Systematic review with meta-analysis: branched-chain amino acid supplementation in liver disease

Anne M van Dijk*, Alexandra S Bruins Slot, Piero Portincasa, Sebastiaan N Siegerink, Najiba Chargi, Carina J R Verstraete, Joep de Bruijne, Frank P Vleggaar, Karel J van Erpecum

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

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Abstract

BACKGROUND: Dietary supplementation with branched-chain amino acids (BCAA) is often used in cirrhotic patients to improve nutritional status. We wanted to explore the evidence for BCAA supplementation in chronic liver disease.

METHODS: We searched MEDLINE and EMBASE for studies with BCAA supplementation with the presence of a disease-control group (placebo or no intervention) using search terms 'liver cirrhosis', 'hepatocellular carcinoma', 'branched chain amino acids' and relevant synonyms. Risk of bias was assessed using ROBINS-I and RoB 2.0 tools. Meta-analyses were performed with a random-effects model. Results were reported following EQUATOR guidelines.

RESULTS: Of 3378 studies screened by title and abstract, 54 were included (34 randomized controlled trials, 5 prospective case-control studies, 13 retrospective case-control studies: in total 2308 patients BCAA supplementation, 2876 disease-controls). Risk of bias was high/serious for almost all studies. According to meta-analyses, long-term (at least 6 months) BCAA supplementation in cirrhotic patients significantly improved event-free survival (p = .008; RR .61 95% CI .42-.88) and tended to improve overall survival (p = .05; RR .58 95% CI .34-1.00). Two retrospective studies suggested the beneficial effects during sorafenib for hepatocellular carcinoma. Available studies reported no beneficial effects or contradictory results of BCAA after other specific therapeutic interventions (resection or radiological interventions for hepatocellular carcinoma, liver transplantation, paracentesis or variceal ligation). No convincing beneficial effects of BCAA supplementation on liver function, nutritional status or quality of life were found. No study reported serious side effects of BCAA.

CONCLUSIONS: Prophylactic BCAA supplementation appears safe and might improve survival in cirrhotic patients.

Original languageEnglish
Article numbere13909
JournalEuropean Journal of Clinical Investigation
Volume53
Issue number3
Early online date17 Nov 2022
DOIs
Publication statusPublished - Mar 2023

Keywords

  • branched-chain amino acids
  • cirrhosis
  • hepatocellular carcinoma
  • liver
  • nutrition

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