovascular, neoplasm and diabetes-related mortality was similar between MAFLD and NAFLD. In reference to participants without NAFLD or MAFLD, patients with only NAFLD showed a reduced risk for total (0.48 [0.34, 0.68]) and neoplasm mortality (0.46 [0.24, 0.89]), while participants with only MAFLD was independently associated with enhanced risk for total (1.74 [1.40, 2.15]), neoplasm (1.94 [1.30, 2.90]) and diabetes-related mortality (3.24 [1.05, 9.97]) after adjustment. The risk of MAFLD for overall mortality was consistence between subgroups except for race-ethnicity.

In conclusion, participants with MAFLD or NAFLD were highly concordant. Compared with NAFLD, MAFLD was certified with greater risk in all-cause mortality and similar risk in cause-specific mortality. The new terminology excluded participants with lower mortality risk and included participants with higher risk. Drug development for MAFLD should consider ethnicity difference.


Q. Huang: None. X. Zou: None. X. Zhou: None. L. Ji: None.


National Key Research and Development Program of China (2016YFC1304901, 2016YFC1305603); National Natural Science Foundation of China (81800515); Beijing Nova Program of Science and Technology (Z191100001119026)

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