Advanced search
1 file | 1.11 MB Add to list

Peripheral bile duct paucity and cholestasis in the liver of a patient with Alagille syndrome: further evidence supporting a lack of postnatal bile duct branching and elongation

Author
Organization
Abstract
Alagille syndrome (AGS) is a developmental, multiorgan disease caused by mutations of the Jagged1 gene. The liver is one of the major organs affected in AGS, and the hallmark of liver pathology in AGS is an age-related increase in the proportion of portal tracts that have no bile duct, but without evidence of prominent bile duct damage. The pathogenesis of this bile duct paucity is currently not well understood. (Immuno)histochemical and molecular analyses were performed on several liver biopsies that were taken during macroscopic examination of the explant liver of a 17-year-old AGS patient. The liver periphery was macroscopically pale and was microscopically characterized by complete absence of bile ducts and presence of severe cholestasis, but there was no ductular reaction. Conversely, the central, hilar portion contained normally developed bile ducts showing no or minimal damage and cholestasis. A missense mutation in the Jagged1 gene was present in both parts of the liver, indicating that mosaicism did not cause this peculiar picture. There was also a hypertrophy of the hepatic arterial branches in the liver periphery. Together with previous indirect findings, the current study of the explant liver of an AGS patient strongly suggests that a lack of branching and elongation of bile ducts during postnatal liver growth is the mechanism by which peripheral bile duct paucity and cholestasis develops in AGS. Our findings also suggest that anomalies of the intrahepatic arterial branches may be part of AGS in some patients.
Keywords
bile duct paucity, Alagille syndrome, bile duct development, Jagged1 gene, liver transplantation, PRIMARY BILIARY-CIRRHOSIS, ARTERIOHEPATIC DYSPLASIA, JAG1 MUTATIONS, HUMAN JAGGED1, EXPRESSION, TRANSPLANTATION, CYTOKERATIN-7, MORPHOGENESIS, HYPERPLASIA, FREQUENCY

Downloads

  • (...).pdf
    • full text
    • |
    • UGent only
    • |
    • PDF
    • |
    • 1.11 MB

Citation

Please use this url to cite or link to this publication:

MLA
Libbrecht, Louis, Nancy B Spinner, Elizabeth C Moore, et al. “Peripheral Bile Duct Paucity and Cholestasis in the Liver of a Patient with Alagille Syndrome: Further Evidence Supporting a Lack of Postnatal Bile Duct Branching and Elongation.” AMERICAN JOURNAL OF SURGICAL PATHOLOGY 29.6 (2005): 820–826. Print.
APA
Libbrecht, L., Spinner, N. B., Moore, E. C., Cassiman, D., Van Damme-Lombaerts, R., & Roskams, T. (2005). Peripheral bile duct paucity and cholestasis in the liver of a patient with Alagille syndrome: further evidence supporting a lack of postnatal bile duct branching and elongation. AMERICAN JOURNAL OF SURGICAL PATHOLOGY, 29(6), 820–826.
Chicago author-date
Libbrecht, Louis, Nancy B Spinner, Elizabeth C Moore, David Cassiman, Rita Van Damme-Lombaerts, and Tania Roskams. 2005. “Peripheral Bile Duct Paucity and Cholestasis in the Liver of a Patient with Alagille Syndrome: Further Evidence Supporting a Lack of Postnatal Bile Duct Branching and Elongation.” American Journal of Surgical Pathology 29 (6): 820–826.
Chicago author-date (all authors)
Libbrecht, Louis, Nancy B Spinner, Elizabeth C Moore, David Cassiman, Rita Van Damme-Lombaerts, and Tania Roskams. 2005. “Peripheral Bile Duct Paucity and Cholestasis in the Liver of a Patient with Alagille Syndrome: Further Evidence Supporting a Lack of Postnatal Bile Duct Branching and Elongation.” American Journal of Surgical Pathology 29 (6): 820–826.
Vancouver
1.
Libbrecht L, Spinner NB, Moore EC, Cassiman D, Van Damme-Lombaerts R, Roskams T. Peripheral bile duct paucity and cholestasis in the liver of a patient with Alagille syndrome: further evidence supporting a lack of postnatal bile duct branching and elongation. AMERICAN JOURNAL OF SURGICAL PATHOLOGY. 2005;29(6):820–6.
IEEE
[1]
L. Libbrecht, N. B. Spinner, E. C. Moore, D. Cassiman, R. Van Damme-Lombaerts, and T. Roskams, “Peripheral bile duct paucity and cholestasis in the liver of a patient with Alagille syndrome: further evidence supporting a lack of postnatal bile duct branching and elongation,” AMERICAN JOURNAL OF SURGICAL PATHOLOGY, vol. 29, no. 6, pp. 820–826, 2005.
@article{3183422,
  abstract     = {Alagille syndrome (AGS) is a developmental, multiorgan disease caused by mutations of the Jagged1 gene. The liver is one of the major organs affected in AGS, and the hallmark of liver pathology in AGS is an age-related increase in the proportion of portal tracts that have no bile duct, but without evidence of prominent bile duct damage. The pathogenesis of this bile duct paucity is currently not well understood. (Immuno)histochemical and molecular analyses were performed on several liver biopsies that were taken during macroscopic examination of the explant liver of a 17-year-old AGS patient. The liver periphery was macroscopically pale and was microscopically characterized by complete absence of bile ducts and presence of severe cholestasis, but there was no ductular reaction. Conversely, the central, hilar portion contained normally developed bile ducts showing no or minimal damage and cholestasis. A missense mutation in the Jagged1 gene was present in both parts of the liver, indicating that mosaicism did not cause this peculiar picture. There was also a hypertrophy of the hepatic arterial branches in the liver periphery. Together with previous indirect findings, the current study of the explant liver of an AGS patient strongly suggests that a lack of branching and elongation of bile ducts during postnatal liver growth is the mechanism by which peripheral bile duct paucity and cholestasis develops in AGS. Our findings also suggest that anomalies of the intrahepatic arterial branches may be part of AGS in some patients.},
  author       = {Libbrecht, Louis and Spinner, Nancy B and Moore, Elizabeth C and Cassiman, David and Van Damme-Lombaerts, Rita and Roskams, Tania},
  issn         = {0147-5185},
  journal      = {AMERICAN JOURNAL OF SURGICAL PATHOLOGY},
  keywords     = {bile duct paucity,Alagille syndrome,bile duct development,Jagged1 gene,liver transplantation,PRIMARY BILIARY-CIRRHOSIS,ARTERIOHEPATIC DYSPLASIA,JAG1 MUTATIONS,HUMAN JAGGED1,EXPRESSION,TRANSPLANTATION,CYTOKERATIN-7,MORPHOGENESIS,HYPERPLASIA,FREQUENCY},
  language     = {eng},
  number       = {6},
  pages        = {820--826},
  title        = {Peripheral bile duct paucity and cholestasis in the liver of a patient with Alagille syndrome: further evidence supporting a lack of postnatal bile duct branching and elongation},
  url          = {http://dx.doi.org/10.1097/01.pas.0000161325.36348.25},
  volume       = {29},
  year         = {2005},
}

Altmetric
View in Altmetric
Web of Science
Times cited: