The Role of Branched-Chain Amino Acid Supplementation in Combination with Locoregional Treatments for Hepatocellular Carcinoma: Systematic Review and Meta-Analysis

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Background: Branched-chain amino acid (BCAA) supplementation has been linked with favorable outcomes in patients undergoing surgical or palliative treatments for hepatocellular carcinoma (HCC). To date, there has been no systematic review investigating the value of BCAA supplementation in HCC patients undergoing locoregional therapies.

Materials and methods: A systematic search of the literature was performed across five databases/registries using a detailed search algorithm according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement. The search was conducted on March 23, 2022.

Results: Sixteen studies with a total of 1594 patients were analyzed. Most patients were male (64.6%) with a mean age of 68.2 ± 4.1 years, Child-Pugh score A (67.9%) and stage II disease (40.0%). Locoregional therapy consisted of radiofrequency ablation, transarterial chemoembolization or hepatic artery infusion chemotherapy. BCAA supplementation was in the form of BCAA granules or BCAA-enriched nutrient. Most studies reported improved albumin levels, non-protein respiratory quotient and quality of life in the BCAA group. Results pertaining to other outcomes including overall survival, recurrence rate, and Child-Pugh score were variable. Meta-analysis showed significantly higher levels of post-treatment serum albumin in the BCAA group (SMD = 0.54, 95% CI 0.20-0.87) but no significant differences in mortality rate (RR = 0.81, 95% CI: 0.65-1.02) and AST (SMD = -0.13, 95% CI: -0.43-0.18).

Conclusion: BCAA supplementation is associated with higher post-treatment albumin levels. There are currently not sufficient data to support additional benefits. Further studies are needed to elucidate their value.

Keywords: amino acids; cancer; cirrhosis; hepatocellular carcinoma; interventional radiology; liver cancer; nutrition; supplements.