Gene expression profiling to identify causes of graft injury in long term survivors of paediatric liver transplantation


Dr Nicola Ruth of Birmingham Women’s and Children’s Hospital NHS Foundation Trust discusses her research and what it means for the future of childhood liver disease treatment.


Deirdre Kelly, Professor of Hepatology, University of Birmingham & Birmingham Women’s & Children’s Hospital, Birmingham

Alberto Sanchez-Fueyo, Professor of Hepatology, King’s College Hospital, London

Stefan Hubscher, Leith Professor and Professor of Hepatic Pathology, University of Birmingham. Consultant Histopathologist, University Hospitals Birmingham NHS Foundation Trust

Carla Lloyd, Liver Unit, Birmingham Women’s and Children’s Hospital, Birmingham

What is the study looking at?

The long-term outcome of their liver transplant is evolving. The successful development of paediatric liver transplantation (LT) has greatly improved the prognosis of children with fatal liver disease who now live to become young adults. The focus has now moved to maintaining liver function in the transplanted liver. A number of centres have documented the consistent finding of inflammation (hepatitis) and development of scar tissue (fibrosis) in 75% of children despite normal blood tests. These findings are concerning for progressive liver disease and possibly the need for re-transplantation as the underlying causes remain unclear.

What this study hopes to achieve

  • This study will look at different genetic profiles (the make-up of DNA) in patients who have normal biopsies, those with rejection, hepatitis or fibrosis to identify risk factors which professionals may be able to prevent or treat. Investigators also hope that by examining genes in this way, with children of varying degrees of graft injury (inflammation or scarring), will enable the use of different immunosuppression regimes and therefore prevent progressive scarring and/or inflammation.

Why is this research important?

As survival after paediatric LT has improved and children grow into adult life, graft injury will play an increasingly important role and has implications for long-term survival. As the mechanisms of hepatitis and fibrosis remain unclear, it is essential to identify risk factors, which may be prevented or treated.

What about the future?

This study will add additional information to the pilot study previously carried out. From this project a multicentre study will be designed. If it is found that certain genes play a major role in how long the transplanted liver lasts, recipient and donor gene matching typing may be performed at transplant stage.