• Metabolic dysfunction-related fatty liver disease (MAFLD) is now recognized as a distinct entity from NAFLD, with metabolic dysregulation as the core, and exhibits significant heterogeneity in disease progression.
• Insulin resistance and oxidative stress are common pathways driving MAFLD pathogenesis, while genetic variants such as PNPLA3 I148M and TM6SF2 E167K independently modulate disease risk and progression.
• Adipose tissue dysfunction is a key mechanism in lean MAFLD, leading to ectopic fat deposition and reduced adiponectin levels, contributing to higher mortality risk.
• Three metabolic subtypes (A, B, C) of MAFLD have been identified, with distinct cardiovascular and liver fibrosis progression profiles, enabling risk stratification and personalized intervention.