- Prof. Jane McKeating, Principal Investigator
- Dr Ian Rowe, Co-Investigator
- Prof. Stefan Hubscher, Co-Investigator
- Prof. David Adams, Co-Investigator
- Dr David Mutimer, Co-Investigator
- Dr Peter Balfe, Collaborator
- Prof. Alan Perelson, Collaborator
- Prof. Flossie Wong-Staal, Collaborator
- Prof. Jeffrey McKelvy, Collaborator
- University of Birmingham, Birmingham, UK
- Do HCV-Receptor Interactions Determine the Outcome of Liver Transplant?
Hepatitis C virus (HCV)-associated liver disease is one of the main reasons for liver transplantation in adults. Unfortunately, HCV infects the newly transplanted liver in all cases. After liver transplantation some patients recover well and have an extended period of relatively good health with few symptoms of HCV disease. In contrast, approximately one third of patients show a rapid decline in the function of their transplanted organ, with signs of HCV-associated fibrosis and liver impairment within the first year. Many of these patients go on to develop cirrhosis and require re-transplantation within 5 years. Given the shortage of donor organs and the increasing number of patients requiring re-transplant due to HCV-induced cirrhosis, identifying ways to improve allograft survival in HCV-infected patients is an important research focus.
Like all other viruses, HCV initiates infection by attaching to molecules or receptors on the cell surface. Recent advances have identified the cellular molecules defining HCV infection of liver cells. We have recently shown that HCV strains can differ in their interaction with host cell receptors and this will have significant consequences for the infectivity and growth of the virus in the liver. We hypothesize that differences in HCV-receptor interactions will influence how the virus repopulates the newly transplanted liver. We plan to use molecular and biological methods to discriminate between transmitting strains that lead to progressive disease and those that do not. These studies will help us understand the molecular events that control HCV transmission and will allow us to direct future treatment.