Lean MAFLD as a distinct phenotype

Lean metabolic dysfunction-associated fatty liver disease (L-MAFLD) challenges the prevailing view that a normal body mass index (BMI) is an indicator of metabolic health. This phenotype is associated with visceral adiposity, sarcopenia and impaired metabolic flexibility and it is characterized by a striking genetic and epigenetic signature. Despite standard anthropometric measurements, L-MAFLD imposes a systemic burden - manifesting as increased liver-related and all-cause mortality - and is linked to varying prevalences of advanced fibrosis, cardiovascular disease, chronic kidney disease, and gastrointestinal malignancies. Histologically, it resembles metabolic dysfunction-associated steatohepatitis, confirming that metabolic dysregulation is the true driver of disease progression. This review presents an emerging, phenotype-first diagnostic and therapeutic approach, integrating recent evidence regarding the epidemiology, pathophysiology, and systemic outcomes of the condition.