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

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.