Le Cornu 2000.

Study characteristics
Methods	RCT. Parallel design with 2 treatment arms. Duration: variable (from pre‐transplant assessment to liver transplant). Location: single centre in the UK.
Participants	Inclusion criteria: adults with end‐stage liver disease accepted for orthotopic liver transplantation, MAMC below 25th percentile. Exclusion criteria: MAMC greater than 25th percentile, fulminant or subacute hepatic failure or malignant disease, requiring acute transplantation, fluid restriction < 500 mL/day, re‐grafts, multiple organ grafts or celiac disease. Number randomised: 82 participants (intervention group, n = 42; control group, n = 40). Gender split: 83% males, 27% females. Age: range 24 ‐ 68 years. Nutritional status: median (range) MAMC (cm) intervention 22.15 (17.6 ‐ 26.2); control 23.2 (17.2 ‐ 26.8).
Interventions	Intervention: participants received dietary advice and ONS in the form of a supplement of a calorie‐dense enteral feed taken daily (in addition to standard dietary advice) until transplantation. Control: participants received dietary advice alone in the form of standard dietetic advice. Standard dietary advice consisted of a dietary recall after which patients were advised on how to adapt their usual dietary intake to increase energy intake and achieve or maintain a moderate protein intake.
Outcomes	Nutritional status (upper arm anthropometric measurements and handgrip strength), dietary intake was calculated from 5‐day food diaries. Post‐transplant: 30‐day mortality, 6‐month mortality, length of stay in ICU, time spent on ventilator, septic complications, major non‐infectious complications, frequency and severity of rejections.
Publication details	Language: English. Funding: no funding, products were supplied by Nutricia. Publication status: peer‐reviewed journal.
Notes	Authors report that, for the supplemented group, there was a statistically significant increase in MAC, grip strength and MAMC between trial entry and the appointment nearest transplant or death. For the control group, there was also a statistically significant improvement in MAC and MAMC, but no change in grip strength. We emailed the authors to ask for the data, but they replied that they do not have the data anymore. Dietary intake was only measured in a few 10 randomly selected (5 in each group) participants. Dietary intake increased from 1840 kcal at entry to the trial to 2395 kcal at transplant in 5 randomly selected participants in the supplemented group and from 2473 tot 2718 in 5 participants in the control group. Data on dietary intake not entered in the review due to small numbers. Authors report pre‐transplant mortality, post‐transplant mortality, and total mortality. As the primary goal of the study was to study the effects of nutritional support on mortality, we report combined mortality.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Not mentioned.
Allocation concealment (selection bias)	Low risk	Randomisation was done by using sealed envelopes selected by a person other than the trial coordinator.
Blinding (performance bias and detection bias) Clinical outcomes	Low risk	The study was unblinded, but is unlikely that this will have influenced primary endpoints such as mortality.
Blinding (performance bias and detection bias) Functional outcomes	High risk	The study was unblinded, functional outcomes could have been influenced by lack of blinding.
Blinding (performance bias and detection bias) Nutritional outcomes	High risk	The study was unblinded, nutritional outcomes could have been influenced by lack of blinding.
Blinding of participants and personnel (performance bias) All outcomes	High risk	Not blinded and likely that researchers and participants were aware of group allocation as this was a nutritional intervention. It is possible that assessment of some outcomes was influenced by lack of blinding
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Judged to be unclear because low risk for clinical outcomes and high risk for functional and nutritional outcomes.
Incomplete outcome data (attrition bias) All outcomes	Low risk	Mortality (primary outcome) was n = 7 (17.5%) in the control group and n = 2 (5%) in the intervention group. Reasons for death are clearly described.
Selective reporting (reporting bias)	High risk	No study protocol identified, thus unable to judge whether all planned outcomes were reported. Unable to interpret outcomes, as results were presented as global description. Quote: "when all diagnoses were considered together, most of the biochemical parameters measured at the appointment before transplantation or death were similar for the two groups" (except for serum phosphate). Outcome data are missing; although described as improvement this can not be verified as no data are given in the manuscript.
Other bias	Low risk	Similar baseline characteristics at inclusion in the study.