Biliary Atresia - emerging diagnostic and therapy opportunities

Urban Lendahl, Vincent C H Lui, Patrick H Y Chung, Paul K H Tam, Urban Lendahl, Vincent C H Lui, Patrick H Y Chung, Paul K H Tam

Abstract

Biliary Atresia is a devastating pediatric cholangiopathy affecting the bile ducts of the liver. In this review, we describe recent progress in the understanding of liver development with a focus on cholangiocyte differentiation and how use of technical platforms, including rodent, zebrafish and organoid models, advances our understanding of Biliary Atresia. This is followed by a description of potential pathomechanisms, such as autoimmune responses, inflammation, disturbed apical-basal cell polarity, primary cilia dysfunction as well as beta-amyloid accumulation. Finally, we describe current and emerging diagnostic opportunities and recent translation breakthroughs for Biliary Atresia in the area of emerging therapy development, including immunomodulation and organoid-based systems for liver and bile duct repair.

Keywords: Biliary Atresia; Cholangiocyte; Cholangiopathy; Disease Models; Pathomechanisms; Therapy.

Conflict of interest statement

Declaration of Competing Interest The authors declare that they have no competing interests.

Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.

Figures

Fig. 1
Fig. 1
Schematic depiction of Biliary Atresia. Potential causes for BA are described, as well as the major pathological features of BA, including obstruction of the extrahepatic bile ducts and deterioration of intrahepatic bile ducts. The gallbladder (green) pancreas (beige) and duodenum (light pink) are also shown. Hematoxylin and eosin (H&E) stained and cytokeratin 19 (CK19)-immunostained liver sections from a BA patient and a non-BA control are displayed. At the bottom of the figure, the main topics of the review article are described.
Fig. 2
Fig. 2
Overview of the liver, with the extra- and intrahepatic bile ducts and their different developmental origins. The intrahepatic bile ducts and the cranial (proximal) common bile duct (shown in red) are derived from one portion of the liver bud (pars hepatica). The extrahepatic bile ducts, including the caudal (distal) common bile duct, as well as the gallbladder and cystic duct connecting the gallbladder to the common bile duct (shown in yellow), are derived from the pars cystica in the liver bud.

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