No convincing evidence that branched-chain amino acids have a beneficial effect on patients with hepatic encephalopathy was identified

Als-Nielsen B, Koretz RL, Gluud LL, Gluud C

Published Online:

January 21, 2009

Hepatic encephalopathy occurs in patients with chronic liver disease or fulminant liver failure and is associated with changes in mental state, ranging from minor signs of altered brain function to deep coma. Treatment with branched-chain amino acids has been proposed to ameliorate the symptoms. When all the identified trials were combined, branched-chain amino acids appeared to have a modest effect in improving encephalopathy. However, this effect was not seen when only trials of high quality were included. Thus, this review did not provide convincing evidence to support the use of branched-chain amino acids for patients with hepatic encephalopathy.

Abstract (click to read)

Background:

Hepatic encephalopathy may be caused by a decreased plasma ratio of branched-chain amino acids (BCAA) to aromatic amino acids. Treatment with BCAA may therefore have a beneficial effect on patients with hepatic encephalopathy.

Objectives:

To evaluate the beneficial and harmful effects of BCAA for patients with hepatic encephalopathy.

Search strategy:

We identified trials through The Cochrane Hepato-Biliary Group Controlled Trials Register (September 2002), (Issue 3, 2002), MEDLINE (1966-2002/09) and EMBASE (1980-2002/05), manual searches of bibliographies and journals, authors of trials, and pharmaceutical companies.

Selection criteria:

Randomised trials comparing BCAA with any kind of control therapy for hepatic encephalopathy were included, regardless of blinding, language, or publication status.

Data collection and analysis:

Trial inclusion and data extraction were made independently by two reviewers. Our primary outcome was improvement of hepatic encephalopathy. Statistical heterogeneity was tested using random effects and fixed effect models. Binary outcomes are reported as risk ratios (RR) based on a random effects model.

Main results:

Eleven randomised trials (556 patients) assessing BCAA versus carbohydrates, neomycin/lactulose, or isonitrogenous control were included. The median number of patients in each trial was 55 (range 22 to 75). Follow-up after treatment was reported in four trials (median 17 days (range 6 to 30 days)). Compared to the control regimens, BCAA significantly increased the number of patients improving from hepatic encephalopathy at the end of treatment (risk ratio (RR) 1.31, 95% confidence interval (CI) 1.04 to 1.66, nine trials). We found no evidence of an effect of BCAA on survival (RR 1.06, 95% CI 0.98 to 1.14, eight trials) or adverse events (RR 0.97, 95% CI 0.41 to 2.31, three trials). Sensitivity analyses indicated that methodological quality had significant impact on the results. We found no evidence of an effect of BCAA on improvement of hepatic encephalopathy in trials with adequate generation of the allocation sequence (RR 1.01, 95% CI 0.84 to 1.23, three trials), adequate allocation concealment (RR 1.09, 95% CI 0.89 to 1.33, five trials), or adequate double-blinding (RR 1.20, 95% CI 0.83 to 1.73, three trials).

Authors' conclusions:

We did not find convincing evidence that BCAA had a significant beneficial effect on patients with hepatic encephalopathy. The trials performed in this field were small with short follow-up and most had low methodological quality.

This record should be cited as:

Als-Nielsen B, Koretz RL, Gluud LL, Gluud C. Branched-chain amino acids for hepatic encephalopathy. Cochrane Database of Systematic Reviews 2003, Issue 2. Art. No.: CD001939. DOI: 10.1002/14651858.CD001939

Assessed as up to date:

September 19, 2002

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Primary Review Group:

Hepato-Biliary Group

Health topics:

Complementary & alternative medicine > Gastroenterology > Liver diseases

Gastroenterology > Liver diseases > General liver disease

Cochrane Summaries^beta

Independent high-quality evidence for health care decision making

No convincing evidence that branched-chain amino acids have a beneficial effect on patients with hepatic encephalopathy was identified

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