Marino Rebecca, Hassan Ahmed Talaat, Fagenson Alexander, Tabrizian Parissa
Liver Transplant and Hepatobiliary Surgery, Recanati-Miller Transplantation Institute, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy, New York, New York, USA.
Curr Opin Organ Transplant. 2025 May 6. doi: 10.1097/MOT.0000000000001228.
To explore the emerging use of immune checkpoint inhibitors (ICIs) in hepatocellular carcinoma (HCC) patients eligible for liver transplantation (LT), particularly as bridging and downstaging therapies. This review also addresses the clinical challenges of integrating ICIs into transplant protocols, including graft rejection, immune-related toxicities, and gaps in evidence.
ICIs have shown potential as bridging and downstaging therapies before LT, with multicentric studies reporting 75.6% successful downstaging, 85% 3-year post-LT survival, and 7.2% rejection-related mortality. A washout interval >94 days and older age have been identified as protective factors against allograft rejection. Combining locoregional therapies with ICIs has proven effective in the EMERALD-1 and LEAP-012 trials, which demonstrated improved progression-free survival (15.0 and 14.6 months, respectively) with ICI-TACE combinations. Similarly, the STAR-FIT phase II trial, combining TACE, SBRT, and avelumab, showed a 42% complete response rate and 12% conversion to curative therapy. Toxicity and rejection risk remain major challenges.
ICIs represent a promising tool for expanding transplant eligibility in HCC, but their integration into LT pathways remains complex. Safety concerns, particularly regarding timing and immune modulation, require careful evaluation. Prospective studies and biomarker development are needed to guide clinical decision-making. Novel therapies such as CAR-T cells may offer more targeted approaches in the future.
探讨免疫检查点抑制剂（ICI）在适合肝移植（LT）的肝细胞癌（HCC）患者中的新兴应用，特别是作为桥接和降期治疗。本综述还讨论了将ICI纳入移植方案的临床挑战，包括移植物排斥、免疫相关毒性和证据空白。
ICI已显示出作为LT前桥接和降期治疗的潜力，多中心研究报告降期成功率为75.6%，LT后3年生存率为85%，与排斥相关的死亡率为7.2%。洗脱间隔>94天和年龄较大已被确定为防止同种异体移植排斥的保护因素。在EMERALD-1和LEAP-012试验中，局部区域治疗与ICI联合已被证明有效，ICI-经动脉化疗栓塞（TACE）联合方案显示无进展生存期改善（分别为15.0和14.6个月）。同样，STAR-FIT II期试验联合TACE、立体定向体部放疗（SBRT）和阿维鲁单抗，显示完全缓解率为42%，转化为根治性治疗的比例为12%。毒性和排斥风险仍然是主要挑战。
ICI是扩大HCC移植适应证的一种有前景的工具，但将其纳入LT途径仍然复杂。安全问题，特别是关于时机和免疫调节，需要仔细评估。需要前瞻性研究和生物标志物开发来指导临床决策。诸如嵌合抗原受体T细胞（CAR-T）等新型疗法未来可能提供更具针对性的方法。
