title: Everolimus in de novo liver transplant recipients: a systematic review.
abstract: BACKGROUND
  Everolimus has no nephrotoxicity and is used to treat patients with post-liver transplant chronic renal insufficiency. The present systematic review was to evaluate the efficacy and safety of everolimus in de novo liver transplant patients.
  
  
  METHODS
  Randomized controlled trials comparing everolimus for de novo liver transplant in PubMed, the Cochrane Library, and ScienceDirect published up to March 31, 2014 were searched by two independent reviewers. Mean differences and 95% confidence interval (95% CI) for renal function, relative risk (RR) and 95% CI for treated biopsy-proven acute rejection (tBPAR), graft loss, death, neoplasms/tumor recurrence, and adverse events were collected. Meta-analyses were performed with RevMan version 5.10.
  
  
  RESULTS
  A total of four randomized controlled trials covering 1119 cases were included. The meta-analyses revealed that compared with standard exposure of calcineurin inhibitors (CNIs), everolimus combined with reduced CNIs improved creatinine clearance (calculated with the Cockcroft-Gault formula) by 5.13 mL/min at one year (95% CI: 0.42-9.84; P=0.03), and decreased tBPAR (RR: 0.56; 95% CI: 0.35-0.90; P=0.02). Everolimus initiation with CNIs elimination improved glomerular filtration rate (GFR, measured with the modification of diet in renal disease formula) of 10.42 mL/min/1.73 m2 (95% CI: 3.44-17.41; P<0.01) one year after treatment, but increased tBPAR (RR: 1.71; 95% CI: 1.15-2.53; P<0.01). Everolimus decreased the risk of neoplasms/tumor recurrence after liver transplant (RR: 0.60; 95% CI: 0.34-1.03; P=0.06), but was associated with greater risk of adverse events which resulted in drug discontinuation (RR: 1.98; 95% CI: 1.49-2.64; P<0.01).
  
  
  CONCLUSIONS
  Early introduction of everolimus combined with low-dose or no CNI in de novo liver transplant significantly improves renal function one year post treatment. Everolimus combined with low-dose CNI decreases the risk of tBPAR one year after liver transplant, but everolimus administered without CNIs increases tBPAR.
authors.affiliation: Department of Hepatobiliary Surgery, First Affiliated Hospital of Chongqing Medical University, Chongqing 404100, China. wzjtcy@126.com.
authors.forename: Cheng-Yong
authors.initials: CY
authors.lastname: Tang
authors.forename: Ai
authors.initials: A
authors.lastname: Shen
authors.forename: Xu-Fu
authors.initials: XF
authors.lastname: Wei
authors.forename: Qing-Dong
authors.initials: QD
authors.lastname: Li
authors.forename: Rui
authors.initials: R
authors.lastname: Liu
authors.forename: He-Jun
authors.initials: HJ
authors.lastname: Deng
authors.forename: Yong-Zhong
authors.initials: YZ
authors.lastname: Wu
authors.forename: Zhong-Jun
authors.initials: ZJ
authors.lastname: Wu
mesh_terms: D065095:Calcineurin Inhibitors / Q000008:administration & dosage; D004359:Drug Therapy, Combination; D000068338:Everolimus / Q000009:adverse effects / Q000627:therapeutic use*; D006084:Graft Rejection / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D008113:Liver Neoplasms / Q000517:prevention & control*; D016031:Liver Transplantation; D009364:Neoplasm Recurrence, Local / Q000517:prevention & control*; D016032:Randomized Controlled Trials as Topic; D051436:Renal Insufficiency, Chronic / Q000503:physiopathology*
chemical_list: D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D000068338:Everolimus