title: De novo sirolimus-based immunosuppression after liver transplantation for hepatocellular carcinoma: long-term outcomes and side effects.
abstract: BACKGROUND
  We report long-term outcomes and side effects after transplantation for hepatocellular carcinoma (HCC) using de novo, sirolimus-based immunosuppression (IS).
  
  
  METHODS
  A total of 70 patients with HCC (mean age: 54.4+/-7 years, female/male: 12/58) were transplanted and included in the study. Immunosuppression included de novo sirolimus, low-dose calcineurin inhibitor for 6 to 12 months, with short-course (3 months) or no steroids.
  
  
  RESULTS
  After 49 months-median follow-up, eight patients have experienced an HCC recurrence, 2 of 34 when Milan criteria were respected (6%) and 6 of 36 when beyond Milan criteria (17%). One- and 4-year tumor-free survivals were 85 and 73%, when Milan criteria were respected and 82% and 75% when they were not, respectively. (P=0.9). After recurrence, mean survival was 23+/-28 months. Half (35 of 70) of the patients experienced a rejection. Incisional hernia (24 of 70, 34%), wound infection (12 of 70, 17%), anemia (39 of 70, 56%), leucopenia (39 of 70, 56%), high triglyceride (43 of 70, 61%), and cholesterol (28 of 70, 40%) levels and mouth ulcers (20 of 70, 29%) were among the most frequent complications. No hepatic artery thrombosis was observed.
  
  
  CONCLUSIONS
  These data suggest that de novo sirolimus-based immunosuppression is associated with satisfactory outcomes after transplantation, even in selected patients beyond Milan criteria. The protocol has proven safe, with an acceptable side-effect profile. This study supports the conduct of larger randomized trials investigating sirolimus after transplantation for HCC.
authors.affiliation: Department of Surgery, Section of Hepatobiliary, Pancreatic and Transplant Surgery, University of Alberta, Edmonton, Canada.
authors.forename: Christian
authors.initials: C
authors.lastname: Toso
authors.forename: Glenda A
authors.initials: GA
authors.lastname: Meeberg
authors.forename: David L
authors.initials: DL
authors.lastname: Bigam
authors.forename: Jose
authors.initials: J
authors.lastname: Oberholzer
authors.forename: A M James
authors.initials: AM
authors.lastname: Shapiro
authors.forename: Klaus
authors.initials: K
authors.lastname: Gutfreund
authors.forename: Mang M
authors.initials: MM
authors.lastname: Ma
authors.forename: Andrew L
authors.initials: AL
authors.lastname: Mason
authors.forename: Winnie W S
authors.initials: WW
authors.lastname: Wong
authors.forename: Vincent G
authors.initials: VG
authors.lastname: Bain
authors.forename: Norman M
authors.initials: NM
authors.lastname: Kneteman
mesh_terms: D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000601:surgery*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006084:Graft Rejection; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008113:Liver Neoplasms / Q000601:surgery*; D016031:Liver Transplantation / Q000009:adverse effects; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D018579:Patient Selection; D010865:Pilot Projects; D020123:Sirolimus / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D007166:Immunosuppressive Agents; D020123:Sirolimus