Branched-Chain Amino Acid Supplementation and Clinical Outcomes in Liver Cirrhosis: A Propensity Score-Matched Multicenter Retrospective Cohort Study

Purpose: Branched-Chain Amino Acid (BCAA) supplementation has shown benefits in reducing liver cirrhosis complications, improving survival, and potentially lowering hepatocellular carcinoma risk, but evidence on long-term outcomes remains limited. This real-world study evaluates clinical outcomes of liver cirrhosis patients receiving BCAA supplementation. Methods: This retrospective cohort study used the TriNetX US Collaborative Network to identify liver cirrhosis patients aged ≥ 18 years, stratified by BCAA supplementation after diagnosis. Propensity score matching (PSM) balanced cohorts by demographics, body mass index, Model for End-Stage Liver Disease (MELD) score components, and baseline history of cirrhosis complications, including hepatic encephalopathy (HE), sarcopenia, spontaneous bacterial peritonitis (SBP), acute kidney injury (AKI), and falls. Composite and individual outcomes within 5 years were assessed using odds ratios (OR) with 95% confidence intervals (CI). Results: Among 2,176 matched patients per group, BCAA supplementation was associated with lower rates of the composite outcome (OR 0.81, 95% CI: 0.71–0.92), HE (OR 0.63, 95% CI: 0.49–0.79), SBP (OR 0.77, 95% CI: 0.60–0.99), falls (OR 0.64, 95% CI: 0.53–0.78), all-cause emergency room visits (OR 0.56, 95% CI: 0.50–0.64), and hospitalizations (OR 0.68, 95% CI: 0.60–0.76). Liver transplantation occurred more frequently in the BCAA group (OR 1.49, 95% CI: 1.08–2.06). Sarcopenia rates were similar (OR 1.00, 95% CI: 0.42–2.41), while AKI was slightly more frequent (OR 1.13, 95% CI: 1.00–1.28). Subgroup analysis showed greater benefit in viral hepatitis-associated (OR 0.69, 95% CI: 0.53–0.90) and alcohol-associated cirrhosis (OR 0.73, 95% CI: 0.60–0.89), compared to MASLD (OR 0.81, 95% CI: 0.60–1.08). Conclusion: BCAA supplementation was associated with significant reductions in several cirrhosis-related complications, with most benefits observed in viral hepatitis-associated and alcohol-associated cirrhosis.