移植前使用免疫检查点抑制剂治疗肝细胞癌:一项多中心回顾性队列研究。

Pretransplant use of immune checkpoint inhibitors for hepatocellular carcinoma: A multicenter, retrospective cohort study.

机构信息

Organ Transplant Centre, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China; Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, China; Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), Guangzhou, China; NHC Key Laboratory of Assisted Circulation (Sun Yat-sen University), Guangzhou, China.

Organ Transplant Centre, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China; Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, China; Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), Guangzhou, China.

出版信息

Am J Transplant. 2024 Oct;24(10):1837-1856. doi: 10.1016/j.ajt.2024.04.007. Epub 2024 Apr 18.

Abstract

Immune checkpoint inhibitors (ICIs) as a downstaging or bridging therapy for liver transplantation (LT) in hepatocellular carcinoma patients are rapidly increasing. However, the evidence about the feasibility and safety of pre-LT ICI therapy is limited and controversial. To this end, a multicenter, retrospective cohort study was conducted in 11 Chinese centers. The results showed that 83 recipients received pre-LT ICI therapy during the study period. The median post-LT follow-up was 8.1 (interquartile range 3.3-14.6) months. During the short follow-up, 23 (27.7%) recipients developed allograft rejection, and 7 of them (30.4%) were diagnosed by liver biopsy. Multivariate logistics regression analysis showed that the time interval between the last administration of ICI therapy and LT (TLAT) ≥ 30 days was an independent protective factor for allograft rejection (odds ratio = 0.096, 95% confidence interval 0.026-0.357; P < .001). Multivariate Cox analysis showed that allograft rejection was an independent risk factor for overall survival (hazard ratio = 9.960, 95% confidence interval 1.006-98.610; P = .043). We conclude that patients who receive a pre-LT ICI therapy with a TLAT shorter than 30 days have a much higher risk of allograft rejection than those with a TLAT longer than 30 days. The presence of rejection episodes might be associated with higher post-LT mortality.

摘要

免疫检查点抑制剂(ICI)作为肝癌患者肝移植(LT)的降期或桥接治疗方法正在迅速增加。然而,关于 LT 前 ICI 治疗的可行性和安全性的证据有限且存在争议。为此,在中国的 11 个中心进行了一项多中心、回顾性队列研究。结果显示,在研究期间,83 名受者接受了 LT 前 ICI 治疗。LT 后中位随访时间为 8.1 个月(四分位距 3.3-14.6)。在短暂的随访中,23 名(27.7%)受者发生了移植物排斥反应,其中 7 名(30.4%)通过肝活检诊断。多变量逻辑回归分析显示,ICI 治疗最后一次给药与 LT 之间的时间间隔(TLAT)≥30 天是移植物排斥反应的独立保护因素(比值比=0.096,95%置信区间 0.026-0.357;P<0.001)。多变量 Cox 分析显示,移植物排斥反应是总生存的独立危险因素(风险比=9.960,95%置信区间 1.006-98.610;P=0.043)。我们得出结论,TLAT 短于 30 天的 LT 前 ICI 治疗患者发生移植物排斥反应的风险明显高于 TLAT 长于 30 天的患者。排斥反应的发生可能与 LT 后更高的死亡率有关。

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