据报道，在肝移植（LT）之前使用免疫检查点抑制剂（ICIs）治疗肝细胞癌（HCC）；然而，ICIs 可能会增加同种异体移植排斥的风险并影响其他临床结果。本研究旨在总结 ICI 使用对 LT 后结果的影响。在这项个体患者数据荟萃分析中，我们检索了数据库以识别 LT 前接受 ICI 治疗的 HCC 病例，详细说明同种异体移植排斥、HCC 复发和总体生存率。我们进行了 Cox 回归分析，以确定同种异体移植排斥的危险因素。在 91 名符合条件的患者中，中位（四分位距 [IQR]）随访时间为 690.0 (654.5) 天，其中有 24 例 (26.4%) 同种异体移植排斥，9 ( 9.9%）HCC 复发，9 例（9.9%）死亡。年龄（调整后的风险比 [aHR] 每 10 年=0.72，95% 置信区间 [CI]=0.53、0.99，P=0.044）和 ICI 清除时间（每 1 周 aHR=0.92，95% CI=0.86、0.99， P=0.022）与同种异体移植排斥相关。同种异体移植排斥概率≤20%的患者的中位（IQR）清除期为94（196）天。有和没有同种异体移植排斥的病例之间的总生存率没有差异（对数秩检验，p=0.2）。 HCC 复发个体的中位 (IQR) ICI 周期数少于未复发个体 (4.0 [1.8]) 与 8.0 [9.0]）； p=0.025）。米兰地区 ICI 后复发患者的比例低于未复发患者（16.7% vs. 65.3%，p=0.032） 结论：患者在 ICI 治疗后具有可接受的 LT 后结局。年龄和 ICI 清除时间长短与同种异体移植排斥风险相关，3 个月的清除可能会将其降低至未暴露于 ICI 的患者。 ICI 周期数和肿瘤负荷可能会影响复发风险。需要进行大型前瞻性研究来证实这些关联。这项对 91 名肝细胞癌患者和肝移植前使用免疫检查点抑制剂的患者进行的系统回顾和个体患者数据荟萃分析表明，总体移植后结果是可接受的。年龄较大和免疫检查点抑制剂清除期较长与同种异体移植排斥的风险呈显着负相关。 3 个月的清除可能会将其降低至未暴露于 ICI 的患者的水平。此外，免疫治疗完成时米兰标准内的免疫检查点抑制剂周期数和肿瘤负荷的增加可能预示着肝细胞癌复发风险的降低，但这一观察结果需要在更大规模的前瞻性研究中进一步验证。国际前瞻性系统评价登记册代码 (PROSPERO)：CRD42023494951。版权所有 © 2024。由 Elsevier B.V. 出版

Treatment with immune checkpoint inhibitors (ICIs) for hepatocellular carcinoma (HCC) prior to liver transplantation (LT) has been reported; however, ICIs may elevate the risk of allograft rejection and impact other clinical outcomes. This study aims to summarize the impact of ICI use on post-LT outcomes.In this individual patient data meta-analysis, we searched databases to identify HCC cases treated with ICIs before LT, detailing allograft rejection, HCC recurrence, and overall survival. We performed Cox regression analysis to identify risk factors for allograft rejection.Among 91 eligible patients, with a median (interquartile range [IQR]) follow-up of 690.0 (654.5) days, there were 24 (26.4%) allograft rejections, 9 (9.9%) HCC recurrences, and 9 (9.9%) deaths. Age (adjusted hazard ratio [aHR] per 10 years=0.72, 95% confidence interval [CI]=0.53, 0.99, P=0.044) and ICI washout time (aHR per 1 week=0.92, 95% CI=0.86, 0.99, P=0.022) were associated with allograft rejection. The median (IQR) washout period for patients with ≤20% probability of allograft rejection was 94 (196) days. Overall survival did not differ between cases with and without allograft rejection (log-rank test, p=0.2). Individuals with HCC recurrence had fewer median (IQR) ICI cycles than those without recurrence (4.0 [1.8]) vs. 8.0 [9.0]); p=0.025). The proportion of patients within Milan post-ICI was lower for those with recurrence vs. without (16.7% vs. 65.3%, p=0.032) CONCLUSION: Patients have acceptable post-LT outcomes after ICI therapy. Age and ICI washout length relate to the allograft rejection risk, and a 3-month washout may reduce it to that of patients without ICI exposure. Number of ICI cycles and tumor burden may affect recurrence risk. Large prospective studies are necessary to confirm these associations.This systematic review and individual patient data meta-analysis of 91 patients with hepatocellular carcinoma and immune checkpoint inhibitors use prior to liver transplantation suggests acceptable overall post-transplant outcomes. Older age and longer immune checkpoint inhibitor washout period have a significant inverse association with the risk of allograft rejection. A 3-month washout may reduce it to that of patients without ICI exposure. Additionally, a higher number of immune checkpoint inhibitor cycles and tumor burden within Milan criteria at the completion of immunotherapy may predict a decreased risk of hepatocellular carcinoma recurrence, but this observation requires further validation in larger prospective studies. CODE FOR INTERNATIONAL PROSPECTIVE REGISTER OF SYSTEMATIC REVIEWS (PROSPERO): CRD42023494951.Copyright © 2024. Published by Elsevier B.V.