Biliary - posttransplantation recurrence of PBC

[Guest guest]

Hepatology. 2007

Biliary epithelial-mesenchymal transition in posttransplantation

recurrence of primary biliary cirrhosis.

on H, Kirby JA, Yip WW, DE, Burt AD.

Applied Immunobiology &

Transplantation Research Group, Newcastle University, Newcastle-upon-Tyne, UK.

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-beta) 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-beta. 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.

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