Exercise and nutrition interventions for sarcopenia in cirrhosis: a systematic review and network meta-analysis of randomized controlled trials.

Sarcopenia is highly prevalent and associated with poor outcomes in cirrhotic patients. We aimed to evaluate the efficacy of exercise, protein supplementation, and branched-chain amino acid (BCAA) supplementation in treating cirrhotic sarcopenia. PubMed, Embase, Scopus and the Cochrane Library were searched for randomized controlled trials of exercise, protein supplementation, and/or BCAA supplementation on improving at least one of the sarcopenia features: muscle mass, muscle strength and physical performance. Differences in post- and pre-intervention changes between intervention and control arms were calculated as a standardized mean difference (SMD), with 95% confidence interval (CI). A network meta-analysis (NMA), component NMA, pairwise meta-analysis (PW-MA) of 23 trials comprising 1525 participants were performed. By NMA, combined exercise with protein and BCAA supplementations had the greatest effect on increasing muscle mass (SMD 2.12; 95%CI: 0.59-3.65). Exercise alone or with BCAA/protein supplementation also significantly increased muscle mass, but protein or BCAA supplementation alone did not increase muscle mass. By PW-MA, exercise significantly improved physical performance versus control (SMD 1.43; 95%CI: 0.63-2.17; p < 0.01; I² = 59%) and exercise plus protein supplementation was superior to protein alone (SMD 0.66; 95%CI: 0.26-1.06; p = 0.001; I² = 0%). In the systematic review of effects of BCAA supplementation on muscle strength, its impact was inconclusive. Exercise is the mainstay of sarcopenia treatment in cirrhosis and is most effective at improving muscle mass when combined with protein and BCAA supplementation. Nutritional supplementation alone does not enhance muscle mass. Further well-designed studies are needed to identify the most effective type of exercise.