Department of Surgery, HKU-SZH & Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
Int J Mol Sci. 2021 Jul 30;22(15):8210. doi: 10.3390/ijms22158210.
Liver transplantation has been identified as the most effective treatment for patients with end-stage liver diseases. However, hepatic ischemia reperfusion injury (IRI) is associated with poor graft function and poses a risk of adverse clinical outcomes post transplantation. Cell death, including apoptosis, necrosis, ferroptosis and pyroptosis, is induced during the acute phase of liver IRI. The release of danger-associated molecular patterns (DAPMs) and mitochondrial dysfunction resulting from the disturbance of metabolic homeostasis initiates graft inflammation. The inflammation in the short term exacerbates hepatic damage, leading to graft dysfunction and a higher incidence of acute rejection. The subsequent changes in the graft immune environment due to hepatic IRI may result in chronic rejection, cancer recurrence and fibrogenesis in the long term. In this review, we mainly focus on new mechanisms of inflammation initiated by immune activation related to metabolic alteration in the short term during liver IRI. The latest mechanisms of cancer recurrence and fibrogenesis due to the long-term impact of inflammation in hepatic IRI is also discussed. Furthermore, the development of therapeutic strategies, including ischemia preconditioning, pharmacological inhibitors and machine perfusion, for both attenuating acute inflammatory injury and preventing late-phase disease recurrence, will be summarized in the context of clinical, translational and basic research.
肝移植已被确定为治疗终末期肝病患者的最有效方法。然而，肝缺血再灌注损伤（IRI）与移植物功能不良相关，并在移植后带来不良临床结局的风险。细胞死亡，包括细胞凋亡、细胞坏死、铁死亡和细胞焦亡，在肝 IRI 的急性期诱导。代谢稳态紊乱导致的危险相关分子模式（DAMP）的释放和线粒体功能障碍引发移植物炎症。短期内的炎症会加重肝损伤，导致移植物功能障碍和急性排斥反应的发生率增加。肝 IRI 后移植物免疫环境的后续变化可能导致慢性排斥反应、癌症复发和纤维化。在这篇综述中，我们主要关注与肝 IRI 短期代谢改变相关的免疫激活引发的炎症的新机制。还讨论了肝 IRI 炎症的长期影响导致癌症复发和纤维化的最新机制。此外，还将根据临床、转化和基础研究，总结包括缺血预处理、药理抑制剂和机器灌注在内的治疗策略的发展，以减轻急性炎症损伤和预防后期疾病复发。
