Department of Surgery Sciences, HPB and Transplant Unit, University of Tor Vergata, Rome 00100, Italy.
Hepatology Unit, University of Tor Vergata, Rome 00100, Italy.
World J Gastroenterol. 2021 Dec 7;27(45):7771-7783. doi: 10.3748/wjg.v27.i45.7771.
Chronic rejection (CR) of liver allografts causes damage to intrahepatic vessels and bile ducts and may lead to graft failure after liver transplantation. Although its prevalence has declined steadily with the introduction of potent immunosuppressive therapy, CR still represents an important cause of graft injury, which might be irreversible, leading to graft loss requiring re-transplantation. To date, we still do not fully appreciate the mechanisms underlying this process. In addition to T cell-mediated CR, which was initially the only recognized type of CR, recently a new form of liver allograft CR, antibody-mediated CR, has been identified. This has indeed opened an era of thriving research and renewed interest in the field. Liver biopsy is needed for a definitive diagnosis of CR, but current research is aiming to identify new non-invasive tools for predicting patients at risk for CR after liver transplantation. Moreover, the minimization or withdrawal of immunosuppressive therapy might influence the establishment of subclinical CR-related injury, which should not be disregarded. Therapies for CR may only be effective in the "early" phases, and a tailored management of the immunosuppression regimen is essential for preventing irreversible liver damage. Herein, we provide an overview of the current knowledge and research on CR, focusing on early detection, identification of non-invasive biomarkers, immunosuppressive management, re-transplantation and future perspectives of CR.
慢性排斥反应（CR）会导致肝移植后肝内血管和胆管损伤，并可能导致移植物失功。尽管随着强效免疫抑制治疗的引入，其患病率稳步下降，但 CR 仍然是导致移植物损伤的重要原因，而且这种损伤可能是不可逆的，导致需要再次移植。迄今为止，我们仍不完全了解这一过程的机制。除了最初被认为是唯一类型的 CR 的 T 细胞介导的 CR 外，最近还发现了一种新的肝移植 CR，即抗体介导的 CR。这确实开启了一个研究蓬勃发展和重新引起人们兴趣的时代。肝活检是诊断 CR 的明确诊断方法，但目前的研究旨在确定新的非侵入性工具，以预测肝移植后发生 CR 的风险患者。此外，最小化或撤回免疫抑制治疗可能会影响亚临床 CR 相关损伤的建立，不应忽视这一点。CR 的治疗方法可能仅在“早期”阶段有效，因此必须对免疫抑制方案进行个体化管理，以防止不可逆转的肝损伤。在此，我们概述了目前对 CR 的认识和研究，重点介绍了早期检测、非侵入性生物标志物的识别、免疫抑制管理、再次移植以及 CR 的未来展望。
