程序性死亡受体(PD)-1单克隆抗体治疗肝癌肝移植术后复发诱发急性免疫性肝炎:附1例报告

Programmed death receptor( PD)-1 monoclonal antibody-induced acute immune hepatitis in the treatment of recurrent hepatocellular carcinoma after liver transplantation: a case report

目的探讨程序性死亡受体(PD)-1单克隆抗体治疗肝细胞癌(肝癌)肝移植术后复发的安全性。方法回顾性分析1例因使用PD-1单克隆抗体(pembrolizumab)治疗肝癌肝移植后复发而诱发急性免疫性肝炎患者的临床资料。结果患者因原发性肝癌行肝移植术,术后4个月发现肝癌肺转移,术后12个月予pembrolizumab治疗(150 mg静脉滴注1次),治疗后第5日发现肝功能异常,行肝穿刺活组织检查病理提示轻至中度急性排斥反应。结合患者临床表现、实验室检查以及pembrolizumab的药物说明书,诊断为急性免疫性肝炎。给予肾上腺皮质激素及加强免疫抑制治疗,随访8个月患者带瘤生存,但肝功能仍持续异常。结论肝移植术后免疫抑制状态下不宜应用PD-1单克隆抗体等免疫检查点抑制剂,有诱发免疫性肝炎的风险。

Objective To explore the safety of programmed death receptor（ PD）-1 monoclonal antibody for treatment of hepatocellular carcinoma（ HCC） recurrence after liver transplantation. Methods Clinical data of 1 case with acute immune hepatitis induced by PD-1 monoclonal antibody（ pembrolizumab） therapy for recurrent HCC after liver transplantation was retrospectively analyzed. Results The patient who received liver transplantation for primary HCC was diagnosed with lung metastasis at 4 months after the transplantation,and treated with the pembrolizumab（ 150 mg intravenous infusion of once） at 12 months after transplantation. Liver dysfunction was found at 5thd after treatment,and liver biopsy was conducted which showed pathological changes of mild to moderate acute rejection. It was diagnosed to be acute immune hepatitis based on the patient ＇s clinical manifestations,laboratory examination and pembrolizumab drug instructions. After adrenal cortical hormone and intensive immunosuppressive therapy,the patient was followed up for 8months,which showed that the patient survived with tumor,but the liver function remained abnormal. Conclusions PD-1monoclonal antibody and other immune checkpoint inhibitors are not suitable for the immunologic suppression after liver transplantation due to the risk of inducing immune hepatitis.