術前應用免疫檢查點抑制劑的肝癌肝移植受者預后分析：附12例報道_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

杜俊杰 ¹ , 魏臻煜 ² , 劉建勇 ¹ , 江藝 ¹ , 呂立志 ¹ ,  蔡秋程 ¹

1. ;
2. ;

Corresponding?author：

蔡秋程, Email: cqcheng1122@163.com

Keywords：

免疫檢查點抑制劑; 肝癌肝移植; 受者；預后

DOI：

10.7507/1007-9424.202508127

Video：

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目的探討術前應用免疫檢查點抑制劑（immune checkpoint inhibitors，ICIs）的肝癌肝移植受者的預后情況。方法回顧性分析2021 年 3 月至 2024 年 12 月期間中國人民解放軍聯勤保障部隊第九〇〇醫院肝膽胰外科收治的 12 例術前接受ICIs治療的肝癌肝移植受者的臨床資料，總結其術后生存狀態以及并發癥發生情況。結果 12例受者術前應用ICIs治療1～23個周期，從停藥到肝移植的間隔時間為57～475 d。4例受者在術后2周內發生排斥反應，其中3例經糖皮質激素沖擊治療及調整他克莫司劑量后好轉，1例因急性排斥反應死亡。1例受者于術后3周出現藥物性肝損害，經對癥處理后好轉，但后續發生膽管狹窄。1例患者于術后1年因腫瘤復發而死亡。結論 ICIs可用于肝癌肝移植術前治療，但需警惕術后排斥反應的發生，對于遠期膽管并發癥發生的確切影響尚不明確，有待更多臨床研究進一步驗證。

Citation： 杜俊杰, 魏臻煜, 劉建勇, 江藝, 呂立志, 蔡秋程. 術前應用免疫檢查點抑制劑的肝癌肝移植受者預后分析：附12例報道. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2025, 32(11): 1453-1457. doi: 10.7507/1007-9424.202508127 Copy

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. doi: 10.1126/science.aax0182.
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.	劉召波, 武聚山, 林棟棟, 等. PD-1抑制劑用于肝癌肝移植術前治療的安全性探討. 器官移植, 2021, 12(4): 445-449.
7.	崔春曉, 楊柳曉, 王穎, 等. 肝癌患者肝移植術前使用PD-1抑制劑對移植后排斥反應的影響. 中國臨床醫學, 2020, 27(3): 444-447.
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. doi: 10.1186/s40425-017-0284-8.
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. doi: 10.1177/0300060521994406.
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, 9: 1157. doi: 10.3389/fonc.2019.01157.
12.	賓陽陽, 李杰群, 李強, 等. PD-1單克隆抗體治療實體器官移植術后惡性腫瘤的系統評價. 器官移植, 2020, 11(3): 384-390.
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.	師玨玨, 徐鈞, 張海燕, 等. 系統評價巴利昔單抗誘導的無激素免疫抑制方案在肝移植中的有效性. 實用器官移植電子雜志, 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. doi: 10.1126/science.aax0182.
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. 劉召波, 武聚山, 林棟棟, 等. PD-1抑制劑用于肝癌肝移植術前治療的安全性探討. 器官移植, 2021, 12(4): 445-449.
7. 崔春曉, 楊柳曉, 王穎, 等. 肝癌患者肝移植術前使用PD-1抑制劑對移植后排斥反應的影響. 中國臨床醫學, 2020, 27(3): 444-447.
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. doi: 10.1186/s40425-017-0284-8.
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. doi: 10.1177/0300060521994406.
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, 9: 1157. doi: 10.3389/fonc.2019.01157.
12. 賓陽陽, 李杰群, 李強, 等. PD-1單克隆抗體治療實體器官移植術后惡性腫瘤的系統評價. 器官移植, 2020, 11(3): 384-390.
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. 師玨玨, 徐鈞, 張海燕, 等. 系統評價巴利昔單抗誘導的無激素免疫抑制方案在肝移植中的有效性. 實用器官移植電子雜志, 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.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

術前應用免疫檢查點抑制劑的肝癌肝移植受者預后分析：附12例報道

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