Research Group

  • Prof. John Andrew Kirby, Principal Investigator
  • Prof. Alastair Burt, Co-Investigator
  • Dr Helen Robertson, Research Associate


  • University of Newcastle, Newcastle-upon-Tyne, UK


  • Examination of Bile Duct Changes after Liver Transplantation

A dense network of small ducts is present in the normal liver to allow free drainage of bile fluids into larger ducts and to the gut. The inner surface of these ducts is lined by a single layer of delicate biliary epithelial cells. Unfortunately, some inflammatory liver diseases, including chronic liver rejection and post-transplant recurrence of diseases such as primary biliary cirrhosis and primary sclerosing cholangitis, cause bile ducts to deteriorate and the epithelial cells to ‘disappear’; preventing normal bile drainage. We have already shown in the kidney that the epithelial cells which form tubules can be stimulated to transform directly into fibroblasts, which form scar tissue and we have shown that this transformation is an important process after kidney transplantation. Importantly, this damaging change can be caused by immune cells (white blood cells), which enter the transplanted liver from the recipient’s circulation and penetrate the bile duct walls, where they can adhere to the epithelial cells and interact with them, causing the epithelial cells to change their appearance and function. Clearly, any successful therapy for chronic liver rejection or recurrence of primary biliary cirrhosis and primary sclerosing cholangitis should be aimed at regenerating the bile ducts. For this reason, it is particularly exciting that recent data has shown that fibroblasts formed from kidney epithelial cells can be induced to change back into functional epithelial cells. We have designed this project to define the conditions which cause biliary epithelial cells to change into fibroblasts and, more importantly, to determine how this can be reversed in an animal model of chronic inflammatory liver disease. These results may suggest new treatments to prevent chronic changes within the transplanted liver, whatever the initial cause.

Progress Report
Final Report