NAFLD or MAFLD: Which Has Closer Association With All-Cause and Cause-Specific Mortality?-Results From NHANES III

Background: The recent change of terminology from non-alcoholic fatty liver disease (NAFLD) to metabolic dysfunction-associated fatty liver disease (MAFLD) has raised heated discussion. We aim to investigate the association of MAFLD or NAFLD with all-cause and cause-specific mortality to compare the outcomes of the two diagnostic criteria in population-based study. Methods: We recruited 12,480 participants from the Third National Health and Nutrition Examination Survey (NHANES III) with matched mortality data in 2015. Participants were divided into four groups for survival analysis: without NAFLD or MAFLD, with only NAFLD, only MAFLD. Cox proportional hazard regression was used to estimate multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause and cause-specific mortality. Subgroup analysis were applied in MAFLD patients. Results: The weighted prevalence of MAFLD and NAFLD was relatively 27.4 and 27.9%. Participants with NAFLD or MAFLD were largely overlapped (weighted Cohen's kappa coefficient 0.76). MAFLD increased the overall risk for total mortality in a greater magnitude than NAFLD [HR 2.07 (95% CI 1.86, 2.29) vs. 1.47 (1.20, 1.79)], However, the difference was non-significant after metabolic parameters were adjusted. Risks for cardiovascular, neoplasm, and diabetes-related mortality were similar between MAFLD and NAFLD. Referring to individuals without both NAFLD and MAFLD, individuals with only NAFLD showed reduced total mortality [HR 0.48 (0.34, 0.68)] and neoplasm mortality [HR 0.46 (0.24, 0.89)] in crude. Nevertheless, individuals with only MAFLD independently increased the risk for total mortality [adjusted HR 1.47 (1.22, 1.77)] and neoplasm mortality [aHR 1.58 (1.09, 2.28)]. The risk for overall mortality in MAFLD was consistent between subgroups except for race-ethnicity and whether secondary to viral hepatitis. Conclusions: Participants with MAFLD or NAFLD were highly concordant. MAFLD showed greater risk for all-cause mortality and equal risk for cause-specific mortality referring to NAFLD. The new terminology excluded participants with lower mortality risk and included participants with higher risk. Drug development for MAFLD should consider ethnic differences.