Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
Centro de Investigación Biomédica en Red de Enfermedades Hepáticas (CIBEREHD), Madrid, Spain.
Liver Transpl. 2019 May;25(5):771-786. doi: 10.1002/lt.25430. Epub 2019 Apr 5.
In the field of liver transplantation, the demand for adequate allografts greatly exceeds the supply. Therefore, expanding the donor pool to match the growing demand is mandatory. The present review summarizes current knowledge of the pathophysiology of ischemia/reperfusion injury in steatotic grafts, together with recent pharmacological approaches aimed at maximizing the utilization of these livers for transplantation. We also describe the preclinical models currently available to understand the molecular mechanisms controlling graft viability in this specific type of donor, critically discussing the heterogeneity in animal models, surgical methodology, and therapeutic interventions. This lack of common approaches and interventions makes it difficult to establish the pathways involved and the relevance of isolated discoveries, as well as their transferability to clinical practice. Finally, we discuss how new therapeutic strategies developed from experimental studies are promising but that further studies are warranted to translate them to the bedside.
在肝移植领域,合适的供体器官需求量远远超过供应量。因此,扩大供体池以满足不断增长的需求是强制性的。本综述总结了目前关于脂肪肝移植物缺血/再灌注损伤的病理生理学知识,以及最近旨在最大限度地利用这些肝脏进行移植的药理学方法。我们还描述了目前可用于了解控制此类供体移植物活力的分子机制的临床前模型,批判性地讨论了动物模型、手术方法和治疗干预措施的异质性。这种缺乏共同方法和干预措施的情况使得确定所涉及的途径以及孤立发现的相关性及其向临床实践的可转移性变得困难。最后,我们讨论了从实验研究中开发的新治疗策略是有希望的,但需要进一步的研究将它们转化为临床实践。