Background & aims: Metabolic dysfunction-associated fatty liver disease (MAFLD) establishes new criteria for diagnosing fatty liver disease independent of alcohol intake and concomitant viral hepatitis infection. However, the long-term outcomes of patients with MAFLD are sparse. We aimed to describe the characteristics and long-term survival of persons meeting criteria for nonalcoholic fatty liver disease (NAFLD) only (non-MAFLD NAFLD), for both NAFLD and MAFLD (NAFLD-MAFLD), and for MAFLD only (non-NAFLD MAFLD).

Methods: Using data from the Third National Health and Nutrition Examination Survey (NHANES III) 1988-1994, 2997 participants with fatty liver identified via ultrasound were categorized into 3 distinct groups: non-MAFLD NAFLD, NAFLD-MAFLD, and non-NAFLD MAFLD.

Results: Participants in the NAFLD-MAFLD and non-NAFLD MAFLD groups were older, had more metabolic traits and higher mean liver enzymes. Nearly 8% of participants in the non-NAFLD MAFLD group had advanced fibrosis (Fibrosis-4 index >2.67), while only 1.3% and 1.9% in the NAFLD-MAFLD and non-MAFLD NAFLD groups did, respectively (P < .0001). Non-NAFLD MAFLD participants had the highest cumulative incidence of all-cause mortality (26.2%) followed by those with NAFLD-MAFLD then non-MAFLD NAFLD participants (21.1% and 10.6%, respectively; P < .0001). Similar findings were observed for cardiovascular disease-related and other-cause (noncardiovascular disease, noncancer) mortality. Non-NAFLD MAFLD was independently associated with all-cause mortality compared with non-MAFLD NAFLD (adjusted hazard ratio, 2.4; 95% confidence interval, 1.2-4.6; P = .01).

Conclusions: MAFLD criteria identified a significant group of people with more comorbidities and worse prognosis compared with those with NAFLD only. These criteria should be considered in the general population to identify high-risk groups for early interventions.