In renal transplantation, large randomized trials have shown that both IL-2Ra reduce the incidence Temsirolimus purchase of acute rejection and have a relatively good toxicity and safety profile.5,

6 But there have also been some concerns about the long-term effects, especially regarding posttransplant lymphoproliferative disorders (PTLD) and other malignancies.3 The effects of IL-2Ra have also been evaluated in a meta-analysis of kidney transplant recipients.7 The results showed that induction with IL-2Ra significantly reduces the risk of acute rejection but has no effect on graft or patient survival. A first nonsystematic review of the literature showed that in liver transplant patients, IL-2Ra are not only used in addition to standard immunosuppression but are mainly used to reduce other immunosuppressive drugs, such as calcineurin inhibitors (CNI) and corticosteroids, thereby possibly decreasing the

incidence and severity of their adverse effects. We have therefore structured this meta-analysis into three separate comparisons as follows: (1) comparison of IL-2Ra versus placebo or no treatment; (2) comparison of IL-2Ra with reduced and/or delayed CNI versus placebo or no IL-2Ra treatment in combination with standard immunosuppression; and (3) comparison of IL-2Ra and reduced or no corticosteroids versus placebo or no IL-2Ra treatment in combination with standard immunosuppression. ACA, available-case-analysis; AE, adverse event; CMV, cytomegalovirus; INCB018424 mouse CNI, calcineurin inhibitor; eGFR, estimated glomerular filtration rate; GFR, glomerular filtration rate; HCV, hepatitis C virus; IL-2R, interleukin-2 receptor; IL-2Ra, interleukin-2 receptor antagonists; ITT, intention-to-treat analysis;

LOCF, last-observation-carried-forward; MD, mean difference; MDRD, modification of diet in renal disease; MMF, mycophenolate mofetil; NNT, number needed to treat; PTDM, post-transplant diabetes mellitus; PTLD, post-transplant lymphoproliferative disease; REML, restricted maximum likelihood; SAE, serious adverse event. The methods of literature search, the inclusion and exclusion criteria, outcome measures, and methods of statistical analysis were defined in a protocol according to the recommendations in the Cochrane Handbook for Systematic Reviews of Interventions.8 We also used the Preferred Items for Systematic Reviews and Meta-Analysis (PRISMA) and Meta-Analysis of Observational Studies in Epidemiology MycoClean Mycoplasma Removal Kit (MOOSE) recommendations for study reporting.9, 10 A systematic literature search was performed without language restrictions from inception to December 2010 in the following databases: Medline/PubMed, Embase, Transplant Library, and Cochrane Library. The keywords used were “liver transplantation,” “interleukin 2 receptor inhibitor/antagonist,” “basiliximab,” “daclizumab,” “simulect,” “zenapax,” and abbreviations thereof, combined with appropriate Boolean operators. The reference lists in all identified trials were examined for further relevant articles.