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Semin Liver Dis 2023; 43(03): 323-335
DOI: 10.1055/a-2153-8927
Review Article

Genetic Contributions to Biliary Atresia: A Developmental Cholangiopathy

Dominick J. Hellen 
1   Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Children's Healthcare of Atlanta and Emory University School of Medicine, Atlanta, Georgia
,
Saul J. Karpen 
1   Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Children's Healthcare of Atlanta and Emory University School of Medicine, Atlanta, Georgia
› Author Affiliations Funding D.J.H. received financial support from NIH under ID T32GM008490 and F31DK137565. S.J.K. received funding from Mason Trust, under ID NIH R01DK135815.
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Erratum to: Genetic Contributions to Biliary Atresia: A Developmental CholangiopathySemin Liver Dis 2023; 43(03): e2-e2
DOI: 10.1055/s-0043-1776036

Abstract

Biliary atresia (BA) is the most prevalent serious liver disease of infancy and childhood, and the principal indication for liver transplantation in pediatrics. BA is best considered as an idiopathic panbiliary cholangiopathy characterized by obstruction of bile flow and consequent cholestasis presenting during fetal and perinatal periods. While several etiologies have been proposed, each has significant drawbacks that have limited understanding of disease progression and the development of effective treatments. Recently, modern genetic analyses have uncovered gene variants contributing to BA, thereby shifting the paradigm for explaining the BA phenotype from an acquired etiology (e.g., virus, toxin) to one that results from genetically altered cholangiocyte development and function. Herein we review recently reported genetic contributions to BA, highlighting the enhanced representation of variants in biological pathways involving ciliary function, cytoskeletal structure, and inflammation. Finally, we blend these findings as a new framework for understanding the resultant BA phenotype as a developmental cholangiopathy.

Keywords

epigenetics - cilia - cholangiocyte - mutation - cholestasis


Publication History

Accepted Manuscript online:
15 August 2023

Article published online:
19 September 2023

© 2023. Thieme. All rights reserved.

Thieme Medical Publishers, Inc.
333 Seventh Avenue, 18th Floor, New York, NY 10001, USA

 

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