De novo sirolimus-based immunosuppression after liver transplantation for hepatocellular carcinoma: long-term outcomes and side effects

Transplantation. 2007 May 15;83(9):1162-8. doi: 10.1097/01.tp.0000262607.95372.e0.

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.

MeSH terms

  • Adult
  • Aged
  • Carcinoma, Hepatocellular / surgery*
  • Dose-Response Relationship, Drug
  • Female
  • Graft Rejection
  • Humans
  • Immunosuppressive Agents / administration & dosage
  • Immunosuppressive Agents / adverse effects
  • Immunosuppressive Agents / therapeutic use*
  • Liver Neoplasms / surgery*
  • Liver Transplantation* / adverse effects
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local
  • Patient Selection
  • Pilot Projects
  • Sirolimus / administration & dosage
  • Sirolimus / adverse effects
  • Sirolimus / therapeutic use*
  • Survival Analysis
  • Treatment Outcome

Substances

  • Immunosuppressive Agents
  • Sirolimus