Liver Unit, Queen Elizabeth Hospital, University Hospitals Birmingham NHS Foundation Trust, Birmingham, United Kingdom.
Centre for Liver and Gastrointestinal Research, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, United Kingdom.
Front Immunol. 2020 Oct 19;11:565616. doi: 10.3389/fimmu.2020.565616. eCollection 2020.
Liver transplantation is the only recognized effective treatment for end-stage liver disease. However, organ shortages have become the main challenge for patients and physicians within the transplant community. Waiting list mortality remains an issue with around 10% of patients dying whilst waiting for an available organ. The post-transplantation period is also associated with an adverse complication rate for these specific cohorts of high-risk patients, particularly regarding patient and graft survival. Ischaemia reperfusion injury (IRI) has been highlighted as the mechanism of injury that increases parenchymal damage, which eventually lead to significant graft dysfunction and other poor outcome indicators. The consequences of IRI in clinical practice such as reperfusion syndrome, primary non-function of graft, allograft dysfunction, ischaemic biliary damage and early biliary complications can be life-threatening. IRI dictates the development of a significant inflammatory response that drives the pathway to eventual cell death. The main mechanisms of IRI are mitochondrial damage due to low oxygen tension within the hepatic micro-environment and severe adenosine triphosphate (ATP) depletion during the ischaemic period. After the restoration of normal blood flow, this damage is further enhanced by reoxygenation as the mitochondria respond to reperfusion by releasing reactive oxygen species (ROS), which in turn activate Kupffer cells within the hepatic micro-environment, leading to a pro-inflammatory response and eventual parenchymal cell apoptosis and associated tissue degradation. Machine perfusion (MP) is one emergent strategy considered to be one of the most important advances in organ preservation, restoration and transplantation. Indeed, MP has the potential to rescue frequently discarded organs and has been shown to limit the extent of IRI, leading to suppression of the deleterious pro-inflammatory response. This immunomodulation reduces the prevalence of allograft rejection, the use of immunosuppression therapy and minimizes post-transplant complications. This review aims to update the current knowledge of MP with a focus on normothermic machine liver perfusion (NMLP) and its potential role in immune response pathways.
肝移植是治疗终末期肝病的唯一有效方法。然而，器官短缺已成为移植领域患者和医生面临的主要挑战。约有 10%的等待器官移植的患者在等待过程中死亡，这仍然是一个问题。对于这些高危患者群体，移植后期间也与不良并发症发生率相关，特别是在患者和移植物存活率方面。缺血再灌注损伤 (IRI) 已被确定为增加实质损伤的损伤机制，最终导致显著的移植物功能障碍和其他不良预后指标。IRI 在临床实践中的后果，如再灌注综合征、移植物原发性无功能、同种异体移植物功能障碍、缺血性胆管损伤和早期胆管并发症，可能危及生命。IRI 决定了炎症反应的发展，炎症反应驱动着最终细胞死亡的途径。IRI 的主要机制是肝微环境中低氧张力引起的线粒体损伤和缺血期间严重的三磷酸腺苷 (ATP) 耗竭。在恢复正常血流后，由于线粒体通过释放活性氧物质 (ROS) 对再灌注做出反应，这种损伤进一步加剧，ROS 继而激活肝微环境中的枯否细胞，导致促炎反应和最终实质细胞凋亡以及相关组织降解。机器灌注 (MP) 是一种新兴策略，被认为是器官保存、恢复和移植的最重要进展之一。事实上，MP 有可能挽救经常被丢弃的器官，并已被证明可以限制 IRI 的程度，从而抑制有害的促炎反应。这种免疫调节可降低同种异体移植物排斥反应的发生率、免疫抑制治疗的使用，并最大限度地减少移植后并发症。本综述旨在更新 MP 的最新知识，重点介绍常温机器肝灌注 (NMLP) 及其在免疫反应途径中的潜在作用。
