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Extrahepatic Cholangiocyte Cilia Are Abnormal in Biliary Atresia

Karjoo, Sara*; Hand, Nicholas J.*; Loarca, Lorena; Russo, Pierre A.; Friedman, Joshua R.*; Wells, Rebecca G.

Journal of Pediatric Gastroenterology and Nutrition: July 2013 - Volume 57 - Issue 1 - p 96–101
doi: 10.1097/MPG.0b013e318296e525
Original Articles: Hepatology and Nutrition

Objectives: Biliary atresia (BA) is a rapidly progressive form of biliary fibrosis affecting neonates. We previously reported that primary cilia on the intrahepatic cholangiocytes of patients with both syndromic and nonsyndromic BA were structurally abnormal. Our objective was to determine whether extrahepatic cholangiocytes in human biliary atesia, intrahepatic and extrahepatic cholangiocytes of rhesus rotavirus (RRV)-infected neonatal mice, and RRV-infected primary neonatal extrahepatic cholangiocytes also demonstrate ciliary abnormalities.

Methods: The livers of neonatal BALB/c mice injected with RRV that developed jaundice, human extrahepatic bile duct samples obtained at time of hepatoportoenterostomy, and RRV-infected primary neonatal cholangiocytes were stained with antibodies against acetylated α tubulin to identify primary cilia.

Results: Extrahepatic cholangiocytes from RRV-treated mice demonstrated minimal loss of primary cilia at day 3 but almost complete loss at day 8 and partial loss at day 12. No changes were seen in mouse intrahepatic bile ducts at any of the time points. In the human BA samples, primary cilia were almost completely absent from extrahepatic duct cholangiocytes. There were, however, abundant cilia in the peribiliary glands adjacent to extrahepatic ducts in the BA sample. Cilia in RRV-infected primary neonatal cholangiocytes were significantly decreased compared with controls.

Conclusions: Primary cilia are selectively lost from neonatal extrahepatic but not intrahepatic cholangiocytes after RRV infection in BALB/c mice. The cilia are also decreased in RRV-infected primary cholangiocytes and the extrahepatic ducts from human patients with BA. This suggests that ciliary abnormalities are part of the pathophysiology of BA.

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*Division of Gastroenterology, Hepatology, and Nutrition

Division of Anatomic Pathology, The Children's Hospital of Philadelphia

Department of Medicine, Division of Gastroenterology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA.

Address correspondence and reprint requests to Rebecca G. Wells, MD, 905 BRB II/III, Department of Medicine (Gastroenterology), University of Pennsylvania School of Medicine, 421 Curie Boulevard, Philadelphia, PA 19104-6160 (e-mail:

Received 8 March, 2013

Accepted 12 April, 2013

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Website (

This work was supported by grants from the Fred and Suzanne Biesecker Pediatric Liver Center (to R.G.W. and J.R.F.) and by a fellowship from the Childhood Liver Disease Research and Education Network (to S.K.). J.R.F. was supported by R01-DK079881.

The authors report no conflicts of interest.

© 2013 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology,