Intra-Hepatic Bile Duct Primary Cilia In Biliary Atresia

• Published in: Hepatology research
• Main Authors: Frassetto, Roberta, Parolini, Filippo, Marceddu, Salvatore, Satta, Giulia, Papacciuoli, Valeria, Pinna, Maria Antonia, Mela, Alessandra, Secchi, Giannina, Galleri, Grazia, Manetti, Roberto, Bercich, Luisa, Villanacci, Vincenzo, Dessanti, Antonio, Antonucci, Roberto, Tanda, Francesco, Alberti, Daniele, Schwarz, Kathleen B, Clemente, Maria Grazia
• Format: Journal Article
• Language: English
• Published: Netherlands 13-01-2018
• Subjects: scanning electron microscopy; liver fibrosis; biliary disease; choledochal cyst; liver transplantation
• ISSN: 1386-6346

The etiopathogenesis of non-syndromic biliary atresia (BA) is obscure. The primary aim was to investigate intra-hepatic bile duct cilia (IHBC) in BA at the diagnosis and correlation with clinical outcome. The secondary aim was to analyze IHBC in routine paraffin-embedded liver biopsies using conventional scanning electron microscopy (SEM).
Surgical liver biopsies taken at the diagnosis from 22 BA infants (age range: 39 - 116 days) and from 8 children with non-BA chronic cholestasis (age range: 162 days -16,8 years) were evaluated for IHBC, both by immunofluorescence (IF) and by SEM. A minimum 18 -month-follow-up after surgery was available for all patients.
By IF, cilia were present in 6/8 (75%) non-BA but only in 3/22 (14%) BA, while cilia were reduced or absent in 19/22 (86%) BA and 2/8 (25%) non-BA livers (p<0.01). In BA, cilia presence was found associated with clearance of jaundice at 6-month-follow-up (p<0.05). However, high overall survival rates with native liver, >90% at 12 months and >70% at 24 months post-surgery, were recorded regardless of cilia presence/absence at the diagnosis. Electron microscopy was able to detect bile ducts and cilia in routine liver biopsies, revealing significant abnormalities in 100% BA livers.
The presence of IHBC in BA livers at the diagnosis was associated with resolution of cholestasis although was not predictive of short-term survival with native liver. SEM represents a powerful new tool to study routine liver biopsies in biliary disorders. Cilia dysfunction in BA pathogenesis and/or disease progression warrants further investigation.