Branched-chain amino acids for hepatic encephalopathy.
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.


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


METHODS
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.


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


METHODS
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.


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).


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.
Als-Nielsen
B
B
Cochrane Hepato-Biliary Group, Copenhagen Trial Unit, Centre for Clinical Intervention Research, Copenhagen University Hospital, H:S Rigshospitalet, Dep. 7102, Blegdamsvej 9, Copenhagen, Denmark. Bodil.a@ctu.rh.dk
Koretz
R L
RL
Kjaergard
L L
LL
Gluud
C
C
D000597:Amino Acids, Branched-Chain / Q000627:therapeutic use*; D005260:Female; D006501:Hepatic Encephalopathy / Q000188:drug therapy*; D006801:Humans; D008297:Male; D016032:Randomized Controlled Trials as Topic
D000597:Amino Acids, Branched-Chain