title: Conversion From Calcineurin to Mammalian Target of Rapamycin Inhibitors in Liver Transplantation: A Meta-Analysis of Randomized Controlled Trials.
abstract: BACKGROUND
  Conversion to mammalian target of rapamycin inhibitors (mTORi) is often used in liver transplantation to overcome calcineurin inhibitor (CNI) nephrotoxicity but the evidence base for this approach is not well defined. To summarize the evidence, from randomized clinical trials (RCTs), for conversion from CNI to mTORi-based immunosuppression after liver transplantation.
  
  
  METHODS
  Databases and conference abstracts were searched up to August 2015. The RCTs evaluating conversion from CNI to mTORi-based maintenance immunosuppression after adult liver transplantation. Descriptive and quantitative information was extracted; summary mean difference and risk ratio (RR) estimates were synthesized under a random-effects model. Heterogeneity was assessed using the Q statistic and I.
  
  
  RESULTS
  Ten RCTs, with a total of 1927 patients, met the final inclusion criteria. Patients converted to mTORi had significantly better renal function at 1 year after randomization compared with patients remaining on CNI (mean difference, 7.48 mL/min per 1.73 m; 95% confidence interval [95% CI], 3.18-11.8). The risks of graft loss (RR, 0.77; 95% CI, 0.29-2.09; I, 31%) and patient death (RR, 1.05; 95% CI, 0.63-1.73; I, 0%) were similar for patients converted to mTORi and patients remaining on CNI. However, conversion to mTORi was associated with a higher risk of acute rejection (RR, 1.76; 95% CI, 1.33-2.34; I, 0%) and study discontinuation due to adverse events (RR, 2.17; 95% CI, 1.38-3.44; I, 63%) up to 1 year after randomization.
  
  
  CONCLUSIONS
  Conversion from CNI to mTORi after liver transplantation is associated with improved renal function after 1 year but increases the risk of acute rejection and may be poorly tolerated.
authors.affiliation: 1 Department of Surgery, University of Cambridge and NIHR Cambridge Biomedical Research Centre, Cambridge, United Kingdom. 2 Evidence-Based Medicine Unit, Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece. 3 Center for Evidence-Based Medicine, Department of Health Services, Policy and Practice, School of Public Health, Brown University, RI.
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Glover
authors.forename: Christopher J E
authors.initials: CJ
authors.lastname: Watson
authors.forename: Paul
authors.initials: P
authors.lastname: Gibbs
authors.forename: J Andrew
authors.initials: JA
authors.lastname: Bradley
authors.forename: Evangelia E
authors.initials: EE
authors.lastname: Ntzani
authors.forename: Vasilis
authors.initials: V
authors.lastname: Kosmoliaptsis
mesh_terms: D065095:Calcineurin Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D016009:Chi-Square Distribution; D057915:Drug Substitution; D006084:Graft Rejection / Q000276:immunology / Q000401:mortality / Q000517:prevention & control*; D006085:Graft Survival / Q000187:drug effects*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000009:adverse effects; D007668:Kidney / Q000187:drug effects / Q000503:physiopathology; D016031:Liver Transplantation / Q000009:adverse effects / Q000401:mortality; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D018570:Risk Assessment; D012307:Risk Factors; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D047428:Protein Kinase Inhibitors; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases