Skip to main content
Top
Published in: Digestive Diseases and Sciences 3/2017

01-03-2017 | Original Article

Peribiliary Gland Dilatation in Cirrhosis: Relationship with Liver Failure and Stem Cell/Proliferation Markers

Authors: Nicolas Goossens, Romain Breguet, Claudio De Vito, Sylvain Terraz, Nathalie Lin-Marq, Emiliano Giostra, Laura Rubbia-Brandt, Laurent Spahr

Published in: Digestive Diseases and Sciences | Issue 3/2017

Login to get access

Abstract

Background and Aims

Dilated peribiliary glands (PBG) in patients with cirrhosis are often an incidental finding although their significance and physiopathology remain unclear. We aimed to identify clinical factors associated with dilated PBG and to perform a detailed morphometric assessment of dilated PBG in cirrhotic patients undergoing liver transplantation (LT).

Methods

All consecutive cirrhotic patients undergoing LT at our institution between October 2006 and October 2011 were assessed for inclusion. Ten non-cirrhotic patients were included as controls. We performed morphometrical assessment of PBG, assessed baseline clinical factors associated with dilated PBG, immunohistochemistry staining with CK-19, MiB-1 and EpCAM, and radiological assessment of all available cases.

Results

Seventy-one patients met the inclusion criteria, 24% had PBG dilatation of >1000 µm. On multivariable analysis, MELD (OR 1.11 per unit increase in MELD, p = 0.004) was the only significant factor associated with dilated PBG. Compared to PBG < 1000 µm, large PBG had a higher proportion of EpCAM-positive (69 vs. 28%, p < 0.001) and MiB-1-positive lining cells (2.8 vs. 0.55%, p = 0.036). Computed tomography and magnetic resonance imaging had high specificity but low sensitivity for the diagnosis of dilated PBG > 1000 µm (specificity 90–100%, sensitivity 25–29%).

