Liver Transplant Unit, Department of Surgery, Hospital Clinic, University of Barcelona, C/Villarroel 170, 08036 Barcelona, Spain.
Liver Transpl. 2010 Mar;16(3):364-74. doi: 10.1002/lt.21989.
Understanding the pathogenesis of small-for-size (SFS) syndrome is critical to expanding the applicability of partial liver transplantation. We aimed to characterize its acute presentation and association with alterations in hepatic hemodynamics, microstructure, and regeneration in a porcine model. Eighteen SFS liver transplants were performed. Donors underwent 70% hepatectomy. Partial grafts were implanted into larger recipients. Whole liver transplants were also performed (n = 6). Recipients were followed until death or for 5 days. Hemodynamics were measured, and tissue was sampled intraoperatively and at the study end. Serum was sampled regularly during follow-up. Seventeen SFS transplants and 6 whole liver transplants were included. SFS grafts represented 23.2% (19.3%-25.3%) of the recipients' standard liver volume. The survival rate was 29% and 100% in the SFS and whole liver groups, respectively. The portal venous flow, pressure gradient, and resistance were significantly higher in recipients of SFS grafts versus whole livers after portal and arterial reperfusion. Arterial flow as a percentage of the total liver blood flow was significantly lower after reperfusion in SFS grafts and remained so when measured again after 5 days. Markers of endothelial cell injury increased soon after reperfusion, and those of hepatocellular injury increased later; both predicted the appearance of either graft failure or histological recovery. Proliferative activity peaked earlier and higher among nonsurvivors in the SFS group. Surviving grafts demonstrated a slower but maintained rise in regenerative activity, although metabolic activity failed to improve. In SFS transplantation in the acute setting, portal hyperperfusion is a stimulus for regeneration but may simultaneously cause irreparable endothelial injury. This porcine model not only helps to elucidate the inciting factors in SFS pathogenesis but also offers a clinically relevant means to study its prevention.
了解小肝综合征(SFS)的发病机制对于扩大部分肝移植的适用性至关重要。我们旨在描述其急性表现,并探讨其与肝血流动力学、微观结构和再生改变的关系,为此建立了一个猪模型。在该模型中,进行了 18 例 SFS 肝移植手术。供体接受 70%的肝切除术。部分移植物被植入较大的受体中。同时还进行了全肝移植(n=6)。受体在死亡或 5 天内被随访。术中及研究结束时测量血流动力学,同时采集组织样本。在随访期间定期采集血清样本。纳入了 17 例 SFS 移植和 6 例全肝移植。SFS 移植物代表受体标准肝体积的 23.2%(19.3%-25.3%)。SFS 组和全肝组的存活率分别为 29%和 100%。门静脉和动脉再灌注后,SFS 移植受体的门静脉血流、压力梯度和阻力明显高于全肝受体。再灌注后,SFS 移植物的动脉血流占总肝血流的百分比明显降低,5 天后再次测量时仍如此。再灌注后不久,内皮细胞损伤标志物增加,肝细胞损伤标志物增加较晚;两者均预测移植物失功或组织学恢复。SFS 组非幸存者的增殖活性更早且更高。存活的移植物表现出较慢但持续的再生活性升高,尽管代谢活性未能改善。在急性 SFS 移植中,门静脉高灌注是再生的刺激因素,但同时可能导致不可逆转的内皮损伤。该猪模型不仅有助于阐明 SFS 发病机制中的激发因素,还为研究其预防提供了一种临床相关的方法。