Long term outcomes of Everolimus therapy in de novo liver transplantation: a systematic review and meta-analysis of randomized controlled trials

BackgroundRisk 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.\n\nObjectiveTo systematically review the efficacy and safety of EVR, alone or with reduced CnI dose, as compared to CnI alone post liver transplantation.\n\nMethodsWe 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.\n\nResultsEight 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.\n\nConclusionThe analysis confirms non-inferiority of EVR and reduced CnI combination. Patients on the combination regimen had better renal function compared to standard CnI therapy.