Introduction Metabolic dysfunction–associated steatotic liver disease (MASLD) has traditionally been linked with obesity and metabolic syndrome. However, an emerging subset—lean MASLD—is increasingly recognised, particularly in Asian populations.
Introduction
Metabolic dysfunction–associated steatotic liver disease (MASLD) has traditionally been linked with obesity and metabolic syndrome. However, an emerging subset—lean MASLD—is increasingly recognised, particularly in Asian populations. Despite having a normal body mass index, these patients exhibit metabolic dysfunction and hepatic steatosis. The long-term clinical implications of lean MASLD have remained unclear, with conflicting data regarding whether it represents a milder or equally aggressive phenotype compared to non-lean MASLD.
Problem Statement
Current clinical paradigms often underestimate lean MASLD due to the absence of obesity, leading to delayed diagnosis and risk stratification. There is a major gap in understanding whether lean MASLD carries similar, lower, or higher risks of liver-related events, mortality, and cardiovascular outcomes compared to non-lean MASLD.
Summary
This large multicohort prospective study involving over 180,000 patients across Western and Asian populations provides important clarity. Lean MASLD was associated with significantly higher risks of liver-related events, liver-related mortality, and overall mortality, highlighting a more aggressive hepatic phenotype despite normal BMI. Interestingly, lean MASLD showed similar risks of hepatocellular carcinoma and extrahepatic cancers, but lower cardiovascular disease risk compared to non-lean MASLD.
These findings redefine lean MASLD as a high-risk but under-recognized clinical entity, emphasizing that absence of obesity does not imply a benign course. Clinicians must adopt a metabolic and liver-focused approach rather than BMI-based risk assessment, ensuring early detection, monitoring, and targeted management in this overlooked population.
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