Discussion
muscle mass, skeletal muscle mass, cirrhosis, sarcopenia, Frailty
SARCOPENIA, CIRRHOSIS, SYNDROME
The main result of this open-label randomized controlled trial was that a 16-week BCAA supplementation was associated with an improvement of LFI in frail Child-Pugh A and B cirrhotic patients. Of note, BCAA treatment resulted in a 36% frailty reversion rate compared to 0% in the control group. Moreover, the administration of BCAA also increased muscle mass and improved the physical component of QoL in these patients.Frailty, a distinct biologic syndrome of decreasing physiologic reserve and increase vulnerability to health stressors, is currently known as a poor prognostic factor in patients with cirrhosis [In the present study, a 16-week enteral nutritional support with BCAA-enriched solution resulted in an improvement of frailty in frail compensated cirrhotic patients. To the best of our knowledge, this study is the first that specifically evaluates the addition of BCAA to the standard-of-care to correct frailty in patients with cirrhosis. We were able to demonstrate that a 16-week of twice daily BCAA supplementation resulted in a significant decrease in the LFI compared to the control group (-0.36 vs. -0.15, P < 0.001). Of note, approximate one-third of patients in the BCAA group had frailty resolution at the end of the trial compared with none in the control group. So far, frailty and sarcopenia, a condition of low muscle mass, quality, and strength, have been documented as an important issue in patients with cirrhosis [In the present study, an improvement of LFI at the end of follow-up was observed not only in the BCAA group but also in the control group. We proposed that an improvement of LFI in the control group could be attributed to the dietary and exercise advice provided during the run-in period. A recent placebo-controlled trial evaluating the role of 12-week BCAA supplementation in cirrhotic patients with sarcopenia has demonstrated that LFI significantly decreased in both the BCAA and control arms at the end of follow-up [Another relevant finding of our study is that, apart from the benefit on frailty and skeletal muscle mass, BCAA supplementation also resulted in an improvement in the QoL. Several studies have demonstrated that QoL was dramatically impaired in patients with cirrhosis, and a poor QoL was associated with an increased risk of unplanned hospitalization and short-term mortality [In the present study, the BCAA group had a significant improvement in serum albumin at week 16, however, there was no significant changes in the Child-Pugh, MELD and MELD-Na scores. This absence of efficacy of BCAA on the staging of cirrhosis could be explained by several reasons. First, our study had a relatively short treatment duration (16 weeks). Meanwhile, previous studies showing an improvement in Child-Pugh or MELD score in cirrhotic patients after BCAA treatment had at least 6 months follow-up period [We acknowledged several limitations in the present study. Firstly, this study was a single-center, open-label study. However, the majority of outcomes in this study were objective, and LFI was assessed by the investigators who were unaware of treatment group. These could reduce biases that may occur in an open-label trial. Secondly, we did not assess changes in muscle mass by computer tomography (CT) scan, which is currently the reference method for muscle mass evaluation in cirrhosis. Hence, a previous study has shown that low SMI as evaluated by BIA was associated with morbidity and mortality in patients with cirrhosis [Despite these limitations, our study provides new insights into the management of cirrhosis. The addition of BCAA for 16 weeks to the standard-of-care was able to improve physical frailty in frail compensated cirrhotic patients. In addition, this intervention also resulted in an increase in muscle mass and the physical component score of QoL in these patients. Future studies are needed in larger cohorts of patients, and to determine the optimal dosage and duration of BCAA supplementation.