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University of Virginia Health System

Nutrition Support E-Journal Club

November-December 2010



The Fall seemed to flash by this year and the cold weather is already upon us (well, cold for Virginia).  We attended the Virginia ASPEN chapter conference (VASPEN) in early November and heard some great speakers.  We also made time for journal club before we were distracted by the turkey, stuffing and pumpkin pie.  All of us here at UVA wish our past trainees and e-journal club readers a wonderful and safe holiday season.

December Citation: 

Kawamura E, Habu D, Morikawa H, et al.  A randomized pilot trial of oral branched-chain amino acids in early cirrhosis: validation using prognostic markers for pre-liver transplant status.  Liver Transpl. 2009;15(7):790-797.


This was a randomized, open-label pilot study of oral branched-chain amino acid (BCAA) granules compared with no treatment in 56 patients with Child's class A cirrhosis.  Subjects received either 4.15 gm BCAA/day (952 mg isoleucine, 1904 mg leucine, 1144 mg valine) along with instruction for a "cirrhotic diet" (25-35 kcal/kg & protein intake of1.0-1.2 g/kg [including 12.45 g/day BCAA in the BCAA group]), or diet instruction for cirrhotic diet alone.

The primary endpoint of the study was the incidence of cirrhosis-related complications including the appearance of hepatocellular carcinoma (HCC), ascites, esophagogastric varices, and hepatic encephalopathy.  Secondary endpoints were defined as the need for an albumin infusion for ascites, endoscopic sclerotherapy/ligation for varices, open surgery, interventional radiological procedures, or percutaneous local ablation for HCC or parenteral BCAAs for hepatic encephalopathy.  The investigators reported annual changes in Child-Turcotte-Pugh (CTP) score, Model for End-Stage Liver Disease (MELD) score, asialoscintigraphic clearance index and labs as the difference between the first and last result divided by the time interval in years.

Inclusion and Exclusion Criteria were:

Inclusion criteria:

  • Age 20 to 75 years
  • Child class A cirrhosis
  • Hepatitis C virus, hepatitis B virus, or alcohol-related cirrhosis.

Exclusion criteria:

  • Etiology of cirrhosis other than inclusion (extremely low prevalence in Japan)
  • Previous albumin infusion at least once per week for 1 month or longer
  • A history of oral BCAA supplementation
  • Dietary protein restriction for 6 months or longer
  • Previous major complications of cirrhosis such as HCC, ascites, esophagogastric varices, or hepatic encephalopathy
  • History of other nonhepatic major diseases

Major Results reported by authors:

Fifty patients completed the protocol and were included in the final analysis. The mean duration of BCAA therapy was 3.2 years (range, 1.0-6.3 years). The authors reported that the mean annual change in MELD score, CTP score, asialoscintigraphic clearance index, and serum bilirubin level was significantly smaller in the BCAA group than the control group.  The mean annual change in the serum albumin level was significantly greater in the BCAA group than in the control group (0.07 ± 0.13 versus -0.02 ± 0.19 g/dL, P = 0.005).

The cumulative incidence of overall major cirrhotic complications was significantly reduced in the BCAA group.  The BCAA group had a 14.8% cumulative incidence of major cirrhotic complications (4 of 27 patients) compared to 30.4% (7 of 23 patients) in the control group at 3 years (p=0.43).  Among the individual complications, only ascites was significantly lower in the BCAA group.  The difference between the incidence of varices and HCC was not significantly different between the groups, and no patient developed encephalopathy.

Author's Conclusions:

The authors concluded that early interventional oral BCAAs might prolong the liver transplant waiting period by preserving hepatic reserve in cirrhosis. A larger multicenter trial is warranted to confirm these findings.


This is a study with a novel approach - that of providing long term BCAA supplements to patients with mild liver disease, prior to the development of major complications.  The research provided some intriguing results, but has a number of significant limitations.  This was not a placebo controlled study, which introduces the possibility of a placebo effect.  Patients taking a product that they believe will improve their health could alter other behaviors, such as physical activity or food intake that leads to beneficial effects on the course of their disease.  Another limitation is that this was only a pilot study, and therefore had a small sample size which would be more likely to be affected by chance.  Finally, there was no attempt to quantify what patients actually consumed of their "cirrhotic diet."


One aspect of the study that deserves scrutiny is the use of "mean annual change" to report factors such as MELD score and labs, rather than the actual lab values before and after the study.  Although the amount of annual change may have been significantly different from each other, the amount of change was so small that the final lab values do not appear to be significantly different between the groups.  In the case of MELD score at the end of one year, the BCAA group would be 6.82, while MELD in the control group would be 7.1; not significantly, or clinically different.  The other values reported as statistically significant also appear to be relatively modest changes, and it is unclear if there were real differences in the values of these labs and scores between the groups at the end of the study.


The significant reductions in cumulative complications, primarily from a reduction in ascites, are a potentially clinically important result.  A delay in the accrual of the complications of cirrhosis would have substantial ramifications for the quality of life for these patients as well as the use of healthcare and transplant resources; ascites in particular is associated with a decrease in oral intake due to gastric compression from fluid.  

We also discussed the strictly nutritional aspects of this study.  All patients received a relatively low protein diet which has no known benefit, and may only serve to impair the body's limited ability for hepatic regeneration in early cirrhosis.  The group receiving the BCAA supplement may simply have had the benefit of more appropriate nitrogen intake.  Ideally, the control group would receive a placebo such as whey or soy protein to control for the potentially beneficial effect of adequate nutrition in patients with early cirrhosis.  The small size, unblinded, non-isonitrogenous nature, and not based on intention to treat design, necessitates that this study be repeated.

Our Take Home messages:

The results of this pilot study justify a larger placebo-controlled trial to investigate the effects of long-term branched-chain amino acid supplementation in early cirrhosis.  Future studies should incorporate a placebo as a less expensive protein supplement that provides similar nitrogen to the BCAA supplement.

Other News:

See our website: http://www.ginutrition.virginia.edu/ for:

Upcoming Webinars for Spring/Summer 2011:

  • January 18: Refeeding the Malnourished Patient--Carol Parrish, MS, RD
  • March 15: Non-Responsive Celiac Disease--Sheila Crowe, MD
  • April 12: Enteral Nutrition in the Critically Ill Pediatric Patient--Ana Abad-Jorge, MS, RD, CNSC
  • May 17: Gastric versus Jejunal Feeding: Combining Data and Clinical Judgement--Joe Krenitsky, MS, RD
  • June 14: Small Bowel Bacterial Overgrowth--Carol Parrish, MS, RD
  • July 19: Feeding the Post-SurgicalPatient--Kate Willcutts, MS, RD, CNSC

Latest Practical Gastroenterology articles:

  • Matarese L. Nutrition Interventions Before and After Adult Intestinal Transplantation: The Pittsburgh Experience. Practical Gastroenterology 2010;XXXIV(11):11-26.
  • Willcutts K. Pre-op NPO and Traditional Post-op Diet Advancement: Time to Move On. Practical Gastroenterology 2010;XXXIV(12):16.

Joe Krenitsky MS, RD

Carol Rees Parrish MS, RD

PS - Please feel free to forward this on to friends and colleagues.