Parenteral nutrition with branched-chain amino acids in hepatic encephalopathy. A meta-analysis

Meta-analytic methods were applied to review clinical trials published in English that have assessed the efficacy of parenteral nutrition for cirrhotic patients with acute hepatic encephalopathy. Modified amino acid solutions containing increased amounts of branched-chain amino acids were used as part of the treatment regimen in all studies. Pooled analysis of five randomized controlled studies showed a highly significant improvement in mental recovery (p less than 0.001) from high-grade encephalopathy over follow-up times varying from 5 to 14 days. The significance level of the treatment effect did not change when the analysis was repeated using alternative methods of counting and attributing events in these trials. Sharp differences in direction of treatment effect precluded pooling case fatality data. Two studies reported an increased risk of death in the treatment group. Two others showed a clear benefit from administration of parenteral nutrition: the aggregate relative risk reduction was 0.59 (95% confidence interval: 0.23-0.80, p = 0.002). Addition of unpublished data from a third positive study increased the relative risk reduction to 0.82 (p less than 0.0001), and the most conservative interpretation of the published data still yielded a significant reduction in mortality (p = 0.023). However, given the uncertainty about effects on mortality and short follow-up times in all studies, a confirmatory randomized controlled trial with longer follow-up periods is warranted.