Department of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Center for Engineering MechanoBiology, University of Pennsylvania, Philadelphia, PA, USA.
Pediatr Dev Pathol. 2024 Jul-Aug;27(4):291-310. doi: 10.1177/10935266241247479. Epub 2024 May 19.
Biliary atresia (BA) is a cholangiopathy affecting the extrahepatic bile duct (EHBD) of newborns. The etiology and pathophysiology of BA are not fully understood; however, multiple causes of damage and obstruction of the neonatal EHBD have been identified. Initial damage to the EHBD likely occurs before birth. We discuss how different developmental stages in utero and birth itself could influence the susceptibility of the fetal EHBD to damage and a damaging wound-healing response. We propose that a damage-repair response of the fetal and neonatal EHBD involving redox stress and a program of fetal wound healing could-regardless of the cause of the initial damage-lead to either obstruction and BA or repair of the duct and recovery. This overarching concept should guide future research targeted toward identification of factors that contribute to recovery as opposed to progression of injury and fibrosis. Viewing BA through the lens of an in utero damage-repair response could open up new avenues for research and suggests exciting new therapeutic targets.
先天性胆道闭锁（BA）是一种影响新生儿肝外胆管（EHBD）的胆管病。BA 的病因和病理生理学尚未完全阐明；然而，已经确定了新生儿 EHBD 损伤和阻塞的多种原因。EHBD 的初始损伤可能发生在出生前。我们讨论了宫内不同的发育阶段和出生本身如何影响胎儿 EHBD 对损伤和破坏性愈合反应的易感性。我们提出，胎儿和新生儿 EHBD 的损伤-修复反应涉及氧化应激和胎儿伤口愈合程序，无论初始损伤的原因如何，都可能导致胆管阻塞和 BA，或导管修复和恢复。这一总体概念应该指导未来的研究，以确定导致恢复的因素，而不是损伤和纤维化的进展。通过宫内损伤-修复反应的视角来看待 BA，可以为研究开辟新途径，并提出令人兴奋的新治疗靶点。
