LEAN MASLD : Diagnosis, Natural history and Treatment in 2026-Lean MASLD

Video Transcription

Video Summary

The ASLD webinar examined lean MASLD diagnosis, natural history, risk factors, and treatment. Speakers emphasized that BMI alone does not define adiposity or metabolic risk: people with normal BMI may have excess visceral fat, metabolic dysfunction, or impaired muscle function. MASLD diagnosis still requires steatosis and at least one cardiometabolic risk factor, alongside assessment of alcohol use and other causes. Clinicians should distinguish lean body mass from muscle mass and assess sarcopenia through function as well as muscle quantity and quality.<br /><br />Lean MASLD is common and often overlooked. Although affected patients may have fewer metabolic risk factors at baseline, multiple studies report elevated long-term liver and overall mortality, and increased cardiovascular outcomes in some cohorts. Fibrosis stage—not BMI—is a key prognostic factor. FIB-4 may be less reliable in lean patients, making liver stiffness measurement particularly useful.<br /><br />Genetic susceptibility, especially PNPLA3, may contribute to lean MASLD, with stronger evidence in Asian cohorts than in Western populations. Lean patients generally show an intermediate metabolic-risk profile between people without MASLD and patients with overweight or obesity. Visceral fat and low muscle mass may also be important.<br /><br />Available therapies, including resmetirom and semaglutide, appear effective in lean patients, though evidence in very-low-BMI groups remains limited. Treatment should be individualized, with attention to drug interactions, gradual dose escalation and weight loss, and strategies to preserve muscle through adequate protein and exercise. The panel called for weight-agnostic screening, better validation of noninvasive tests in lean populations, and longitudinal research into changes in risk over time.

Keywords

lean MASLD

metabolic dysfunction

visceral fat

sarcopenia

fibrosis stage

FIB-4

liver stiffness measurement

PNPLA3

semaglutide

resmetirom