title: Use of Everolimus in Liver Transplantation: Recommendations From a Working Group.
abstract: 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.
authors: 1 Hepatobiliary Surgery and Liver Transplantation Unit, University of Pisa Medical School Hospital, Pisa, Italy. 2 Gastroenterology and Transplant Hepatology, Ospedale Papa Giovanni XXIII, Bergamo, Italy. 3 Department of Medical and Surgical Sciences, University of Bologna and Azienda Ospedaliero-Universitaria di Bologna, Policlinico Sant'Orsola Malpighi, Bologna, Italy. 4 Department of General Surgery and Transplantation, Niguarda Hospital, Milan, Italy. 5 Department of Experimental Medicine and Surgery, Transplantation Surgery, Rome, Italy. 6 Mediterranean Institute for Transplantation and Advanced Specialized Therapies (ISMETT/IRCCS), Palermo, Italy. 7 University Hospital of Padua, Padua, Italy.
authors: Paolo
authors: P
authors: De Simone
authors: Stefano
authors: S
authors: Fagiuoli
authors: Matteo
authors: M
authors: Cescon
authors: Luciano
authors: L
authors: De Carlis
authors: Giuseppe
authors: G
authors: Tisone
authors: Riccardo
authors: R
authors: Volpes
authors: Umberto
authors: U
authors: Cillo
mesh_terms: D032921:Consensus; D003299:Cooperative Behavior; D003697:Delphi Technique; D000068338:Everolimus / Q000009:adverse effects / Q000627:therapeutic use*; D006084:Graft Rejection / Q000201:enzymology / Q000276:immunology / Q000517:prevention & control*; D006085:Graft Survival / Q000187:drug effects*; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D033183:Interdisciplinary Communication; D016031:Liver Transplantation / Q000009:adverse effects*; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D015398:Signal Transduction / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D007166:Immunosuppressive Agents; D047428:Protein Kinase Inhibitors; D000068338:Everolimus; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases