Overview of randomized clinical trials of oral branched-chain amino acid treatment in chronic hepatic encephalopathy

JPEN J Parenter Enteral Nutr. 1996 Mar-Apr;20(2):159-64. doi: 10.1177/0148607196020002159.


Background: The role of oral branched-chain amino acid supplements in the prevention and treatment of chronic hepatic encephalopathy is not yet established, and conflicting opinions are expressed in authoritative textbooks. We aimed to review and pool the published controlled studies by means of meta-analytical techniques.

Methods: A computerized search of published papers identified nine studies, controlled against placebo, energy, alimentary proteins, or casein. Their quality score was calculated according to the protocol of Chalmers. The value of the portal-systemic encephalopathy index was chosen as main outcome, because of lack of more significant clinical outcomes. To cope with differences in trial design and data presentation, individual data were requested to authors.

Results: After 18 months, we received the individual data of only two studies, thus precluding any meta-analysis. Two studies, accounting for over 60% of total enrolled patients, were in favor of branched-chain amino acids. Their quality score was much better than that of the remaining seven negative small studies, carrying a significant risk of type II error.

Conclusions: Based on the results of the two largest, long-term studies, the use of oral branched-chain amino acids in the prevention and treatment of chronic encephalopathy may only be proposed for patients with advanced cirrhosis, intolerant to alimentary proteins. Large, multicenter, long-term studies, considering more important clinical outcomes, are needed to provide definite answers to an aged question.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adult
  • Aged
  • Amino Acids, Branched-Chain / therapeutic use*
  • Chronic Disease
  • Hepatic Encephalopathy / prevention & control
  • Hepatic Encephalopathy / therapy*
  • Humans
  • Middle Aged
  • Randomized Controlled Trials as Topic*


  • Amino Acids, Branched-Chain