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

Patel, Seema
Asthana, Sonal
Kawahara, Toshiyasu
Girgis, Safwat
Kneteman, Norman N.
Shapiro, A M James
Bigam, David L.
Published in Clinical Transplantation. 2010, vol. 24, no. 5, p. 695-700
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.
Keywords AdolescentAdultAgedCells, CulturedFemaleGraft Rejection/*drug therapyHepatocytes/*cytology/*drug effectsHumansImmunosuppressive Agents/*therapeutic useLiver Regeneration/drug effects*Liver Transplantation*Living DonorsMaleMiddle AgedProspective StudiesRetrospective StudiesSirolimus/*therapeutic useTreatment OutcomeYoung Adult
PMID: 20002466
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Research group Transplantation et hépatologie (905)
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TOSO, Christian et al. The impact of sirolimus on hepatocyte proliferation after living donor liver transplantation. In: Clinical Transplantation, 2010, vol. 24, n° 5, p. 695-700. https://archive-ouverte.unige.ch/unige:21346

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Deposited on : 2012-05-23

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