Nakaya 2007

Methods	Randomised trial comparing supplements (branched chain amino acids) to no supplements in outpatients with cirrhosis secondary to hepatitis C. Geographical location Japan. Paper published 2005.
Participants	Inclusion criteria: Cirrhosis, anti‐HCV+, albumin < 3.5 gm%. Exclusion criteria: Overt hepatic encephalopathy, uncontrolled variceal bleeding, refractory ascites, renal impairment, prior history poor compliance, hepatocellular carcinoma with overt disease, positive alpha‐fetoprotein, diabetes mellitus on medications, intravenous albumin use. 48 patients (28 men/10 women [10 other dropouts], mean age 68).
Interventions	Intervention group received nutritional supplement (Commercial branched chain amino acid supplement [Amionleban EN® ‐ 13.5 gm protein, 3.5 gm fat, trace minerals and vitamins] 210 kcal/day); Controls received food (9 gm protein, 5 gm fat, 210 kcal/day). Duration therapy 3 months.
Outcomes	Mortality, bilirubin, body weight. Quality of life reported, but not in usable format. Triceps skinfold thickness, midarm muscle circumference, midarm circumference measured but not reported; nitrogen balance change only reported as significant for treatment group but not for control group.
Category of study	Supplements/Medical.
Sample size calculation	Not reported if done.
Full paper or abstract only	Full paper.
Notes	Request for further information sent via e‐mail on September 19, 2011 (nakaya@nutr.med.tokushima‐u.ac.jp); e‐mail address failed. Letter sent via US mail on same day (Yutaka Nakaya, MD, Department of Nutrition and Metabolism, Institute of Health Biosciences, University of Tokushima Graduate School, Tokushima, Japan). Letter dated Novenber 15, 2011 received indicating that the generation of the randomisation scheme was adequate (computer generated based on stratification for "important parameters"), concealment of allocation was adequate (central computer), no sample size calculation was performed and no explanation provided as to why trial was stopped when it was, funding was not obtained and trial conducted by interested investigators. Ascites developed in 1/16 treatment versus 1/15 controls and resolved in 2/3 versus 0/4. Hepatic encephalopathy developed in 0/19 versus 1/19; no patient was encephalopathic at the beginning of the trial. There were no episodes of GI bleeding or infections. 8 different quality of life scores were provided; there were no apparent differences. Data regarding costs and lengths of stay were not collected. There were 5/19 versus 2/19 adverse events in the two arms (in addition to nonsevere ones (fever in one versus nausea in one), there were 4 [death from cerebral bleed, bone fracture, and 2 worsening of ascites] versus 1 [worse encephalopathy] serious adverse events). The weights in the two groups at the beginning/end of the trial were 18.6 (9.0) versus 56.6 (7.7)/59.4 (9.6 SD) versus 57.1 (7.7). The arm muscle circumferences at the beginning/end of the trial were 241.3 (39.6) versus 239.7 (32.5)/244.4 (33.7) versus 243.2 (31.8). Triceps skinfold thicknesses at the beginning/end of the trial were 11.7 (4.4) versus 12.6 (4.5)/12.6 (4.5) versus 13.4 (4.5). New e‐mail address also provided (yutaka‐nakaya@nutr.med.tokushima‐u.ac.jp).
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Computer generated with stratifications for "important parameters" (information from investigator).
Allocation concealment (selection bias)	Low risk	Central randomisation and assignment (information from investigator).
Blinding (performance bias and detection bias) All outcomes	High risk	Not blinded.
Incomplete outcome data (attrition bias) All outcomes	Low risk	Six dropouts in treatment group, 4 dropouts in control group all accounted for.
Selective reporting (reporting bias)	Low risk	Mortality and morbidity outcomes reported.
Other bias	Unclear risk	No external funding; trial conducted by interested investigators. (information from investigator). No sample size calculation (see below).
Intent to treat analysis	High risk	Could not be done.
Baseline imbalance?	Low risk	No differences identified.
Early stopping?	Unclear risk	No sample size calculation was performed (information from investigator) and unknown why stopped.