术前应用免疫检查点抑制剂的肝癌肝移植受者预后分析：附12例报道_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

杜俊杰 ¹ , 魏臻煜 ² , 刘建勇 ¹ , 江艺 ¹ , 吕立志 ¹ ,  蔡秋程 ¹

1. ;
2. ;

Corresponding author：

蔡秋程, Email: cqcheng1122@163.com

Keywords：

免疫检查点抑制剂; 肝癌肝移植; 预后

DOI：

10.7507/1007-9424.202508127

Video：

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目的探讨术前应用免疫检查点抑制剂（immune checkpoint inhibitors，ICIs）的肝癌肝移植受者的预后情况。方法回顾性分析12例术前接受ICIs治疗的肝癌肝移植受者的临床资料，总结受者术后生存状态以及并发症发生情况。结果 12例受者术前应用ICIs治疗1～23个周期，从停药到肝移植的间隔时间为57～475 d。4例受者在术后2周内发生排斥反应，其中3例经糖皮质激素冲击治疗及调整他克莫司剂量后好转，1例因急性排斥反应死亡。1例受者于术后3周出现药物性肝损伤，经对症处理后好转，但后续发生胆管狭窄。1例患者于术后1年因肿瘤复发而死亡。结论 ICIs可用于肝癌肝移植术前治疗，但需警惕术后排斥反应的发生，对于远期胆管并发症的发生尚不明确，有待更多临床资料进一步验证。

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2.	Munker S, De Toni EN. Use of checkpoint inhibitors in liver transplant recipients. United European Gastroenterol J, 2018, 6(7): 970-973.
3.	Kumar V, Shinagare AB, Rennke HG, et al. The Safety and Efficacy of Checkpoint Inhibitors in Transplant Recipients: A Case Series and Systematic Review of Literature. Oncologist, 2020, 25(6): 505-514.
4.	Topalian SL, Taube JM, Pardoll DM. Neoadjuvant checkpoint blockade for cancer immunotherapy. Science, 2020, 367(6477): eaax0182.
5.	O'Donnell JS, Hoefsmit EP, Smyth MJ, et al. The Promise of Neoadjuvant Immunotherapy and Surgery for Cancer Treatment. Clin Cancer Res, 2019, 25(19): 5743-5751.
6.	刘召波, 武聚山, 林栋栋, 等. PD-1抑制剂用于肝癌肝移植术前治疗的安全性探讨. 器官移植, 2021, 12(4): 445-9.
7.	崔春晓, 杨柳晓, 王颖, 等. 肝癌患者肝移植术前使用PD-1抑制剂对移植后排斥反应的影响. 中国临床医学, 2020, 27(3): 444-7.
8.	Nordness MF, Hamel S, Godfrey CM, et al. Fatal hepatic necrosis after nivolumab as a bridge to liver transplant for HCC: Are checkpoint inhibitors safe for the pretransplant patient?. Am J Transplant, 2020, 20(3): 879-883.
9.	Slovak R, Ludwig JM, Gettinger SN, et al. Immuno-thermal ablations - boosting the anticancer immune response. J Immunother Cancer, 2017, 5(1): 78.
10.	Wang J, Wang J, Wang J, et al. Combination treatment for advanced hepatocellular carcinoma with portal vein tumour thrombus: A case report. J Int Med Res, 2021, 49(2): 300060521994406.
11.	Chiang CL, Chan ACY, Chiu KWH, et al. Combined Stereotactic Body Radiotherapy and Checkpoint Inhibition in Unresectable Hepatocellular Carcinoma: A Potential Synergistic Treatment Strategy. Front Oncol, 2019 Nov 12: 9: 1157.
12.	宾阳阳, 李杰群, 李强, 等. PD-1单克隆抗体治疗实体器官移植术后恶性肿瘤的系统评价. 器官移植, 2020, 11(3): 384-90.
13.	Morita M, Fujino M, Jiang G, et al. PD-1/B7-H1 interaction contribute to the spontaneous acceptance of mouse liver allograft. Am J Transplant, 2010, 10(1): 40-46.
14.	Riella LV, Paterson AM, Sharpe AH, et al. Role of the PD-1 pathway in the immune response. Am J Transplant, 2012, 12(10): 2575-2587.
15.	Ono Y, Perez-Gutierrez A, Nakao T, et al. Graft-infiltrating PD-L1hi cross-dressed dendritic cells regulate antidonor T cell responses in mouse liver transplant tolerance. Hepatology, 2018, 67(4): 1499-1515.
16.	Riella LV, Watanabe T, Sage PT, et al. Essential role of PDL1 expression on nonhematopoietic donor cells in acquired tolerance to vascularized cardiac allografts. Am J Transplant, 2011, 11(4): 832-840.
17.	师珏珏, 徐钧, 张海燕, et al. 系统评价巴利昔单抗诱导的无激素免疫抑制方案在肝移植中的有效性. 实用器官移植电子杂志, 2022, 10(4): 326-331.
18.	Koga N, Suzuki J, Kosuge H, et al. Blockade of the interaction between PD-1 and PD-L1 accelerates graft arterial disease in cardiac allografts. Arterioscler Thromb Vasc Biol, 2004, 24(11): 2057-2062.
19.	Mazzaferro V, Llovet JM, Miceli R, et al. Predicting survival after liver transplantation in patients with hepatocellular carcinoma beyond the Milan criteria: a retrospective, exploratory analysis. Lancet Oncol, 2009, 10(1): 35-43.
20.	Welker MW, Bechstein WO, Zeuzem S, et al. Recurrent hepatocellular carcinoma after liver transplantation - an emerging clinical challenge. Transpl Int, 2013, 26(2): 109-118.
21.	Fernandez-Sevilla E, Allard MA, Selten J, et al. Recurrence of hepatocellular carcinoma after liver transplantation: Is there a place for resection?. Liver Transpl, 2017, 23(4): 440-447.
22.	Goldaracena N, Gorgen A, Doyle A, et al. Live donor liver transplantation for patients with hepatocellular carcinoma offers increased survival vs. deceased donation. J Hepatol, 2019, 70(4): 666-673.
23.	d'Izarny-Gargas T, Durrbach A, Zaidan M. Efficacy and tolerance of immune checkpoint inhibitors in transplant patients with cancer: A systematic review. Am J Transplant, 2020, 20(9): 2457-2465.

