PT  - JOURNAL ARTICLE
AU  - Bzeizi Khalid
AU  - Smith Richard
AU  - Benmousa Ali
AU  - Dama Madhukar M.V.SC
AU  - Aba-Alkhail Faisal
AU  - Jalan Rajiv
AU  - Broering Dieter
TI  - Long term outcomes of Everolimus therapy in <em>de novo</em> liver transplantation: a systematic review and meta-analysis of randomized controlled trials
AID  - 10.1101/703215
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 703215
4099  - http://biorxiv.org/content/early/2019/07/15/703215.short
4100  - http://biorxiv.org/content/early/2019/07/15/703215.full
AB  - Background Risk of nephrotoxicity in liver transplant patients on calcineurin inhibitors (CnIs) is a concern. Several controlled trials reported benefit of Everolimus (EVR) in minimizing this risk when combined with a reduced CnIs dose.Objective To systematically review the efficacy and safety of EVR, alone or with reduced CnI dose, as compared to CnI alone post liver transplantation.Methods We searched MEDLINE, Scopus and the Cochrane Library for randomized controlled trials (RCTs) comparing EVR and CnI based regimens post liver transplanation. Assessment of studies and data extraction was undertaken independently.Results Eight studies were selected describing 769 patients. Cockcroft-Gault GFR (CG-GFR) was significantly higher at one (p=0.05), 3 & 5 years (p=0.030) in patients receiving EVR as compared to those receiving CnI therapy. The composite end point of efficacy failure was similar between the two arms after 1, 3 & 5 years of study. Higher number of patients discontinued EVR due to adverse effects in one year, however no difference was noted after 3 & 5 years. A higher rates of proteinuria, peripheral edema and incisional hernia were noted in patients on EVR.Conclusion The analysis confirms non-inferiority of EVR and reduced CnI combination. Patients on the combination regimen had better renal function compared to standard CnI therapy.