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www.nature.com/clinicalpractice/gasthep
SYNOPSIS
KEYWORDS branched-chain amino acid,
decompensated cirrhosis, nutrition, survival
BACKGROUND
The primary endpoint was time to the aggravation of hepatic failure (including ascites, peripheral edema and jaundice), the rupture of gastric
or esophageal varices, or the development of
liver cancer or death. Secondary endpoints
included improvement in quality of life.
RESULTS
PRACTICE POINT
www.nature.com/clinicalpractice/gasthep
C O M M E N TA RY
Michael Charlton
BCAA-enriched nutritional supplements are,
theoretically, an appealing approach to the prevention of complications in patients with cirrhosis.
This is especially true in the case of portosystemic
encephalopathy, for which the relatively low
ammoniagenic properties of BCAA-enriched
supplements make obvious physiological sense.
Indeed, there have been several reports of beneficial effects of BCAA supplementation, including
protein sparing and normalization of respiratory
quotients,1,2 as well as clinical improvement of
hepatic encephalopathy.25 Demonstrating an irrefutable clinical benefit of BCAA supplementation
has, however, proven a Sisyphean task.
This study by Muto et al. was preceded by
a large Italian trial6 comparing outcomes in
patients with cirrhosis following a year of
BCAA-enriched nutritional support versus
lactalbumin or maltodextrin dietary supplementation. The primary outcome (a composite
of death, frequency of hospital admission and
duration of hospital stay) was significantly
lower in the BCAA arm than in the lactalbumin
arm. In retrospect, the failure to identify a
single complication (as opposed to a composite
endpoint) lessened the impact of this study. The
withdrawal of patients receiving BCAAs from the
study, owing to poor palatability of the BCAA
supplement, was a key factor in the study losing
power to detect significance in the frequency of
individual outcomes.
The Muto et al. study was different in two
critical aspects. Firstly, BCAA supplements were
formulated into granules, which meant that the
surface area over which BCAAs were able to come
into contact with taste buds was reduced; the
superior palatability of the granules was reflected
in the low dropout rate. Secondly, a much larger
number of patients were included in this study;
the total number exceeded that in all previously
reported BCAA supplement trials combined.
Many clinicians will have read the paper hoping
to see a significant benefit to BCAA supplementation in terms of a clear-cut endpoint; then came
the results. The outcomes that clinicians and
patients care about the mostdeath, encephalopathy, variceal bleeding and the development
of hepatocellular carcinomawere similar
between study groups. There were, however,
Acknowledgments
The synopsis was written
by Rachel Jones,
Associate Editor,
Nature Clinical Practice.
Competing interests
The author declared he has
no competing interests.
Correspondence
Division of Gastroenterology
and Hepatology
Mayo Clinic and Foundation
200 First St S.W.
Rochester
MN 55905
USA
charlton.michael@mayo.edu
Received 10 October 2005
Accepted 18 November 2005
www.nature.com/clinicalpractice
doi:10.1038/ncpgasthep0392
PRACTICE POINT
Branched-chain
amino-acid granules
are useful for the
treatment of cirrhosis
and chronic hepatic
encephalopathy
in patients who
are intolerant to a
standard diet and
unresponsive or
intolerant of lactulose