Update in lean metabolic dysfunction-associated steatotic liver disease

Area of Science:

• Hepatology and Gastroenterology
• Metabolic and Cardiovascular Diseases

Background:

• A new nomenclature defines metabolic dysfunction-associated steatotic liver disease (MASLD), previously NAFLD/MAFLD, incorporating cardiometabolic criteria.
• While extensively studied in overweight individuals, MASLD affects approximately 10%-15% of lean populations, with poorly understood pathogenesis.

Purpose of the Study:

• To systematically review the literature on diagnosis, pathogenesis, characteristics, and prognosis of MASLD in lean individuals.
• To interpret the implications of new nomenclature criteria for lean MASLD patients.

Main Methods:

• Comprehensive literature search of PubMed and Google Scholar (2012-2023) for lean NAFLD, MAFLD, or MASLD studies.
• Inclusion of original articles on adults (≥18 years) with lean BMI (WHO criteria: ≤25 kg/m² general, ≤23 kg/m² Asian).

Main Results:

• Prevalence of lean NAFLD varied widely (3.8%-34.1%); pathogenesis involves genetic, epigenetic, and metabolic factors.
• Common risk factors include metabolic syndrome, hypertension, and type 2 diabetes mellitus, with varied prevalence.
• Fibrosis-4 index outperformed NAFLD fibrosis score; lifestyle modifications improved steatosis and cardiometabolic profiles, but lean patients had a worse prognosis than overweight counterparts.

Conclusions:

• MASLD pathogenesis is multifactorial (epigenetic, genetic, metabolic), with results varying by population, gender, and age.
• Limited clinical practice guidelines exist for lean patients.
• Standardizing results for lean steatotic liver disease requires future studies using the new MASLD nomenclature.