ONC: Branched Chain Amino Acids (2006)

Citation:
 
Study Design:
Class:
- Click here for explanation of classification scheme.
Quality Rating:
Research Purpose:
To examine the possibility of maintaining a favorable state of nutrition by outpatient administration of branched-chain amino acid (BCAA) granules. 
Inclusion Criteria:
  • patients who had undergone possibly curative hepatic resection for primary HCC with gross liver cirrhosis and kept low levels of serum albumin (<3.5 g/dL) 2 to 3 weeks after the procedure
Exclusion Criteria:
  • tumor recurrence
Description of Study Protocol:

Recruitment

  • patients in accordance with the inclusion/exclusion criteria were recruited between January 1999 and May 2002

Design

  • Patients were randomized into two groups: those who received BCAA supplementation and a control group. 
  • Control patients ate their usual meals.
  • BCAA group drank 4.74 g of Livact three times a day in addition to their usual meals for 1 year. 

Livact composition:  4.74 g = 4 g BCAA (l-valine, 1144 mg; l-leucine, 1904 mg; l-isoleucine, 952 mg)

Blinding used (if applicable)

  • unclear. 

Intervention (if applicable)

Not applicable

Statistical Analysis

  • data were analyzed by chi-squared test, Mann-Whitney U test, repeated measures analysis of variance, or unpaired Students' t test. 
  • P < 0.05 was considered statistically significant. 
Data Collection Summary:

Timing of Measurements

  • After discharge from hospital, pts were followed up every 2 weeks for 1 year. 
  • Clinical features and biochemical parameters were measured at 1, 3, 6, 9, and 12 mo. 
  • Tumor recurrence was studied at 3 mo intervals

Dependent Variables

  • Variable 1: brief description (how measured?)
  • Variable 2: brief description (how measured?)
  • etc

Independent Variables

 

Control Variables

 

Description of Actual Data Sample:

Initial N: BCAA, n=21; Control, n=22

Attrition (final N): BCAA, n=19; Control, n=22

Age:

  • BCAA, 66.5 +/- 4.5 (male:female, 17:4)
  • Control, 64.3 +/- 9.1 (male:female, 17:5)

Ethnicity:

  • unknown

Anthropometrics

  • pts were comparable in terms of age, sex, underlying liver disease, Child-Pugh grade, tumor size and TNM stage, and extent of liver resection (table 1)

Location:

Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama Japan. 

Summary of Results:

Findings:

  • Of the 21 patients in the BCAA group, 2 patients withdrew due to tumor recurrence
  • No significant difference in terms of Karnovsky's performance score or an anthropometric measurement, specifically weight.
  • No significant difference in oral intake between the groups.
  • No significant difference in the frequency of ascites and edema between the groups. 
  • No significant difference in hemoglobin concentration, platelet count, or liver function. 
  • Serum albumin returned to preoperative levels after 6 months in the BCAA group and after 9 months in the control group.

For specific bar graphs, please refer to the original article. 

 

Author Conclusion:
"BCAA supplementation after hepatectomy promotes rapid improvement in protein metabolism and inhibits progression to liver cirrhosis.  Administration of BCAA after hepatectomy is considered beneficial to a patient's nutritional status."
Funding Source:
University/Hospital: Yokohama City Univesity
Reviewer Comments:
  • it is unclear whether there was blinding with patients and clinicians
  • assessment of food intake and compliance is not described
  • results are provided in predominantly bar graph format and difficult to determine exact numbers, must rely on author's commentary. 
Quality Criteria Checklist: Primary Research
Relevance Questions
  1. Would implementing the studied intervention or procedure (if found successful) result in improved outcomes for the patients/clients/population group? (Not Applicable for some epidemiological studies) Yes
  2. Did the authors study an outcome (dependent variable) or topic that the patients/clients/population group would care about? Yes
  3. Is the focus of the intervention or procedure (independent variable) or topic of study a common issue of concern to dieteticspractice? Yes
  4. Is the intervention or procedure feasible? (NA for some epidemiological studies) Yes
 
