The impact of sirolimus on hepatocyte proliferation after living donor liver transplantation

Clin Transplant. 2010 Sep-Oct;24(5):695-700. doi: 10.1111/j.1399-0012.2009.01159.x.

Abstract

Background: There is a lack of data on the use of sirolimus after partial liver transplantation, especially regarding its impact on post-transplant regeneration.

Methods: We reviewed adult living donor transplantations, with de novo sirolimus (n = 7) and without sirolimus (n = 21). Liver biopsies were stained for KI-67, a proliferation marker. Controls included specimens with normal liver parenchyma (n = 13).

Results: Both groups had similar demographics, graft and patient survival and complication rates. During the first six wk and over the whole first year post-transplant, the use of sirolimus was associated with lower levels of hepatocyte proliferation compared to sirolimus-free patients, (overall, 0.3 [0-7.2] vs. 3 [0-49] KI-67 positive hepatocytes per high power field, p ≤ 0.05). The levels observed in the sirolimus group were similar to those seen in non-transplanted control patients with normal parenchyma (0.2 [0-1.3], p = NS). Post-transplant hepatocyte proliferation correlated with the serum levels of sirolimus (p ≤ 0.05), but not with those of tacrolimus or with the dose of mycophenolate mofetil (p = 0.9 and 0.3, respectively).

Conclusions: These data suggest that sirolimus is associated with decreased post-transplant hepatocyte proliferation. The clinical significance of this observation remains to be fully determined.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Cells, Cultured
  • Female
  • Graft Rejection / drug therapy*
  • Hepatocytes / cytology*
  • Hepatocytes / drug effects*
  • Humans
  • Immunosuppressive Agents / therapeutic use*
  • Liver Regeneration / drug effects
  • Liver Transplantation*
  • Living Donors*
  • Male
  • Middle Aged
  • Prospective Studies
  • Retrospective Studies
  • Sirolimus / therapeutic use*
  • Treatment Outcome
  • Young Adult

Substances

  • Immunosuppressive Agents
  • Sirolimus