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Biliary Atresia and the Ductal Plate

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Fibrocystic Diseases of the Liver

Part of the book series: Clinical Gastroenterology ((CG))

Summary

Biliary atresia (BA) is a unique neonatal disease, presenting with complete obstruction of the extrahepatic biliary tree within the first 3 months of life. Current therapy requires a hepatic portoenterostomy within the first months of life; however, progressive intrahepatic bile duct injury, sclerosis, and obstruction lead to cirrhosis and the need for liver transplantation in the majority of patients. Medical treatments are inadequate largely because the pathogenesis of BA is poorly understood. Two major forms of BA have been described. The embryonic form is associated with other congenital malformations and presumably represents failure of normal bile duct formation. Mutations or epigenetic modifications in genes involving laterality and bile duct morphogenesis or ductal plate regression are proposed to be involved. The perinatal form is not associated with other malformations and is proposed to be caused by an immune or an autoimmune response to a perinatal insult (e.g., cholangiotropic viral infection). There is conflicting evidence for the role of several viruses, although the mouse rhesus rotavirus model of BA makes human rotavirus and reovirus intriguing candidates. Future investigations in coming years are anticipated to unlock the mysteries surrounding the etiology of BA with the promise of new therapeutic strategies and potential prevention.

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Abbreviations

APC:

antigen-presenting cell

BA:

biliary atresia

CD:

clusters of differentiation

CMV:

cytomegalovirus

HLA:

human leukocyte antigen

IFN:

interferon

IL:

interleukin

INV:

inversin

LBW:

low birth weight

MHC:

major histocompatibility complex

OR:

odds ratio

RNA:

ribonucleic acid

RR:

risk ratio

RT-PCR:

reverse transcriptase-polymerase chain reaction

SGA:

small for gestational age

TNF:

tumor necrosis factor

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Acknowledgment

Supported in part by grants from the National Institutes of Health (R01 DK38446, UO1 DK062453, U54 RR019455, M01 RR00069, and UL1RR025780) and the Abby Bennett Liver Research Fund.

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Authors and Affiliations

  1. Section of Pediatric Gastroenterology, Hepatology and Nutrition, Department of Pediatrics Colorado Clinical and Translational Sciences Institute, Pediatric Liver Center and Liver Transplantation Program, University of Colorado Denver School of Medicine and The Children’s Hospital, Aurora, CO, USA

    Ronald J. Sokol MD & Cara L. Mack MD

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  1. Ronald J. Sokol MD
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  1. School of Medicine, Children's Hospital & Regional, University of Washington, Sand Point Way NE. 4800, Seattle, 98105, USA

    Karen F. Murray

  2. St. Paul University Hospital, Harry Hines Blvd. 5939, Dallas, 75390-9258, USA

    Anne M. Larson

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Sokol, R.J., Mack, C.L. (2010). Biliary Atresia and the Ductal Plate. In: Murray, K., Larson, A. (eds) Fibrocystic Diseases of the Liver. Clinical Gastroenterology. Humana Press. https://doi.org/10.1007/978-1-60327-524-8_8

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