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.
Toso
Christian
C
Department of Surgery, Section of Hepatobiliary, Pancreatic and Transplant Surgery, University of Alberta Hospital, Edmonton, AB, Canada. christian.toso@hcuge.ch
Patel
Seema
S
Asthana
Sonal
S
Kawahara
Toshiyasu
T
Girgis
Safwat
S
Kneteman
Norman N
NN
Shapiro
A M James
AM
Bigam
David L
DL
D000293:Adolescent; D000328:Adult; D000368:Aged; D002478:Cells, Cultured; D005260:Female; D006084:Graft Rejection / Q000188:drug therapy*; D022781:Hepatocytes / Q000166:cytology* / Q000187:drug effects*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008115:Liver Regeneration / Q000187:drug effects; D016031:Liver Transplantation; D019520:Living Donors; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012189:Retrospective Studies; D020123:Sirolimus / Q000627:therapeutic use*; D016896:Treatment Outcome; D055815:Young Adult
D007166:Immunosuppressive Agents; D020123:Sirolimus