Liver Unit, Queen Elizabeth Hospital, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK.
National Institute for Health Research (NIHR) Birmingham Biomedical Research Centre, Institute of Immunology and Immunotherapy, College of Medical and Dental Sciences, University of Birmingham, UK.
Am J Transplant. 2018 Oct;18(10):2384-2399. doi: 10.1111/ajt.14992. Epub 2018 Jul 24.
Long-standing research has shown that increased lipid content in donor livers is associated with inferior graft outcomes posttransplant. The global epidemic that is obesity has increased the prevalence of steatosis in organ donors, to the extent that it has become one of the main reasons for declining livers for transplantation. Consequently, it is one of the major culprits behind the discrepancy between the number of donor livers offered for transplantation and those that go on to be transplanted. Steatotic livers are characterized by poor microcirculation, depleted energy stores because of an impaired capacity for mitochondrial recovery, and a propensity for an exaggerated inflammatory response following reperfusion injury culminating in poorer graft function postoperatively. Ex situ machine perfusion, currently a novel method in graft preservation, is showing great promise in providing a tool for the recovery and reconditioning of marginal livers. Hence, reconditioning these steatotic livers using machine perfusion has the potential to increase the number of liver transplants performed. In this review, we consider the problematic issues associated with fatty livers in the realm of transplantation and discuss pharmacological and nonpharmacological options that are being developed to enhance recovery of these organs using machine perfusion and defatting strategies.
长期以来的研究表明,供体肝脏中的脂质含量增加与移植后移植物的不良结局有关。肥胖是全球性的流行疾病,导致器官捐献者中的脂肪变性患病率增加,以至于它已成为移植肝脏减少的主要原因之一。因此,它是导致可供移植的供体肝脏数量与实际移植数量之间存在差异的主要原因之一。脂肪变性的肝脏表现为微循环不良、由于线粒体恢复能力受损而能量储备减少,以及再灌注损伤后炎症反应过度,导致术后移植物功能较差。离体机器灌注是一种新型的供体保存方法,目前显示出在恢复和调理边缘性肝脏方面有很大的潜力。因此,使用机器灌注对这些脂肪变性的肝脏进行调理有可能增加肝移植的数量。在这篇综述中,我们考虑了与移植领域中脂肪肝相关的问题,并讨论了正在开发的药理学和非药理学选择,以使用机器灌注和脱脂策略增强这些器官的恢复。