Conclusions

Dilated PBGs are a common finding in explants of cirrhotic subjects undergoing LT and are associated with liver failure although diagnostic performance of cross-sectional imaging is inconstant. The high number of proliferative and EpCAM-positive cells lining the PBG may suggest a role of PBG in organ repair during liver failure.
Appendix
Available only for authorised users
Literature
1.
go back to reference Nakanuma Y, Kurumaya H, Ohta G. Multiple cysts in the hepatic hilum and their pathogenesis. A suggestion of periductal gland origin. Virchows Arch A Pathol Anat Histopathol. 1984;404:341–350.CrossRefPubMed Nakanuma Y, Kurumaya H, Ohta G. Multiple cysts in the hepatic hilum and their pathogenesis. A suggestion of periductal gland origin. Virchows Arch A Pathol Anat Histopathol. 1984;404:341–350.CrossRefPubMed
2.
go back to reference Okada SI, Kojima Y, Morozumi A, Ainota T, Miyazaki Y, Akahane Y. Multiple hepatic peribiliary cysts discovered incidentally at a medical examination. J Gastroenterol Hepatol. 2001;16:1167–1169.CrossRefPubMed Okada SI, Kojima Y, Morozumi A, Ainota T, Miyazaki Y, Akahane Y. Multiple hepatic peribiliary cysts discovered incidentally at a medical examination. J Gastroenterol Hepatol. 2001;16:1167–1169.CrossRefPubMed
3.
go back to reference Nakanuma Y, Hoso M, Sanzen T, Sasaki M. Microstructure and development of the normal and pathologic biliary tract in humans, including blood supply. Microsc Res Tech. 1997;38:552–570.CrossRefPubMed Nakanuma Y, Hoso M, Sanzen T, Sasaki M. Microstructure and development of the normal and pathologic biliary tract in humans, including blood supply. Microsc Res Tech. 1997;38:552–570.CrossRefPubMed
4.
go back to reference Baron RL, Campbell WL, Dodd GD II. Peribiliary cysts associated with severe liver disease: imaging-pathologic correlation. Am J Roentgenol. 1994;162:631–636.CrossRef Baron RL, Campbell WL, Dodd GD II. Peribiliary cysts associated with severe liver disease: imaging-pathologic correlation. Am J Roentgenol. 1994;162:631–636.CrossRef
5.
go back to reference Kai K, Eguchi Y, Kumagai T, Sugita Y, Tokunaga O. An autopsy case of obstructive jaundice due to hepatic multiple peribiliary cysts accompanying hepatolithiasis. Hepatol Res. 2008;38:211–216.CrossRefPubMed Kai K, Eguchi Y, Kumagai T, Sugita Y, Tokunaga O. An autopsy case of obstructive jaundice due to hepatic multiple peribiliary cysts accompanying hepatolithiasis. Hepatol Res. 2008;38:211–216.CrossRefPubMed
6.
go back to reference Wanless IR, Zahradnik J, Heathcote EJ. Hepatic cysts of periductal gland origin presenting as obstructive jaundice. Gastroenterology. 1987;93:894–898.CrossRefPubMed Wanless IR, Zahradnik J, Heathcote EJ. Hepatic cysts of periductal gland origin presenting as obstructive jaundice. Gastroenterology. 1987;93:894–898.CrossRefPubMed
7.
go back to reference Terada T, Nakanuma Y. Pathological observations of intrahepatic peribiliary glands in 1000 consecutive autopsy livers. III. Survey of necroinflammation and cystic dilatation. Hepatology. 1990;12:1229–1233.CrossRefPubMed Terada T, Nakanuma Y. Pathological observations of intrahepatic peribiliary glands in 1000 consecutive autopsy livers. III. Survey of necroinflammation and cystic dilatation. Hepatology. 1990;12:1229–1233.CrossRefPubMed
8.
go back to reference Hoshiba K, Matsui O, Kadoya M, et al. Peribiliary cysts in cirrhotic liver: observation on computed tomography. Abdom Imaging. 1996;21:228–232.CrossRefPubMed Hoshiba K, Matsui O, Kadoya M, et al. Peribiliary cysts in cirrhotic liver: observation on computed tomography. Abdom Imaging. 1996;21:228–232.CrossRefPubMed
9.
go back to reference Cardinale V, Wang Y, Carpino G, et al. Multipotent stem/progenitor cells in human biliary tree give rise to hepatocytes, cholangiocytes, and pancreatic islets. Hepatology. 2011;54:2159–2172.CrossRefPubMed Cardinale V, Wang Y, Carpino G, et al. Multipotent stem/progenitor cells in human biliary tree give rise to hepatocytes, cholangiocytes, and pancreatic islets. Hepatology. 2011;54:2159–2172.CrossRefPubMed
