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Biliary Atresia Remnants Revisited: Myogenesis, Hepatic Duct-Like Structures, and Fate of Peribiliary Glands

Kevin E Bove1, Milton J Finegold2, Sanjiv Harpavat3

  • 1Department of Pathology, University of Cincinnati College of Medicine, Cincinnati, OH, USA.

Pediatric and Developmental Pathology : the Official Journal of the Society for Pediatric Pathology and the Paediatric Pathology Society
|February 27, 2023
PubMed

Insights

Early biliary atresia (BA) features are identified in infant remnants using reactive myogenesis (RM). This study defines three novel hepatic duct remnants (HDR) and highlights RM as a key indicator in diagnosing BA.

Area of Science:

  • Pediatric pathology
  • Gastroenterology
  • Developmental biology

Background:

  • Biliary atresia (BA) is a neonatal cholestatic disease with unknown etiology.
  • Early diagnosis of BA is crucial for effective treatment and improved outcomes.
  • Proximal remnants of excised biliary structures may offer insights into early BA pathogenesis.

Purpose of the Study:

  • To investigate early features of biliary atresia (BA) in proximal remnants from infants.
  • To identify novel histological markers and structures within BA remnants.
  • To assess the role of reactive myogenesis (RM) in the context of BA.

Main Methods:

  • Immunohistochemical (IHC) analysis of 17 BA remnants from infants aged 10-74 days.
  • Comparison of proximal remnant tissue with 6 control hepatic ducts (HD).
  • Evaluation of inflammation, fibroplasia, and the presence of smooth muscle myosin (SM-MHC-2) to identify reactive myogenesis (RM).

Main Results:

  • Reactive myogenesis (RM), marked by SM-MHC-2, was identified in 14/17 BA remnants but absent in controls.
  • RM was associated with three novel hepatic duct remnants (HDR): collagen collar, erosion defects, and hyperplastic squamoid epithelium.
  • Inflammation and fibroplasia severity did not differentiate younger from older infants, suggesting early onset BA.

Conclusions:

  • Minimally inflamed lesions in BA remnants at the youngest ages suggest a prenatal onset.
  • Three novel hepatic duct remnants (HDR) were defined, aiding in BA diagnosis.
  • Reactive myogenesis (RM) serves as a valuable surrogate marker for HDR and is the source of smooth muscle in BA remnants.
Abstract

Keywords:
biliary atresiacholangiocyte regressionenteric actinexcised remnantshepatic duct remnantsimmunohistochemistrymyogenic biliary stromaneonatal periodperibiliary gland atresiaperibiliary gland hyperplasia

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