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.