10.
go back to reference Carpino G, Cardinale V, Onori P, et al. Biliary tree stem/progenitor cells in glands of extrahepatic and intraheptic bile ducts: an anatomical in situ study yielding evidence of maturational lineages. J Anat. 2012;220:186–199.CrossRefPubMed Carpino G, Cardinale V, Onori P, et al. Biliary tree stem/progenitor cells in glands of extrahepatic and intraheptic bile ducts: an anatomical in situ study yielding evidence of maturational lineages. J Anat. 2012;220:186–199.CrossRefPubMed
11.
go back to reference Igarashi S, Sato Y, Ren XS, Harada K, Sasaki M, Nakanuma Y. Participation of peribiliary glands in biliary tract pathophysiologies. World J Hepatol. 2013;5:425–432.CrossRefPubMedPubMedCentral Igarashi S, Sato Y, Ren XS, Harada K, Sasaki M, Nakanuma Y. Participation of peribiliary glands in biliary tract pathophysiologies. World J Hepatol. 2013;5:425–432.CrossRefPubMedPubMedCentral
12.
go back to reference DiPaola F, Shivakumar P, Pfister J, Walters S, Sabla G, Bezerra JA. Identification of intramural epithelial networks linked to peribiliary glands that express progenitor cell markers and proliferate after injury in mice. Hepatology. 2013;58:1486–1496.CrossRefPubMedPubMedCentral DiPaola F, Shivakumar P, Pfister J, Walters S, Sabla G, Bezerra JA. Identification of intramural epithelial networks linked to peribiliary glands that express progenitor cell markers and proliferate after injury in mice. Hepatology. 2013;58:1486–1496.CrossRefPubMedPubMedCentral
13.
go back to reference Lanthier N, Rubbia-Brandt L, Lin-Marq N, et al. Hepatic cell proliferation plays a pivotal role in the prognosis of alcoholic hepatitis. J Hepatol. 2015;63:609–621.CrossRefPubMed Lanthier N, Rubbia-Brandt L, Lin-Marq N, et al. Hepatic cell proliferation plays a pivotal role in the prognosis of alcoholic hepatitis. J Hepatol. 2015;63:609–621.CrossRefPubMed
14.
go back to reference Carpino G, Cardinale V, Gentile R, et al. Evidence for multipotent endodermal stem/progenitor cell populations in human gallbladder. J Hepatol. 2014;60:1194–1202.CrossRefPubMed Carpino G, Cardinale V, Gentile R, et al. Evidence for multipotent endodermal stem/progenitor cell populations in human gallbladder. J Hepatol. 2014;60:1194–1202.CrossRefPubMed
15.
go back to reference Yoon SM, Gerasimidou D, Kuwahara R, et al. Epithelial cell adhesion molecule (EpCAM) marks hepatocytes newly derived from stem/progenitor cells in humans. Hepatology. 2011;53:964–973.CrossRefPubMed Yoon SM, Gerasimidou D, Kuwahara R, et al. Epithelial cell adhesion molecule (EpCAM) marks hepatocytes newly derived from stem/progenitor cells in humans. Hepatology. 2011;53:964–973.CrossRefPubMed
16.
go back to reference Farinati F, Cardin R, D’Errico A, et al. Hepatocyte proliferative activity in chronic liver damage as assessed by the monoclonal antibody MIB1 Ki67 in archival material: the role of etiology, disease activity, iron, and lipid peroxidation. Hepatology. 1996;23:1468–1475.CrossRefPubMed Farinati F, Cardin R, D’Errico A, et al. Hepatocyte proliferative activity in chronic liver damage as assessed by the monoclonal antibody MIB1 Ki67 in archival material: the role of etiology, disease activity, iron, and lipid peroxidation. Hepatology. 1996;23:1468–1475.CrossRefPubMed
17.
go back to reference Matsubara T, Sato Y, Igarashi S, Matsui O, Gabata T, Nakanuma Y. Alcohol-related injury to peribiliary glands is a cause of peribiliary cysts: based on analysis of clinical and autopsy cases. J Clin Gastroenterol. 2014;48:153–159.CrossRefPubMed Matsubara T, Sato Y, Igarashi S, Matsui O, Gabata T, Nakanuma Y. Alcohol-related injury to peribiliary glands is a cause of peribiliary cysts: based on analysis of clinical and autopsy cases. J Clin Gastroenterol. 2014;48:153–159.CrossRefPubMed
18.
go back to reference Kai K, Takahashi T, Miyoshi A, Yasui T, Tokunaga O, Miyazaki K. Intrahepatic multicystic biliary hamartoma: report of a case. Hepatol Res. 2008;38:629–634.CrossRefPubMed Kai K, Takahashi T, Miyoshi A, Yasui T, Tokunaga O, Miyazaki K. Intrahepatic multicystic biliary hamartoma: report of a case. Hepatol Res. 2008;38:629–634.CrossRefPubMed