1. Kim CG, Kim C, Yoon SE, et al. Hyperprogressive disease during PD-1 blockade in patients with advanced hepatocellular carcinoma. J Hepatol, 2021, 74(2): 350-359.
2. Munker S, De Toni EN. Use of checkpoint inhibitors in liver transplant recipients. United European Gastroenterol J, 2018, 6(7): 970-973.
3. Kumar V, Shinagare AB, Rennke HG, et al. The Safety and Efficacy of Checkpoint Inhibitors in Transplant Recipients: A Case Series and Systematic Review of Literature. Oncologist, 2020, 25(6): 505-514.
4. Topalian SL, Taube JM, Pardoll DM. Neoadjuvant checkpoint blockade for cancer immunotherapy. Science, 2020, 367(6477): eaax0182.
5. O'Donnell JS, Hoefsmit EP, Smyth MJ, et al. The Promise of Neoadjuvant Immunotherapy and Surgery for Cancer Treatment. Clin Cancer Res, 2019, 25(19): 5743-5751.
6. 刘召波, 武聚山, 林栋栋, 等. PD-1抑制剂用于肝癌肝移植术前治疗的安全性探讨. 器官移植, 2021, 12(4): 445-9.
7. 崔春晓, 杨柳晓, 王颖, 等. 肝癌患者肝移植术前使用PD-1抑制剂对移植后排斥反应的影响. 中国临床医学, 2020, 27(3): 444-7.
8. Nordness MF, Hamel S, Godfrey CM, et al. Fatal hepatic necrosis after nivolumab as a bridge to liver transplant for HCC: Are checkpoint inhibitors safe for the pretransplant patient?. Am J Transplant, 2020, 20(3): 879-883.
9. Slovak R, Ludwig JM, Gettinger SN, et al. Immuno-thermal ablations - boosting the anticancer immune response. J Immunother Cancer, 2017, 5(1): 78.
10. Wang J, Wang J, Wang J, et al. Combination treatment for advanced hepatocellular carcinoma with portal vein tumour thrombus: A case report. J Int Med Res, 2021, 49(2): 300060521994406.
11. Chiang CL, Chan ACY, Chiu KWH, et al. Combined Stereotactic Body Radiotherapy and Checkpoint Inhibition in Unresectable Hepatocellular Carcinoma: A Potential Synergistic Treatment Strategy. Front Oncol, 2019 Nov 12: 9: 1157.
12. 宾阳阳, 李杰群, 李强, 等. PD-1单克隆抗体治疗实体器官移植术后恶性肿瘤的系统评价. 器官移植, 2020, 11(3): 384-90.
13. Morita M, Fujino M, Jiang G, et al. PD-1/B7-H1 interaction contribute to the spontaneous acceptance of mouse liver allograft. Am J Transplant, 2010, 10(1): 40-46.
14. Riella LV, Paterson AM, Sharpe AH, et al. Role of the PD-1 pathway in the immune response. Am J Transplant, 2012, 12(10): 2575-2587.
15. Ono Y, Perez-Gutierrez A, Nakao T, et al. Graft-infiltrating PD-L1hi cross-dressed dendritic cells regulate antidonor T cell responses in mouse liver transplant tolerance. Hepatology, 2018, 67(4): 1499-1515.
16. Riella LV, Watanabe T, Sage PT, et al. Essential role of PDL1 expression on nonhematopoietic donor cells in acquired tolerance to vascularized cardiac allografts. Am J Transplant, 2011, 11(4): 832-840.
17. 师珏珏, 徐钧, 张海燕, et al. 系统评价巴利昔单抗诱导的无激素免疫抑制方案在肝移植中的有效性. 实用器官移植电子杂志, 2022, 10(4): 326-331.
18. Koga N, Suzuki J, Kosuge H, et al. Blockade of the interaction between PD-1 and PD-L1 accelerates graft arterial disease in cardiac allografts. Arterioscler Thromb Vasc Biol, 2004, 24(11): 2057-2062.
19. Mazzaferro V, Llovet JM, Miceli R, et al. Predicting survival after liver transplantation in patients with hepatocellular carcinoma beyond the Milan criteria: a retrospective, exploratory analysis. Lancet Oncol, 2009, 10(1): 35-43.
20. Welker MW, Bechstein WO, Zeuzem S, et al. Recurrent hepatocellular carcinoma after liver transplantation - an emerging clinical challenge. Transpl Int, 2013, 26(2): 109-118.
21. Fernandez-Sevilla E, Allard MA, Selten J, et al. Recurrence of hepatocellular carcinoma after liver transplantation: Is there a place for resection?. Liver Transpl, 2017, 23(4): 440-447.
22. Goldaracena N, Gorgen A, Doyle A, et al. Live donor liver transplantation for patients with hepatocellular carcinoma offers increased survival vs. deceased donation. J Hepatol, 2019, 70(4): 666-673.
23. d'Izarny-Gargas T, Durrbach A, Zaidan M. Efficacy and tolerance of immune checkpoint inhibitors in transplant patients with cancer: A systematic review. Am J Transplant, 2020, 20(9): 2457-2465.

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