Cardiovascular Outcomes in Lean Versus Non-Lean Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD): A Systematic Review and Meta-Analysis

This systematic review and meta-analysis is designed to map out the long-term cardiovascular risks associated with "lean" MASLD (Metabolic Dysfunction-Associated Steatotic Liver Disease). Even though cardiovascular disease is the primary driver of mortality across the MASLD spectrum, there is still an active debate in the medical community about whether normal-weight patients face a lower risk or a paradoxically higher risk compared to the classic, non-lean phenotype. Our main goal is to pool data from longitudinal cohort studies to get a definitive, adjusted Hazard Ratio for major adverse cardiovascular events (MACE) and cardiovascular mortality. We also plan to use subgroup and sensitivity analyses to dig into why different studies have come up with conflicting results—looking closely at things like geographic differences and baseline metabolic health. Finally, we will use the GRADE framework to evaluate the overall certainty of the current evidence. Methodologically, we are running a comprehensive search across PubMed, EMBASE, the Cochrane Library, and Scopus from inception through June 2026. Two reviewers will handle study selection, data extraction, and quality appraisal (using the Newcastle-Ottawa Scale) independently in duplicate to minimize errors. Statistically, we are using a DerSimonian-Laird random-effects model to handle the synthesis. Ultimately, we expect this project to provide a clear, reliable risk profile for lean MASLD patients. The data generated should help clinicians better stratify patient risk and update screening guidelines for normal-weight individuals who might otherwise be missed in routine cardiovascular checkups.