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

• Published in: Clinical transplantation 2010-09, Vol.24 (5), p.695-700
• Main Authors: Toso, Christian, Patel, Seema, Asthana, Sonal, Kawahara, Toshiyasu, Girgis, Safwat, Kneteman, Norman N., Shapiro, A.M. James, Bigam, David L.
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Aged; Antibacterial agents; Antibiotics. Antiinfectious agents. Antiparasitic agents; Biological and medical sciences; Cells, Cultured; donor; Female; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Graft Rejection - drug therapy; hepatocyte; Hepatocytes - cytology; Hepatocytes - drug effects; Humans; Immunosuppressive Agents - therapeutic use; live; liver; Liver Regeneration - drug effects; Liver Transplantation; Liver, biliary tract, pancreas, portal circulation, spleen; Living Donors; Male; Medical sciences; Middle Aged; Pharmacology. Drug treatments; proliferation; Prospective Studies; regeneration; Retrospective Studies; sirolimus; Sirolimus - therapeutic use; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases; Surgery of the digestive system; Tissue, organ and graft immunology; Treatment Outcome; Young Adult
• ISSN: 0902-0063; 1399-0012
• DOI: 10.1111/j.1399-0012.2009.01159.x

Toso C, Patel S, Asthana S, Kawahara T, Girgis S, Kneteman NN, Shapiro AMJ, Bigam DL. The impact of sirolimus on hepatocyte proliferation after living donor liver transplantation.
Clin Transplant 2009 DOI: 10.1111/j.1399‐0012.2009.01159.x
© 2009 John Wiley & Sons A/S. : 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.