Are there outcome differences between NAFLD and metabolic-associated fatty liver disease?

Given the association of NAFLD with metabolic risks, a name change to MAFLD is proposed. We compared the long-term outcomes of NAFLD and MAFLD.

We included patients with fatty liver disease (FLD) from NHANES III and NHANES 2017-2018 (FLD defined as moderate to severe hepatic steatosis by ultrasound for NHANES III and as having a controlled attenuation parameter ≥285 dB/m for NHANES 2017-2018). NAFLD was defined as FLD without other liver diseases and excess alcohol use. Metabolic-associated fatty liver disease (MAFLD) was defined as FLD and metabolic dysfunction per criteria. All NHANES III participants had linked mortality data through December 31, 2015.

NHANES III participants (n = 12,878): mean age 43.1 years old; 49.5% male; 20.3% with FLD, 16.5% with NAFLD, and 18.1% with MAFLD. NHANES 2017-2018 participants (n = 4328): mean age 48.0 years old; 49.1% male; 36.8% with FLD, 34.2% with NAFLD, and 36.3% with MAFLD. Excellent concordance was noted between MAFLD and NAFLD diagnosis in both data sets (kappa coefficient = 0.83-0.94). Except for components of each definition (e.g., alcohol use for MAFLD), no other major differences in clinical characteristics were noted. During up to 27 years of follow-up (median of 22.8 years), no differences in cumulative all-cause and cause-specific mortality were noted. In addition to the stage of fibrosis, insulin resistance was a predictor of liver mortality in NAFLD, and alcohol-associated liver disease (ALD) was a predictor of mortality in MAFLD.

MAFLD and NAFLD have similar clinical profiles and long-term outcomes. The increased liver-related mortality among NAFLD is driven by insulin resistance, and among MAFLD is primarily driven by ALD.