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Biliary epithelial-mesenchymal transition in posttransplantation recurrence of primary biliary cirrhosis

Lookup NU author(s): Dr Helen Robertson, Professor John Kirby, Professor David Jones, Professor Alastair Burt

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Abstract

Primary biliary cirrhosis (PBC) recurs in the allograft after liver transplantation. Study of early tissue changes in the time-course of disease recurrence provides a unique insight into the initial stages of the disease process, which, in nontransplant patients, occurs long before clinical presentation. We describe a patient who developed classical clinical, biochemical, immunological, and histological features of PBC within 9 months after transplantation. Use of tissue from this patient before and during the development of PBC allowed us to identify biliary epithelial cell (BEC) epithelial-mesenchymal transition (EMT) as a key pathogenetic process. BEC expression of S100A4 (an early fibroblast lineage marker established as a robust marker of EMT), vimentin, and pSmad 2/3 [a marker of transforming growth factor beta (TGF-β) pathway signaling] were identified immunohistochemically in most BECs in liver tissue from this patient at the point of diagnosis of recurrent disease. BEC expression of S100A4 and pSmad 2/3 was seen as early as 24 days after orthotopic liver transplantation (OLT), although no other features of recurrent PBC were present at this time. Conclusion: S100A4, vimentin, and pSmad 2/3 expression in early recurrent PBC after OLT suggests that BEC EMT is occurring (potentially explaining BEC loss) and that this process is driven by TGF-β. S100A4 expression by BEC appears to occur before the development of any other features of recurrent PBC, suggesting that EMT may be an initiating event. Copyright © 2007 by the American Association for the Study of Liver Diseases.


Publication metadata

Author(s): Robertson H, Kirby JA, Yip WW, Jones DEJ, Burt AD

Publication type: Article

Publication status: Published

Journal: Hepatology

Year: 2007

Volume: 45

Issue: 4

Pages: 977-981

Print publication date: 01/04/2007

ISSN (print): 0270-9139

ISSN (electronic): 1527-3350

Publisher: Wiley-Blackwell

URL: http://dx.doi.org/10.1002/hep.21624

DOI: 10.1002/hep.21624

PubMed id: 17393507


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