THE EFFECT OF BRANCHED-CHAIN AMINO ACID ON THE IMPROVEMENT OF SERUM ALBUMIN LEVEL IN CIRRHOTIC PATIENTS WITH ASCITES: A MULTI-CENTER, RANDOMIZED, DOUBLE BLIND, PLACEBO-CONTROLLED TRIAL

초록

Background: Serum albumin (SA) level and survival is very closely related in cirrhotic patients with ascites. Previous studies have suggested the possibility that branched-chain amino acid (BCAA) can increase SA concentration. This is the first placebo-controlled, double-blinded, randomized trial to evaluate whether BCAA could be beneficial to increase SA and improved liver function in cirrhotic patients with ascites. Methods: Patients were randomly assigned to BCAA or placebo and then took the drug for 24 weeks. Stratified randomization was performed to balancing the proportion of patients according to Child-Pugh class. Key inclusion criteria was serum albumin 3.5g/dl or less and patents have grade 1 of ascites at least. Primary endpoint was the change in serum albumin concentration at 24 weeks from baseline. Secondary endpoint was the improvement in liver function, skeletal muscle mass (SMI), quality of life measurement (SF-36) and drug safety. Results: Of the 227 patients who were randomly assigned 83 patients were excluded during follow-up period, and finally, 69 patients in placebo and 75 patients in BCAA group completed the study. In intention-to-treat (ITT) population, SA level at 24 weeks was greatly increased from baseline in both groups, but the amount of change was not different when compared between two groups (p=0.11). However, in per-protocol (PP) population, the change of SA concentration was much greater in BCAA group than in placebo group (0.49±0.43 vs. 0.19±0.42, p<0.001). Similarly, in PP population, the CP score of the BCAA group was significantly improved and both physical component score and mental component score in SF-36 were also improved compared to the placebo group. On the other hand, there were no significant difference in SMI, muscle strength, drug adherence and drug safety in both groups. Of note, the change of SA level is absolutely dependent upon drug adherence. Patients who showed adherence of 80% or more to BCAA significantly increased SA level in both ITT and PP populations. Conclusion: Primary endpoint was not achieved in ITT population, but in PP population, SA level of BCAA group significantly increased compared to placebo group. Especially, patients with 80% or more drug adherence to BCAA during 24 weeks significantly increased serum albumin levels and improved Child-Pugh score.