Kahramangil Doga, Zarrinpar Ali, Sahin Ilyas
Department of Internal Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Department of Surgery, University of Florida College of Medicine, Gainesville, Florida, USA.
Liver Transpl. 2024 Dec 16. doi: 10.1097/LVT.0000000000000550.
Immune checkpoint inhibitors (ICIs) have shown promise in the treatment of HCC. However, their safety and efficacy in recipients of liver transplants with recurrent HCC remain unclear. This systematic review aims to evaluate the use of ICIs for recurrent HCC after liver transplantation (LT) and to identify potential predictive factors associated with graft rejection and treatment response. A comprehensive literature search was conducted using PubMed and Scopus databases to identify case reports and case series describing the use of ICIs for HCC recurrence after LT. Data on patient characteristics, treatment details, and outcomes were extracted and analyzed. Twenty-one case reports and case series involving 39 patients were included. The median time from LT to ICI initiation was 24 months. Nivolumab was the most commonly used ICI (59.0%). Among all cases, 25.6% demonstrated a positive response, including stable disease and partial or complete response, while 46.2% experienced progressive disease. Graft rejection occurred in 20.5% of patients, with 50% of these cases resulting in death. Although reported in only some of the cases (17 out of 39), positive programmed cell death ligand-1 expression was associated with a higher risk of graft rejection (66.7%) compared to negative expression (0%). calcineurin inhibitors-based immunosuppressive regimens appeared to have lower rejection rates (20%) compared to mammalian target of rapamycin inhibitor-based regimens (80%). ICIs show potential for treating recurrent HCC after LT, but the risk of graft rejection is significant. Careful patient selection, close monitoring, and individualized management of immunosuppression are crucial. Positive programmed cell death ligand-1 expression and the choice of immunosuppressive regimen appear to influence the risk of graft rejection; however, these findings are based on limited data. Prospective studies with larger sample sizes are needed to validate these findings and establish evidence-based guidelines for the use of ICIs in the posttransplant setting.
免疫检查点抑制剂（ICIs）在肝癌治疗中已显示出前景。然而，它们在复发性肝癌肝移植受者中的安全性和疗效仍不清楚。本系统评价旨在评估ICIs在肝移植（LT）后复发性肝癌中的应用，并确定与移植物排斥和治疗反应相关的潜在预测因素。使用PubMed和Scopus数据库进行了全面的文献检索，以识别描述ICIs用于LT后肝癌复发的病例报告和病例系列。提取并分析了患者特征、治疗细节和结局的数据。纳入了涉及39例患者的21篇病例报告和病例系列。从LT到开始使用ICIs的中位时间为24个月。纳武单抗是最常用的ICIs（59.0%）。在所有病例中，25.6%表现出阳性反应，包括疾病稳定以及部分或完全缓解，而46.2%经历疾病进展。20.5%的患者发生移植物排斥，其中50%的病例导致死亡。尽管仅在部分病例（39例中的17例）中报告，但程序性细胞死亡配体-1表达阳性与移植物排斥风险较高（66.7%）相关，而阴性表达者（0%）则无此情况。与基于雷帕霉素靶蛋白抑制剂的免疫抑制方案（80%）相比，基于钙调神经磷酸酶抑制剂的免疫抑制方案似乎具有较低的排斥率（20%）。ICIs显示出治疗LT后复发性肝癌的潜力，但移植物排斥风险显著。仔细的患者选择、密切监测和免疫抑制的个体化管理至关重要。程序性细胞死亡配体-1表达阳性和免疫抑制方案的选择似乎会影响移植物排斥风险；然而，这些发现基于有限的数据。需要更大样本量的前瞻性研究来验证这些发现，并为移植后使用ICIs建立循证指南。
