Liver Allograft Failure After Nivolumab Treatment-A Case Report With Systematic Literature Research.
Liver Allograft Failure After Nivolumab Treatment-A Case Report With Systematic Literature Research.
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DOI：
10.1097/txd.0000000000000814
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发表时间：
2018-08
影响因子：
2.3
通讯作者：
Misselwitz B
中科院分区：
文献类型：
--
作者：
Gassmann D;Weiler S;Mertens JC;Reiner CS;Vrugt B;Nägeli M;Mangana J;Müllhaupt B;Jenni F;Misselwitz B
原位肝移植（OLT）是肝细胞癌（HCC）患者的一种潜在治疗方法；然而，OLT 后复发性 HCC 的治疗选择有限。免疫检查点抑制剂，例如纳武单抗（一种程序性细胞死亡蛋白 1 的抑制剂）已成功用于转移性 HCC，但有关实体器官移植后纳武单抗安全性的数据有限。我们报告了一名 53 岁的 HCC 女性接受了 OLT 治疗。 2年后，HCC复发。由于副作用和疾病进展，索拉非尼的初始治疗已停止。随后用纳武单抗治疗肺部和淋巴结中的进展性 HCC。第一次纳武单抗给药一周后，出现快速进展的肝功能障碍。肝活检显示严重的细胞移植排斥反应，提示使用静脉注射类固醇和他克莫司进行治疗。肝功能持续下降，导致严重的凝血功能障碍。患者因颅内出血死亡。系统的 PubMed 搜索显示，有 29 例实体器官移植后接受检查点抑制剂治疗的病例。 11 例 OLT 病例中有 4 例（36%）发生移植物丢失，13 例肾移植后有 7 例（54%）发生移植物丢失。然而，也描述了具有良好结果的案例。通过搜索世界卫生组织数据库 VigiBase，发现了 18 例出现不良事件的病例，其中 2 例是肝移植受者因移植物丢失而导致死亡的病例。在实体器官移植受者中使用检查点抑制剂的经验有限。迄今为止已发表的病例表明，移植物丢失的严重风险高达 36% 至 54%。
Orthotopic liver transplantation (OLT) is a potential curative treatment in patients with hepatocellular carcinoma (HCC); however, treatment options for recurrent HCC after OLT are limited. Immune checkpoint inhibitors, such as nivolumab, an inhibitor of programmed cell death protein 1, have been successfully used for metastatic HCC but data on safety of nivolumab following solid organ transplantation are limited. We report a 53-year-old woman with HCC who was treated with OLT. After 2 years, HCC recurred. Initial treatment with sorafenib was discontinued due to side effects and disease progression. Progressive HCC in the lung and lymph nodes was subsequently treated with nivolumab. One week after the first nivolumab dose, rapid progressive liver dysfunction was noted. Liver biopsy revealed severe cellular graft rejection prompting treatment with intravenous steroids and tacrolimus. Liver function continued to decline, leading to severe coagulopathy. The patient succumbed to intracranial hemorrhage. A systematic PubMed search revealed 29 cases treated with a checkpoint inhibitor following solid organ transplantation. Loss of graft was described in 4 (36%) of 11 cases with OLT and in 7 (54%) of 13 cases after kidney transplantation. However, cases with favorable outcome were also described. Eighteen cases with adverse events were identified upon searching the World Health Organization database VigiBase, including 2 cases with fatal outcome in liver transplant recipients due to graft loss. Experience with checkpoint inhibitors in solid organ transplant recipients is limited. Published cases so far suggest severe risks for graft loss as high as 36% to 54%.