Rate and clinical predictors of skeletal muscle loss in patients with cirrhosis

BACKGROUND: Skeletal muscle mass predicts outcomes in cirrhosis and represents a therapeutic target. However, the natural rate of muscle change in this population remains poorly defined. OBJECTIVE: We characterised longitudinal skeletal muscle change and its association with clinical outcomes in cirrhosis. DESIGN: This cohort study enrolled ambulatory adults with cirrhosis awaiting liver transplantation at a tertiary centre who underwent at least two abdominal CT scans between February 2015 and January 2021. Skeletal muscle index (SMI) at L3 was quantified and normalised for height. Annualised percent change in SMI (ΔSMI/year%) was calculated. The primary outcome was waitlist mortality, defined as death or delisting for being too ill for transplantation. RESULTS: Among 364 patients (median age 62 years; 68% male; model for end-stage liver disease-sodium (MELD-Na) 12), the median (IQR) ΔSMI/year% was -1.6% (-7.4 to +3.7). Rapid muscle loss (RML) was defined as the worst quartile of ΔSMI/year% (< -7.4%; n=91). Independent predictors of RML included ascites (OR 1.77, 95% CI 1.00 to 3.12) and higher MELD-Na (OR 1.06, 95% CI 1.00 to 1.13). Cumulative waitlist mortality was significantly higher in patients with RML than in those without RML at 12 months (32% vs 10%) and 24 months (75% vs 27%) (log-rank p<0.001). RML independently predicted waitlist mortality in adjusted Cox models (HR 3.43-3.52). CONCLUSION: Patients with cirrhosis had a median skeletal muscle loss of 1.6%/year. In this cohort, RML independently predicted waitlist mortality and was associated with ascites and MELD-Na. These data could inform effect-size estimates for future trials targeting sarcopenia in cirrhosis with low-to-moderate MELD-Na.