Natural history of lean and non-lean metabolic dysfunction-associated steatotic liver disease.

ABSTRACT

BACKGROUND: Conflicting evidence regarding the prognosis of lean metabolic dysfunction-associated steatotic liver disease (MASLD) has raised substantial questions. AIM: This study aimed to elucidate the prognosis of lean MASLD by conducting a comprehensive analysis of a vast Asian cohort. METHODS: This study used a nationwide, population-based database and analyzed 2.9 million patients. The primary endpoints were liver-related events (LREs) and cardiovascular events (CVEs) in patients with lean MASLD, non-lean MASLD, and normal liver control groups. RESULTS: The median observation period was 4.2 years. The 5-year incidence values of LREs in the lean MASLD, non-lean MASLD, and normal liver control groups were 0.065%, 0.039%, and 0.006%, respectively. The LRE risk of lean MASLD was significantly higher than that of normal liver control (adjusted hazard ratio [aHR] 5.94, 95% confidence interval [CI] 3.95-8.92) but comparable to that of non-lean MASLD (aHR 1.35, 95% CI 0.87-2.08). By contrast, for CVEs, the non-lean MASLD group exhibited a higher 5-year cumulative incidence rate (0.779%) than the lean MASLD (0.600%) and normal liver control (0.254%) groups. The lean MASLD group had a reduced risk of CVEs compared with the non-lean MASLD group (aHR, 0.73; 95% CI 0.64-0.84), and comparable risk of CVEs to the normal liver control group (aHR, 0.99; 95% CI 0.88-1.12). CONCLUSION: Lean MASLD exhibits a similar LRE risk and a lower CVE risk to non-lean MASLD. Therefore, follow-up and treatment strategies should be tailored to the specific MASLD condition.