Rudolph Mark, Shah Shimul A, Quillin Ralph, Lemon Kristina, Olowokure Olugbenga, Latif Tahir, Sohal Davendra
Division of Hematology/Oncology, Department of Internal Medicine, University of Cincinnati, Cincinnati, OH, USA.
Division of Transplantation, Department of Surgery, University of Cincinnati, Cincinnati, OH, USA.
J Gastrointest Oncol. 2023 Apr 29;14(2):1141-1148. doi: 10.21037/jgo-22-922. Epub 2023 Apr 3.
Immune checkpoint inhibitors (ICIs) in the setting of liver transplant (LT) pose a risk of rejection and hold unclear benefit in both the neoadjuvant (pre-transplant) and post-transplant salvage setting. In the pre-transplant setting, neoadjuvant ICIs may serve as a bridge to LT by downstaging disease burden to fit within transplant criteria. Outcomes in this setting include patients who had successful transplants without complications to patients who suffered severe complications, including fatal hepatic necrosis and graft failure requiring re-transplant. Some authors suggest having a period of three months between checkpoint inhibition and transplant may help mitigate adverse effects. In the post-LT setting, there are few treatment options if there is a recurrence of disease, which forces treatment teams to reconsider checkpoint inhibitors. Again, a longer period of time between transplant and checkpoint inhibition may reduce risk of rejection. Case reports of patients treated with ICIs post-transplant utilized either nivolumab or pembrolizumab. As combination atezolizumab/bevacizumab is a relatively new treatment option for unresectable hepatocellular carcinoma (HCC), there are only three reported cases using this combination in the post-LT setting. While there were no cases of rejection, all three cases had progression of disease. As immunotherapy joins transplantation as a mainstay of treatment for HCC, it remains unclear how to best navigate when the treatment course involves both immune activation and immunosuppression.
Patients who had an LT and were treated with ICIs (pre or post LT) at the University of Cincinnati were included in this retrospective chart review.
Fatal rejection remains a significant risk even 4 years after LT. Neoadjuvant ICIs also pose a risk for acute cellular rejection; however, this may not always be clinically significant. Graft versus host disease (GVHD) may be an additional, previously unreported risk of ICIs in the setting of LT. Prospective studies are needed to understand benefits and risks of checkpoint inhibitors in the LT setting.
肝移植（LT）背景下的免疫检查点抑制剂（ICI）存在排斥风险，且在新辅助（移植前）和移植后挽救治疗中获益不明。在移植前阶段，新辅助ICI可通过降低疾病负担以符合移植标准，从而作为LT的桥梁。此阶段的结果包括成功移植且无并发症的患者，以及出现严重并发症（包括致命性肝坏死和需要再次移植的移植物功能衰竭）的患者。一些作者建议在检查点抑制和移植之间间隔三个月可能有助于减轻不良反应。在LT后阶段，如果疾病复发，治疗选择很少，这迫使治疗团队重新考虑检查点抑制剂。同样，移植和检查点抑制之间较长的时间间隔可能会降低排斥风险。移植后接受ICI治疗的患者的病例报告使用的是纳武单抗或派姆单抗。由于阿特珠单抗/贝伐单抗联合用药是不可切除肝细胞癌（HCC）的一种相对较新的治疗选择，在LT后阶段使用这种联合用药的报告病例仅有三例。虽然没有排斥病例，但所有三例均有疾病进展。随着免疫疗法成为HCC治疗的主要手段之一，当治疗过程涉及免疫激活和免疫抑制时，如何最佳应对仍不明确。
纳入了在辛辛那提大学接受LT并接受ICI治疗（移植前或移植后）的患者进行这项回顾性图表审查。
即使在LT后4年，致命性排斥仍然是一个重大风险。新辅助ICI也有急性细胞排斥的风险；然而，这在临床上可能并不总是具有显著意义。移植物抗宿主病（GVHD）可能是LT背景下ICI的另一种此前未报告的风险。需要进行前瞻性研究以了解LT背景下检查点抑制剂的益处和风险。
