title: Indications and management of everolimus after liver transplantation.
abstract: OBJECTIVE
  Our aim was to assess our experience with the use and management of everolimus after orthotopic liver transplantation (OLT).
  
  
  METHODS
  Among the 759 patients who underwent transplantation from 1988 to 2008, 25 (3.2%) received immunosuppression with everolimus. Their mean age was 55.6 years. We analyzed indications for use, time between transplantation and introduction of everolimus, as well as its efficacy, side effects, and patient survival.
  
  
  RESULTS
  The indications for everolimus treatment were: extended hepatocellular carcinoma (HCC) in the explanted liver (n = 6; 24%); HCC recurrence during follow-up (n = 4; 16%); de novo tumor (n = 6; 24%); refractory rejection (n = 3; 12%); side effects of calcineurin inhibitors (CNI; n = 3; 12%); and other causes (n = 3; 12%). Mean time between OLT and everolimus treatment was 40 +/- 33 months (range, 10 days-178 months). Mean follow-up after conversion was 10 +/- 9 months (range, 1.5-25 months). More than half of the patients resolved the event for which the drug was indicated: 75% of patients with refractory rejection; 60% of those with renal insufficiency; and 100% of those converted for neurotoxicity or hepatotoxicity. Two patients with recurrent HCC and 1 with extended HCC died at a mean time of 10.5 months. The 6 cases of de novo tumors were operated and are healthy. Side effects were dyslipidemia in 8 and infection in 2. Five patients (20%) discontinued the drug.
  
  
  CONCLUSIONS
  In the early posttransplantation period, everolimus is indicated for refractory rejection or as prophylaxis for recurrence of extended tumors. In any time but especially in the late period, everolimus is indicated for patients with serious side effects due to a CNI or to a de novo tumor.
authors.affiliation: HBP Surgery and Transplant Department, Hospital Universitario Vall d'Hebron, Universidad Autónoma de Barcelona, Barcelona, Spain. ibilbao@vhebron.net
authors.forename: I
authors.initials: I
authors.lastname: Bilbao
authors.forename: G
authors.initials: G
authors.lastname: Sapisochin
authors.forename: C
authors.initials: C
authors.lastname: Dopazo
authors.forename: J L
authors.initials: JL
authors.lastname: Lazaro
authors.forename: L
authors.initials: L
authors.lastname: Pou
authors.forename: L
authors.initials: L
authors.lastname: Castells
authors.forename: M
authors.initials: M
authors.lastname: Caralt
authors.forename: L
authors.initials: L
authors.lastname: Blanco
authors.forename: A
authors.initials: A
authors.lastname: Gantxegi
authors.forename: C
authors.initials: C
authors.lastname: Margarit
authors.forename: R
authors.initials: R
authors.lastname: Charco
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D006528:Carcinoma, Hepatocellular / Q000601:surgery; D000068338:Everolimus; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D008104:Liver Cirrhosis, Alcoholic / Q000601:surgery; D016031:Liver Transplantation / Q000276:immunology* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000453:epidemiology; D012008:Recurrence; D012189:Retrospective Studies; D020123:Sirolimus / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016019:Survival Analysis; D017741:Survivors; D016559:Tacrolimus / Q000009:adverse effects / Q000627:therapeutic use; D013997:Time Factors
chemical_list: D007166:Immunosuppressive Agents; D000068338:Everolimus; D020123:Sirolimus; D016559:Tacrolimus