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.

中文翻译：

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长期异位常温机器灌注可实现严重胆管损伤的人类肝脏再生


胆管再生被假设可以预防胆道狭窄，胆道狭窄是肝移植后发病的主要原因。评估胆道再生能力可能会确定目前拒绝移植的移植物适合移植，但直到现在这都是不可行的。本研究使用长期异位常温机器灌注 （LT-NMP） 来评估胆道再生。拒绝移植的人肝脏在 36 °C 下灌注长达 13.5 天。在整个灌注过程中收集胆管活检、胆汁和灌注液，检查损伤和再生特征。胆汁再生被定义为严重损伤后新的 Ki-67 阳性胆汁上皮。10 个肝脏灌注，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% 的移植物发生胆道再生。传统的胆汁活力生物标志物，如胆汁葡萄糖，在灌注过程中得到改善，但这与胆道再生无关 （P > .05）。相比之下，胆汁中白细胞介素 6 和血管内皮生长因子 A 水平的维持与胆道再生相关 （两种细胞因子的 P = .017）。这是第一项证明 LT-NMP 期间胆汁再生的研究，并将胆汁中的细胞因子特征确定为 LT-NMP 期间胆汁再生的新型生物标志物。