The role of vascular adhesion protein-1 in the pathogenesis of chronic graft hepatitis and fibrosis after paediatric liver transplantation


Dr Steffen Hartleif of Graft Injury Group, Birmingham Children’s Hospital discusses his research and what it means for the future of treating childhood liver disease.

What is this study looking at?

Patient and graft survival after paediatric liver transplantation (pLT) has improved significantly. However, chronic graft hepatitis and fibrosis are common and account for long-term graft injury and graft loss after pLT. Currently, mechanisms of chronic graft hepatitis and fibrosis are incompletely understood and there is no specific treatment.

In other liver diseases associated with inflammation and fibrosis, the vascular adhesion protein-1 (VAP-1) plays an important role in immune responses that mediate liver injury. This study looks into whether VAP-1 also drives inflammation in chronic graft hepatitis.

Why is this research important?

As survival after paediatric LT has improved, chronic allograft hepatopathy is likely to play an increasingly important role for late morbidity and potentially also for long-term survival. However, the mechanisms of chronic allograft hepatitis and fibrosis after paediatric LT remain largely unclear. This study will contribute to assess a new pathway of alloimmune response after organ transplantation.

If we can confirm an important role for VAP-1 signalling pathways in graft hepatitis and fibrosis, soluble VAP-1 could serve as a novel biomarker. There is great medical need for biomarkers in order to monitor unapparent chronic graft hepatitis and to prevent severe graft fibrosis in children after LT.

What about the future?

If VAP-1 mediated pathways prove to be important in the development of late graft inflammation and fibrosis, there may be recommendations and interest in designing a multicentre study to investigate the possibility of implementing therapeutic strategies in children with progressive fibrosis after pLT.

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