Conversion to sirolimus immunosuppression in liver transplantation recipients with hepatocellular carcinoma: Report of an initial experience.
OBJECTIVE
To report a retrospective analysis of preliminary results of 36 patients who received sirolimus (SRL, Rapamune, rapamycin) in a consecutive cohort of 248 liver allograft recipients.


METHODS
Thirty-six liver transplant patients with hepatocellular carcinoma (HCC) who were switched to SRL-based immunosuppression therapy from tacrolimus were enrolled in this study. The patients who were diagnosed as advanced HCC before orthotopic liver transplantation (OLT) were divided into group A (n = 11), those who were found to have HCC recurrence and/or metastasis after OLT were assigned to group B (n = 18), and those who developed renal insufficiency caused by calcineurin inhibitor (CNI) were assigned to group C (n = 7) after OLT.


RESULTS
The patients were followed up for a median of 10.4 mo (range, 3.8-19.1 mo) after conversion to SRL therapy and 12.3 mo (range, 5.1-34.4 mo) after OLT. Three patients developed mild acute cellular rejection 2 wk after initiating SRL therapy, which was fully reversed after prednisolone pulse therapy. In group A, only 1 patient was found to have HCC recurrence and metastasis 12 mo after OLT. In group B, 66.7% (12/18) patients (2 with progressive tumor, 7 with stable tumor and 3 without tumor) were still alive due to conversing to SRL and/or resection for HCC recurrence at the end of a median follow-up of 6.8 mo post conversion and 10.7 mo posttransplant. In group C, no HCC recurrence was demonstrated in 7 patients, and renal function became normal after SRL therapy. Thrombocytopenia (n = 2), anemia (n = 8), and oral aphthous ulcers (n = 7) found in our cohort were easily manageable.


CONCLUSIONS
The conversion to SRL-based immunosuppression may inhibit the recurrence and metastasis of HCC and improve CNI-induced renal insufficiency in OLT patients with HCC.
Zhou
Jian
J
Liver Cancer Institute and Zhongshan Hospital, Fudan University, Shanghai 200032, China. jianzhou@zshospital.net
Fan
Jia
J
Wang
Zheng
Z
Wu
Zhi-Quan
ZQ
Qiu
Shuang-Jian
SJ
Huang
Xiao-Wu
XW
Yu
Yao
Y
Sun
Jian
J
Xiao
Yong-Sheng
YS
He
Yi-Feng
YF
Wang
Yu-Qi
YQ
Tang
Zhao-You
ZY
D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D019703:Calcineurin / Q000009:adverse effects; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000601:surgery*; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D015994:Incidence; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000601:surgery*; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000188:drug therapy / Q000517:prevention & control; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000517:prevention & control; D010750:Phosphoproteins / Q000009:adverse effects; D051437:Renal Insufficiency / Q000139:chemically induced / Q000188:drug therapy; D012189:Retrospective Studies; D020123:Sirolimus / Q000627:therapeutic use*; D016559:Tacrolimus / Q000627:therapeutic use; D014180:Transplantation; D014184:Transplantation, Homologous
D048868:Adaptor Proteins, Signal Transducing; C491861:CABIN1 protein, human; D007166:Immunosuppressive Agents; D010750:Phosphoproteins; D019703:Calcineurin; D020123:Sirolimus; D016559:Tacrolimus