19.
go back to reference Seguchi T, Akiyama Y, Itoh H, et al. Multiple hepatic peribiliary cysts with cirrhosis. J Gastroenterol. 2004;39:384–390.CrossRefPubMed Seguchi T, Akiyama Y, Itoh H, et al. Multiple hepatic peribiliary cysts with cirrhosis. J Gastroenterol. 2004;39:384–390.CrossRefPubMed
20.
go back to reference Cardinale V, Wang Y, Carpino G, et al. The biliary tree—a reservoir of multipotent stem cells. Nat Rev Gastroenterol Hepatol. 2012;9:231–240.CrossRefPubMed Cardinale V, Wang Y, Carpino G, et al. The biliary tree—a reservoir of multipotent stem cells. Nat Rev Gastroenterol Hepatol. 2012;9:231–240.CrossRefPubMed
21.
go back to reference Semeraro R, Carpino G, Cardinale V, et al. Multipotent stem/progenitor cells in the human foetal biliary tree. J Hepatol. 2012;57:987–994.CrossRefPubMed Semeraro R, Carpino G, Cardinale V, et al. Multipotent stem/progenitor cells in the human foetal biliary tree. J Hepatol. 2012;57:987–994.CrossRefPubMed
22.
go back to reference Op den Dries S, Westerkamp AC, Karimian N, et al. Injury to peribiliary glands and vascular plexus before liver transplantation predicts formation of non-anastomotic biliary strictures. J Hepatol. 2014;60:1172–1179.CrossRefPubMed Op den Dries S, Westerkamp AC, Karimian N, et al. Injury to peribiliary glands and vascular plexus before liver transplantation predicts formation of non-anastomotic biliary strictures. J Hepatol. 2014;60:1172–1179.CrossRefPubMed
23.
go back to reference Carpino G, Cardinale V, Renzi A, et al. Activation of biliary tree stem cells within peribiliary glands in primary sclerosing cholangitis. J Hepatol. 2015;63:1220–1228.CrossRefPubMed Carpino G, Cardinale V, Renzi A, et al. Activation of biliary tree stem cells within peribiliary glands in primary sclerosing cholangitis. J Hepatol. 2015;63:1220–1228.CrossRefPubMed
24.
go back to reference Sutton ME, Dries S, Koster MH, Lisman T, Gouw ASH, Porte RJ. Regeneration of human extrahepatic biliary epithelium: the peribiliary glands as progenitor cell compartment. Liver Int. 2012;32:554–559.CrossRefPubMed Sutton ME, Dries S, Koster MH, Lisman T, Gouw ASH, Porte RJ. Regeneration of human extrahepatic biliary epithelium: the peribiliary glands as progenitor cell compartment. Liver Int. 2012;32:554–559.CrossRefPubMed
25.
go back to reference Jain R, Fischer S, Serra S, Chetty R. The use of Cytokeratin 19 (CK19) immunohistochemistry in lesions of the pancreas, gastrointestinal tract, and liver. Appl Immunohistochem Mol Morphol. 2010;18:9–15.CrossRefPubMed Jain R, Fischer S, Serra S, Chetty R. The use of Cytokeratin 19 (CK19) immunohistochemistry in lesions of the pancreas, gastrointestinal tract, and liver. Appl Immunohistochem Mol Morphol. 2010;18:9–15.CrossRefPubMed
26.
go back to reference Trzpis M, McLaughlin PM, de Leij LM, Harmsen MC. Epithelial cell adhesion molecule: more than a carcinoma marker and adhesion molecule. Am J Pathol. 2007;171:386–395.CrossRefPubMedPubMedCentral Trzpis M, McLaughlin PM, de Leij LM, Harmsen MC. Epithelial cell adhesion molecule: more than a carcinoma marker and adhesion molecule. Am J Pathol. 2007;171:386–395.CrossRefPubMedPubMedCentral
Metadata
Title
Peribiliary Gland Dilatation in Cirrhosis: Relationship with Liver Failure and Stem Cell/Proliferation Markers
Authors
Nicolas Goossens
Romain Breguet
Claudio De Vito
Sylvain Terraz
Nathalie Lin-Marq
Emiliano Giostra
Laura Rubbia-Brandt
Laurent Spahr
Publication date
01-03-2017
Publisher
Springer US
Published in
Digestive Diseases and Sciences / Issue 3/2017
Print ISSN: 0163-2116
Electronic ISSN: 1573-2568
DOI
https://doi.org/10.1007/s10620-016-4421-x

Other articles of this Issue 3/2017

Digestive Diseases and Sciences 3/2017 Go to the issue
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discuss last year's major advances in heart failure and cardiomyopathies.