Department of Biomedical Engineering, Rutgers University, Piscataway, NJ, USA.
Am J Transplant. 2012 Dec;12(12):3176-83. doi: 10.1111/j.1600-6143.2012.04288.x. Epub 2012 Oct 11.
Macrovesicular steatosis in greater than 30% of hepatocytes is a significant risk factor for primary graft nonfunction due to increased sensitivity to ischemia reperfusion (I/R) injury. The growing prevalence of hepatic steatosis due to the obesity epidemic, in conjunction with an aging population, may negatively impact the availability of suitable deceased liver donors. Some have suggested that metabolic interventions could decrease the fat content of liver grafts prior to transplantation. This concept has been successfully tested through nutritional supplementation in a few living donors. Utilization of deceased donor livers, however, requires defatting of explanted organs. Animal studies suggest that this can be accomplished by ex vivo warm perfusion in a time scale of a few hours. We estimate that this approach could significantly boost the size of the donor pool by increasing the utilization of steatotic livers. Here we review current knowledge on the mechanisms whereby excessive lipid storage and macrosteatosis exacerbate hepatic I/R injury, and possible approaches to address this problem, including ex vivo perfusion methods as well as metabolically induced defatting. We also discuss the challenges ahead that need to be addressed for clinical implementation.
大于 30%的肝细胞出现大泡性脂肪变性是原发性移植物无功能的一个重要危险因素，这是由于对缺血再灌注 (I/R) 损伤的敏感性增加所致。由于肥胖症的流行，肝脂肪变性的患病率不断增加，再加上人口老龄化，可能会对合适的已故肝脏供体的可用性产生负面影响。有人认为，在移植前进行代谢干预可能会降低肝移植物的脂肪含量。这一概念已在少数活体供者的营养补充中得到成功验证。然而，使用已故供体的肝脏需要对已取出的器官进行去脂。动物研究表明，通过几个小时的体外温热灌注可以达到这种效果。我们估计，通过增加对脂肪变性肝脏的利用，这种方法可以显著增加供体库的规模。在这里，我们回顾了关于过度脂质储存和大泡性脂肪变性加剧肝 I/R 损伤的机制的现有知识，以及解决这一问题的可能方法，包括体外灌注方法以及代谢诱导去脂。我们还讨论了为临床实施需要解决的未来挑战。
