Comparison of NAFLD, MAFLD and MASLD characteristics and mortality outcomes in United States adults.

Background & Aims: Following the classification of metabolic dysfunction-associated fatty liver disease (MAFLD), non-alcoholic fatty liver disease (NAFLD) has recently been redefined again as metabolic dysfunction-associated steatotic liver disease (MASLD). However, the distinctions in characteristics and mortality outcomes between NAFLD, MAFLD and MASLD remain unclear.

Methods: We analysed data from 7519 participants in the third National Health and Nutrition Examination Surveys of United States (US) and their linked mortality until 2019. Survey weight-adjusted multivariable Cox proportional model was used to study the mortality over three terms.

Results: The prevalence of NAFLD, MAFLD and MASLD was 18.5%, 19.3% and 20.8%, respectively. Most individuals with NAFLD (94.5%) or MAFLD (100%) can be classified as MASLD, while a relatively low percentage of those with MASLD were also diagnosed with either NAFLD (84.1%) or MAFLD (92.7%). During a median follow-up of 26.9 years, both MAFLD and MASLD were associated with increased risk of all-cause mortality (adjusted hazard ratio [aHR] 1.18, 95% CI 1.04-1.33 and 1.19, 1.06-1.34, respectively), this association was mainly observed in NAFLD-/MASLD+ subgroups. NAFLD was not associated with all-cause mortality. However, all three terms were associated with an increased risk of all-cause mortality in individuals with advanced fibrosis (aHR: 1.71-1.81). Subgroup analyses showed that higher risk of all-cause mortality for both MAFLD and MASLD were observed among older adults (≥65 year), non-Hispanic whites and those without diabetes.

Conclusions: Both MASLD and MALFD were linked to higher all-cause mortality risk, but MASLD identified a greater number of individuals compared to MAFLD.