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

Transplantation. 2017 Feb;101(2):239-251. doi: 10.1097/TP.0000000000001438.


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, mammalian target of rapamycin inhibitors have received considerable attention as immunosuppressants because they are associated with a more favorable renal profile versus CNI, as well as antiproliferative activity in clinical studies. Comprehensive guidelines on use of everolimus (EVR) in LT are still lacking. In Italy, a project, named 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) antiproliferative effects of EVR; and (D) management of EVR-related 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.

Publication types

  • Consensus Development Conference
  • Practice Guideline
  • Review

MeSH terms

  • Consensus
  • Cooperative Behavior
  • Delphi Technique
  • Everolimus / adverse effects
  • Everolimus / therapeutic use*
  • Graft Rejection / enzymology
  • Graft Rejection / immunology
  • Graft Rejection / prevention & control*
  • Graft Survival / drug effects*
  • Humans
  • Immunosuppressive Agents / adverse effects
  • Immunosuppressive Agents / therapeutic use*
  • Interdisciplinary Communication
  • Liver Transplantation / adverse effects*
  • Protein Kinase Inhibitors / adverse effects
  • Protein Kinase Inhibitors / therapeutic use*
  • Signal Transduction / drug effects
  • TOR Serine-Threonine Kinases / antagonists & inhibitors*
  • TOR Serine-Threonine Kinases / metabolism
  • Time Factors
  • Treatment Outcome


  • Immunosuppressive Agents
  • Protein Kinase Inhibitors
  • Everolimus
  • MTOR protein, human
  • TOR Serine-Threonine Kinases