1Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, Virginia, USA.
2Center for Liver Disease, Department of Medicine, Inova Fairfax Medical Campus, Falls Church, Virginia, USA.
3Inova Medicine, Inova Health System, Falls Church, Virginia, USA.
4Center for Outcomes Research in Liver Diseases, Washington, DC, USA.
Background: 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.
Methods: 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.
Results: 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.
Conclusions: 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.