Ma Delin, Wei Pengcheng, Cheng Qian, Hao Jialing, Li Zuyin, Chen Zhuomiaoyu, Shi Wenzai, Yuan Zhigao, Lo Chen, Luo Yongjing, Qiao Liyi, Gao Jie, Zhu Jiye, Li Zhao
Department of Hepatobiliary Surgery, Peking University People's Hospital, Beijing, China.
Beijing Key Laboratory of HCC and Liver Cirrhosis, Peking University People's Hospital, Beijing, China.
BMC Med. 2025 Sep 2;23(1):515. doi: 10.1186/s12916-025-04352-z.
Hepatocellular carcinoma (HCC) remains a major contributor to global cancer mortality, with liver transplantation (LT) offering curative potential for patients in the early stages. While immune checkpoint inhibitors (ICIs) are effective in managing tumor progression, concerns about graft rejection persist. This study investigates how peri-LT ICIs administration affects rejection rates and survival outcomes in HCC patients.
This global study analyzed 386 HCC patients receiving Peri-LT ICIs therapy, integrating data from a systematic literature review and institutional registries. The risk of graft rejection and survival outcomes were assessed using logistic and Cox regression, along with restricted cubic splines modeling dose-response dynamics.
Overall graft rejection rates did not significantly differ between Pre-LT (17.5%) and Post-LT (22.1%) ICI users (P = 0.351); however, Post-LT use was associated with higher rates of graft loss/dysfunction (47.1% vs. 25.9%, P < 0.05) and rejection-related mortality (47.1% vs. 18.5%, P < 0.05). In Pre-LT patients, washout periods >30 days (OR = 0.36, 95% CI: 0.18-0.72, P = 0.004) and >1.5 half-life counts (OR = 0.24, 95% CI: 0.12-0.50, P < 0.001) were associated with reduced rejection risk. Post-LT, high PD-L1 expression on graft tissue correlated with increased rejection risk (P < 0.001). Graft rejection following Pre-LT ICIs was linked to poorer overall survival (HR = 5.17, 95% CI: 2.21-12.24, P < 0.001).
With careful management, peri-LT ICIs may be considered for HCC patients. Optimizing washout periods and monitoring graft PD-L1 expression may improve transplant outcomes.
肝细胞癌（HCC）仍是全球癌症死亡的主要原因，肝移植（LT）为早期患者提供了治愈的可能性。虽然免疫检查点抑制剂（ICIs）在控制肿瘤进展方面有效，但对移植物排斥的担忧依然存在。本研究调查了肝移植围手术期使用ICIs如何影响HCC患者的排斥率和生存结果。
这项全球研究分析了386例接受肝移植围手术期ICIs治疗的HCC患者，整合了系统文献综述和机构登记处的数据。使用逻辑回归和Cox回归评估移植物排斥风险和生存结果，并使用受限立方样条模型分析剂量反应动态。
肝移植前（17.5%）和肝移植后（22.1%）使用ICIs的患者总体移植物排斥率无显著差异（P = 0.351）；然而，肝移植后使用与更高的移植物丢失/功能障碍率（47.1%对25.9%，P < 0.05）和排斥相关死亡率（47.1%对18.5%，P < 0.05）相关。在肝移植前患者中，洗脱期>30天（OR = 0.36，95% CI：0.18 - 0.72，P = 0.004）和>1.5个半衰期计数（OR = 0.24，95% CI：0.12 - 0.50，P < 0.001）与排斥风险降低相关。肝移植后，移植物组织上高PD-L1表达与排斥风险增加相关（P < 0.001）。肝移植前使用ICIs后的移植物排斥与较差的总生存率相关（HR = 5.17，95% CI：2.21 - 12.24，P < 0.001）。
经过谨慎管理，肝移植围手术期ICIs可考虑用于HCC患者。优化洗脱期和监测移植物PD-L1表达可能改善移植结果。