Validity Questions
1. Was the research question clearly stated? Yes
  1.1. Was (were) the specific intervention(s) or procedure(s) [independent variable(s)] identified? Yes
  1.2. Was (were) the outcome(s) [dependent variable(s)] clearly indicated? Yes
  1.3. Were the target population and setting specified? Yes
2. Was the selection of study subjects/patients free from bias? Yes
  2.1. Were inclusion/exclusion criteria specified (e.g., risk, point in disease progression, diagnostic or prognosis criteria), and with sufficient detail and without omitting criteria critical to the study? Yes
  2.2. Were criteria applied equally to all study groups? Yes
  2.3. Were health, demographics, and other characteristics of subjects described? Yes
  2.4. Were the subjects/patients a representative sample of the relevant population? Yes
3. Were study groups comparable? Yes
  3.1. Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT) Yes
  3.2. Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline? Yes
  3.3. Were concurrent controls or comparisons used? (Concurrent preferred over historical control or comparison groups.) Yes
  3.4. If cohort study or cross-sectional study, were groups comparable on important confounding factors and/or were preexisting differences accounted for by using appropriate adjustments in statistical analysis? N/A
  3.5. If case control study, were potential confounding factors comparable for cases and controls? (If case series or trial with subjects serving as own control, this criterion is not applicable.) N/A
  3.6. If diagnostic test, was there an independent blind comparison with an appropriate reference standard (e.g., "gold standard")? N/A
4. Was method of handling withdrawals described? Yes
  4.1. Were follow-up methods described and the same for all groups? Yes
  4.2. Was the number, characteristics of withdrawals (i.e., dropouts, lost to follow up, attrition rate) and/or response rate (cross-sectional studies) described for each group? (Follow up goal for a strong study is 80%.) Yes
  4.3. Were all enrolled subjects/patients (in the original sample) accounted for? Yes
  4.4. Were reasons for withdrawals similar across groups? Yes
  4.5. If diagnostic test, was decision to perform reference test not dependent on results of test under study? N/A
5. Was blinding used to prevent introduction of bias? ???
  5.1. In intervention study, were subjects, clinicians/practitioners, and investigators blinded to treatment group, as appropriate? ???
  5.2. Were data collectors blinded for outcomes assessment? (If outcome is measured using an objective test, such as a lab value, this criterion is assumed to be met.) ???
  5.3. In cohort study or cross-sectional study, were measurements of outcomes and risk factors blinded? N/A
  5.4. In case control study, was case definition explicit and case ascertainment not influenced by exposure status? N/A
  5.5. In diagnostic study, were test results blinded to patient history and other test results? N/A
6. Were intervention/therapeutic regimens/exposure factor or procedure and any comparison(s) described in detail? Were interveningfactors described? Yes
  6.1. In RCT or other intervention trial, were protocols described for all regimens studied? Yes
  6.2. In observational study, were interventions, study settings, and clinicians/provider described? N/A
  6.3. Was the intensity and duration of the intervention or exposure factor sufficient to produce a meaningful effect? Yes
  6.4. Was the amount of exposure and, if relevant, subject/patient compliance measured? Yes
  6.5. Were co-interventions (e.g., ancillary treatments, other therapies) described? No
  6.6. Were extra or unplanned treatments described? No
  6.7. Was the information for 6.4, 6.5, and 6.6 assessed the same way for all groups? N/A
  6.8. In diagnostic study, were details of test administration and replication sufficient? N/A
7. Were outcomes clearly defined and the measurements valid and reliable? Yes
  7.1. Were primary and secondary endpoints described and relevant to the question? Yes
  7.2. Were nutrition measures appropriate to question and outcomes of concern? Yes
  7.3. Was the period of follow-up long enough for important outcome(s) to occur? Yes
  7.4. Were the observations and measurements based on standard, valid, and reliable data collection instruments/tests/procedures? Yes
  7.5. Was the measurement of effect at an appropriate level of precision? Yes
  7.6. Were other factors accounted for (measured) that could affect outcomes? No
  7.7. Were the measurements conducted consistently across groups? Yes
8. Was the statistical analysis appropriate for the study design and type of outcome indicators? Yes
  8.1. Were statistical analyses adequately described and the results reported appropriately? Yes
  8.2. Were correct statistical tests used and assumptions of test not violated? Yes
  8.3. Were statistics reported with levels of significance and/or confidence intervals? Yes
  8.4. Was "intent to treat" analysis of outcomes done (and as appropriate, was there an analysis of outcomes for those maximally exposed or a dose-response analysis)? N/A
  8.5. Were adequate adjustments made for effects of confounding factors that might have affected the outcomes (e.g., multivariate analyses)? ???
  8.6. Was clinical significance as well as statistical significance reported? Yes
  8.7. If negative findings, was a power calculation reported to address type 2 error? N/A
9. Are conclusions supported by results with biases and limitations taken into consideration? ???
  9.1. Is there a discussion of findings? Yes
  9.2. Are biases and study limitations identified and discussed? No
10. Is bias due to study's funding or sponsorship unlikely? ???
  10.1. Were sources of funding and investigators' affiliations described? No
  10.2. Was the study free from apparent conflict of interest? ???