Ly Mark, Lau Ngee-Soon, Dennis Claude, Chen Jinbiao, Risbey Charles, Tan Sarah, Chen Renfen, Wang Chuanmin, Gorrell Mark D, McKenzie Catriona, Kench James G, Liu Ken, McCaughan Geoffrey W, Crawford Michael, Pulitano Carlo
Centre for Organ Assessment Repair and Optimisation, Royal Prince Alfred Hospital, Sydney, Australia; Australian National Liver Transplantation Unit, Royal Prince Alfred Hospital, Sydney, Australia; Centenary Institute, The University of Sydney, Sydney, Australia; Faculty of Medicine and Health, The University of Sydney, Sydney, Australia.
Centre for Organ Assessment Repair and Optimisation, Royal Prince Alfred Hospital, Sydney, Australia; Australian National Liver Transplantation Unit, Royal Prince Alfred Hospital, Sydney, Australia; Faculty of Medicine and Health, The University of Sydney, Sydney, Australia.
Am J Transplant. 2025 Jan;25(1):60-71. doi: 10.1016/j.ajt.2024.07.019. Epub 2024 Jul 24.
Bile duct regeneration is hypothesized to prevent biliary strictures, a leading cause of morbidity after liver transplantation. Assessing the capacity for biliary regeneration may identify grafts as suitable for transplantation that are currently declined, but this has been unfeasible until now. This study used long-term ex situ normothermic machine perfusion (LT-NMP) to assess biliary regeneration. Human livers that were declined for transplantation were perfused at 36 °C for up to 13.5 days. Bile duct biopsies, bile, and perfusate were collected throughout perfusion, which were examined for features of injury and regeneration. Biliary regeneration was defined as new Ki-67-positive biliary epithelium following severe injury. Ten livers were perfused for a median duration of 7.5 days. Severe bile duct injury occurred in all grafts, and biliary regeneration occurred in 70% of grafts. Traditional biomarkers of biliary viability such as bile glucose improved during perfusion but this was not associated with biliary regeneration (P > .05). In contrast, the maintenance of interleukin-6 and vascular endothelial growth factor-A levels in bile was associated with biliary regeneration (P = .017 for both cytokines). This is the first study to demonstrate biliary regeneration during LT-NMP and identify a cytokine signature in bile as a novel biomarker for biliary regeneration during LT-NMP.
胆管再生被认为可以预防胆管狭窄，而胆管狭窄是肝移植后发病的主要原因。评估胆管再生能力可能会识别出目前被拒绝但适合移植的移植物，但到目前为止这一直不可行。本研究采用长期体外常温机器灌注（LT-NMP）来评估胆管再生。将被拒绝移植的人类肝脏在36℃下灌注长达13.5天。在整个灌注过程中收集胆管活检组织、胆汁和灌注液，检查其损伤和再生特征。胆管再生定义为严重损伤后新的Ki-67阳性胆管上皮。10个肝脏被灌注，中位持续时间为7.5天。所有移植物均发生严重胆管损伤，70%的移植物发生胆管再生。胆管活力的传统生物标志物如胆汁葡萄糖在灌注过程中有所改善，但这与胆管再生无关（P>.05）。相反，胆汁中白细胞介素-6和血管内皮生长因子-A水平的维持与胆管再生相关（两种细胞因子的P值均为0.017）。这是第一项证明LT-NMP期间胆管再生并确定胆汁中的细胞因子特征作为LT-NMP期间胆管再生新生物标志物的研究。
