Lerut 2008.

Methods	Trial design: randomised, double‐blinded, placebo‐controlled, single‐centre clinical trial Mean follow‐up: total: 48 months (range: 12 to 84 months) Study duration: 5 years from randomisation Language: English Type of information: journal article Judgement on quality: high risk of bias
Participants	Setting: Université Catholique de Louvain Cliniques, Universitaires Saint‐Luc, Brussels, Belgium Allocation of participants: 156 participants, 78 allocated to Intervention A, 78 allocated to Intervention B Sex ratio: total: 98 (62.8%) males, 58 (37.2%) females Intervention A: 50 (64.1%) males, 28 (35.9%) females Intervention B: 48 (61.5%) males, 30 (38.5%) females Mean age: total: not reported Intervention A: 52.1 ± 13.0 Intervention B: 49.0 ± 12.7 Indication (no. (%)): HCV cirrhosis: total: 35 (22.4%), Intervention A: 21 (26.9%), Intervention B: 14 (17.9%) Cholestatic disease: total: 18 (11.5%), Intervention A: 10 (12.8%), Intervention B: 8 (10.3%) Vascular disease: total: 3 (1.9%), Intervention A: 3 (3.8%), Intervention B: 0 (0%) Metabolic disease: total: 9 (5.8%), Intervention A: 2 (2.6%), Intervention B: 7 (9.0%) Benign tumour: total: 9 (5.8%), Intervention A: 4 (5.1%), Intervention B: 5 (6.4%) Hepatocellular carcinoma: total: 37 (23.7%), Intervention A: 19 (24.4%), Intervention B: 18 (23.1%) Fulminant failure: total: 22 (14.1%), Intervention A: 9 (11.5%), Intervention B: 13 (16.7%) Type of donor: living and deceased donors Inclusion criteria: adult liver transplant recipient Exclusion criteria: unfavourable oncological diagnosis, already included in another RCT Other: Ischaemia time: Intervention A: 603+/‐231 minutes, Intervention B: 682+/‐204 minutes Artificial organ support: total: 11 (7.1%), Intervention A: 10 (12.8%), Intervention B: 1 (1.3%) Right liver living liver transplantation: total: 9 (5.8%), Intervention A: 0 (0%), Intervention B: 9 (11.5%) Baseline imbalance: the intervention groups differ significantly in relation to ischaemia time, living donor liver transplantation and artificial organ support.
Interventions	Intervention A: matched placebo Intervention B: methylprednisolone started at 16 mg then tapered every 14 days by 4 mg from day 21 to stop at day 64 Concomitant immunosuppression: Tacrolimus: aiming for trough level of 5 to 8 ng/mL Hydrocortisone: 1000 mg intraoperatively
Outcomes	Mortality, graft loss, acute rejection, glucocorticosteroid‐resistant rejection, chronic rejection, infection, bacterial infection, viral infection, fungal infection, CMV infection, bilirubin, ALT, GGT, post‐transplant lymphoproliferative disorder (PTLD), renal insufficiency, diabetes mellitus, new‐onset diabetes after transplantation (NODAT), hyperuricaemia, hypercholesterolaemia, hypertension, de novo hypertension, osseo‐muscular pain or fractures, cataract, Karnofsky index, recurrent hepatitis C, intrahepatic biliary problems
Notes	Cross‐over between intervention arms: no Sample size calculation: yes Sources of funding: the Belgian FRSM, Astellas Pharma, Munchen, Germany
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Quote from the publication: "The patients were randomized, 1:1 into our previously used IS scheme consisting of TAC‐low dose and short‐term steroids (TAC‐ST; n 78) or into TAC‐placebo (TAC‐PL; n 78)." Comment: Generation of randomisation sequence not described
Allocation concealment (selection bias)	Low risk	Quote from the publication: "The randomization was done at the end of surgery using serially numbered, sealed, and opaque envelopes." Comment: Adequate allocation concealment using sealed, opaque envelopes
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Quote from the publication: "Steroids and placebos were administered in identical plastic containers containing a similar number of identical, opaque capsules. Their number, corresponding to a reducing dose that covered a post‐LT period of 64 days, was prepared by an independent pharmacist." Quote from the publication: "All patients, health care providers, and outcome assessor teams were blinded until the 12‐month analysis was complete." Comment: Double‐blinded trial, both participants and medical staff blinded to treatment. Adequate placebo using identical opaque capsules
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Quote from the publication: "All patients, health care providers, and outcome assessor teams were blinded until the 12‐month analysis was complete." Comment: All outcome assessors including pathologists blinded
Incomplete outcome data (attrition bias)	Low risk	Quote from the publication: "There were no dropouts or withdrawals in either intervention group." Quote from the 2014 publication: "Five‐year biopsy was done in 112 (89.6%) patients (Table 2). Twelve (9.6%) patients with stable, normal liver tests refused a biopsy (n = 11); once (0.8%) tissue material was insufficient for analysis." No missing outcome data, no withdrawals. Data missing from participants refusing liver biopsy in the five‐year follow‐up unlikely to affect outcome results
Selective reporting (reporting bias)	Low risk	Comment: All outcomes appear to be fully reported
Other bias	High risk	Quote from the publication: "This work was supported by a grant from the Belgian FRSM (3.4548.02). Astellas Pharma, Munchen, Germany provided the randomization envelopes and an unrestricted grant, which will be used to cover pharmacodynamic and viral (HCV) monitoring, which are not included in this report." Comment: Study is industry sponsored
Free of early stopping?	Low risk	Comment: Study not stopped early
Free of baseline imbalance?	High risk	Quote from the publication: "Technical variants were not taken into account when randomizing the patients because in our center, results of elective living LT and split LT are similar to those obtained after whole LT. The need for artificial organ support also was not considered for randomization, as the placebo group would have a lower degree of IS anyway. The randomization was also independent of the presence of positive lymphocytotoxic cross‐match and of viral HBV or HCV infection. The characteristics of the study population are summarized in Table 1. The groups differed significantly in relation to total ischemia time, frequency of living donor LT, need for artificial (renal, hepatic, and pulmonary) organ support, and mean creatinine values during the first 14 post‐LT days." Comment: Study not free from baseline imbalance