PD-1抑制剂用于肝癌肝移植术前治疗的安全性探讨

目的  探讨程序性细胞死亡蛋白1（PD-1）抑制剂用于原发性肝癌（肝癌）肝移植术前治疗的安全性。 方法  回顾性分析7例术前应用PD-1抑制剂的肝癌肝移植受者的临床资料，总结受者免疫相关不良反应（irAE）发生情况及预后情况，评估PD-1抑制剂在肝癌肝移植受者中使用的安全性。 结果  7例肝癌肝移植受者术前使用PD-1抑制剂，使用疗程为1~20个，自停药至手术间隔时间为6~120 d。5例受者发生不同程度的irAE，其中疲乏3例、发热2例、脱发2例、皮疹2例、腹泻1例、恶心1例、心肌炎1例，多数irAE毒性分级为G1~2级，1例发生G5级毒性反应（致死性心肌炎），并导致受者死亡。1例受者于术后7 d发生排斥反应，经糖皮质激素冲击治疗及增加他克莫司剂量后好转。 结论  PD-1抑制剂可用于肝癌肝移植术前治疗，但应密切注意其irAE及术后排斥反应的发生。

Safety of PD-1 inhibitor in preoperative treatment of liver transplantation for liver cancer

Objective To evaluate the safety of programmed cell death protein 1 (PD-1) inhibitor in the treatment of primary liver cancer (liver cancer) before liver transplantation. Methods Clinical data of 7 recipients given with PD-1 inhibitor before liver transplantation for liver cancer were retrospectively analyzed. The incidence of immune-related adverse event (irAE) and clinical prognosis of the recipients were summarized. The safety of PD-1 inhibitor in recipients prior to liver transplantation for liver cancer was evaluated. Results Seven recipients were treated with PD-1 inhibitor with 1-20 courses before liver transplantation for liver cancer. The time interval from drug withdrawal to liver transplantation was 6-120 d. Five recipients suffered from irAE of different degrees, including fatigue in 3 cases, fever in 2 cases, alopecia in 2 cases, rash in 1 case, nausea in 1 case and myocarditis in 1 case, respectively. A majority of these irAE were classified as grade Ⅰ-Ⅱ. One recipient died from grade Ⅴ irAE (fatal myocarditis). One recipient developed rejection at postoperative 7 d, which were mitigated after glucocorticoid pulse therapy combined with increased dosage of tacrolimus. Conclusions PD-1 inhibitor can be applied in preoperative treatment before liver transplantation for liver cancer. Nevertheless, the incidence of irAE and postoperative rejection should be intimately monitored.