Metabolic associated fatty liver disease and sarcopenia additively increase mortality: a real-world study.

Background and aims: Sarcopenia is associated with worse prognosis for non-alcoholic fatty liver disease (NAFLD). However, disease progression in the MAFLD-related sarcopenia is largely unknown. We aimed to clarify the relationship between MAFLD and/or sarcopenia with mortality and liver fibrosis in the real world.

Methods: A total of 13,692 individuals were selected from the third National Health and Nutrition Examination Surveys and linked mortality until December 2019. MAFLD is diagnosed based on a radiologically diagnosed hepatic steatosis and the presence of any one of the following three conditions: overweight/obesity, diabetes mellitus (DM), or metabolic dysregulation. Sarcopenia is defined by weight-adjusted skeletal muscle mass.

Results: The mean age was 43.7 ± 15.97 years, and 47.3% of the individuals were male. MAFLD was diagnosed in 4207/13,692 (30.73%) participants, and the proportion of sarcopenic was 19.42% amongst subjects with MAFLD. The mean follow-up duration was of 23.7 ± 7.62 years. MAFLD (aHR 1.152, 95% CI 1.070-1.241) and sarcopenia (aHR 1.123, 95% CI 1.042-1.210) were related to increased all-cause mortality in MAFLD after adjustment for age, sex, race, marital status, education, and smoking. Stratified analysis revealed that MAFLD and sarcopenia additively increased the risk of mortality (aHR 1.247, 95% CI 1.132-1.373) and liver fibrosis (aOR 2.296, 95% CI 1.718-3.069 assessed by NFS score >0.676; aOR 2.218, 95% CI 1.788-2.752 assessed by FIB-4 score >1.3) in fully adjusted models (P < 0.001 for all).

Conclusion: Sarcopenia in individuals with MAFLD portends increased mortality and significant liver fibrosis. Novel therapeutic strategies targeting at increasing skeletal muscle mass should be explored for patients with MAFLD.