Use of Everolimus in Liver Transplantation: Recommendations From a Working Group

Immunosuppression after liver transplantation (LT) is presently based on use of calcineurin inhibitors (CNI), although they are associated with an increased incidence of renal dysfunction, cardiovascular complications, and de novo and recurrent malignancies. Over the past decade, mTOR inhibitors have received considerable attention as immunosuppressants as they are associated with a more favorable renal profile vs. CNI, as well as anti-proliferative activity in clinical studies. Comprehensive guidelines on use of everolimus (EVR) in LT are still lacking. In Italy, a project "Everolimus: the road to long-term functioning" was initiated to collect the experience on EVR after LT with the aim of providing guidance for transplant clinicians. Herein, recommendations by this national consensus group, based on Delphi methodology, are presented. Consensus was reached on 20 of the 23 statements proposed, and their level of evidence, grade of recommendation, and percent of agreement are reported. Statements are grouped into 4 areas: A) renal function; B) time of EVR introduction, CNI reduction and elimination, and risk for graft rejection; C) anti-proliferative effects of EVR; and D) EVR adverse events. The high level of consensus shows that there is good agreement on the routine use of EVR in predefined clinical scenarios, especially in light of posttransplant nephrotoxicity and other adverse events associated with long-term administration of CNIs.