title: Use of everolimus in liver transplantation: The French experience.
abstract: The mammalian target of rapamycin (mTOR) inhibitor everolimus is approved for rejection prophylaxis after liver transplantation. The current article pools the experience of French liver transplant surgeons and physicians in use of everolimus and, particularly, practical guidance on dosing, appropriate concomitant immunosuppression and management of adverse events. In terms of indication, introduction of everolimus from week 4 after liver transplantation, with or without concomitant calcineurin inhibitor (CNI) therapy, offers a significant renal benefit without loss of immunosuppressive efficacy. De novo treatment with everolimus, either selectively or systematically, may play a role in the prevention and treatment of recurrence of hepatocellular cancer and de novo malignancies. For maintenance patients, the most frequent indications for introducing everolimus are in response to renal dysfunction, recurrent hepatocellular cancer, diabetes, hypertension, or neurotoxicity, or as a preventative approach to avoid malignancies. Of these, the strongest evidence exists for a renoprotective effect. However, the low rate of acute rejection following switch of maintenance patients from CNI-based to everolimus-based therapy means that this can be considered even where robust data are not yet available. Most adverse events associated with mTOR inhibitors can usually be managed successfully, often with concentration-controlled dose reductions. Dosing algorithms are provided, with suggestions for target ranges in specific settings, and treatment strategies for the most common side effects are proposed. Although further research is required, everolimus has become an established part of the immunosuppressive arsenal for liver transplant recipients over the last decade. Sharing experience from units which have embraced its use may help other centers develop their own protocols.
authors.affiliation: Unité de Transplantation Hépatique-Fédération des Spécialités Digestives, Hôpital Edouard Herriot and Université Claude Bernard Lyon 1, Lyon, France.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Dumortier
authors.affiliation: Service des Maladies de l'Appareil Digestif et de la Nutrition, Hôpital Claude Huriez Centre Hospitalier Universitaire, Lille, France.
authors.forename: Sebastien
authors.initials: S
authors.lastname: Dharancy
authors.affiliation: Unité Médicale de Transplantation Hépatique, AP-HP Hôpital Universitaire Pitié Salpêtrière, Paris, France.
authors.forename: Yvon
authors.initials: Y
authors.lastname: Calmus
authors.affiliation: Service d'Hépato-Gastroenterologie, Hôpital Henri Mondor, Assistance Publique, Hôpitaux de Paris, Créteil, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Duvoux
authors.affiliation: Hepatology and Liver Intensive Care, INSERM U1149, Hospital Beaujon, Clichy, France.
authors.forename: François
authors.initials: F
authors.lastname: Durand
authors.affiliation: Chirurgie Digestive, Endocrinienne et Transplantation Hépatique, Hôpital Trousseau, Tours, France.
authors.forename: Ephrem
authors.initials: E
authors.lastname: Salamé
authors.affiliation: AP-HP Hôpital Paul-Brousse Centre Hépato-Biliaire and INSERM, Unité 1193, Université Paris-Sud, UMR S1193, Villejuif, France. Electronic address: faouzi.saliba@pbr.aphp.fr.
authors.forename: Faouzi
authors.initials: F
authors.lastname: Saliba
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000601:surgery*; D000068338:Everolimus / Q000627:therapeutic use*; D005602:France; D006084:Graft Rejection; D006801:Humans; D007166:Immunosuppressive Agents; D008113:Liver Neoplasms / Q000601:surgery*; D016031:Liver Transplantation; D009364:Neoplasm Recurrence, Local; D020123:Sirolimus
chemical_list: D007166:Immunosuppressive Agents; D000068338:Everolimus; D020123:Sirolimus