Changes in Muscle Mass and the Risk of Liver‐Related Events: A Prospective Cohort Study

ABSTRACT Background and Aims Previous studies found that lower muscle mass at baseline was an important risk factor for liver‐related events (LRE), yet evidence on longitudinal muscle mass changes remains limited. This study examines associations between changes in muscle mass and incident LRE. Methods This prospective cohort study included 19 660 participants with baseline and first follow‐up body composition data. Appendicular skeletal muscle mass (ASM) was estimated using bioelectrical impedance analysis and the Janssen equation, and was indexed to body mass index as ASM/BMI. ΔASM/BMI was calculated as ASM/BMI at first follow‐up minus ASM/BMI at baseline. Follow‐up for incident LRE started at the first follow‐up assessment. Cox proportional hazards models, restricted cubic spline analyses, subgroup analyses, competing‐risk models, and sensitivity analyses were performed. Results During a median follow‐up of 9.87 years, 101 incident LRE were identified. In the fully adjusted model, higher ΔASM/BMI was associated with a lower risk of incident LRE. Compared with participants in the lowest tertile, those in the intermediate and highest tertiles had lower LRE risk, with HRs of 0.59 (95% CI, 0.37–0.94) and 0.44 (95% CI, 0.27–0.72), respectively. The association was more pronounced among participants younger than 60 years ( p for interaction = 0.042). Restricted cubic spline analysis showed a significant nonlinear association between ΔASM/BMI and LRE risk (P‐overall = 0.012; p ‐non‐linear = 0.029). Results were generally consistent in competing‐risk, sensitivity, propensity score‐based, and nested case–control analyses. Conclusion Greater preservation or increase in muscle mass was associated with a lower risk of incident LRE, particularly among participants younger than 60 years. These findings support the potential relevance of maintaining muscle mass for liver risk stratification.