- Dr Nazia Selzner, Principal Investigator
- Dr Ian D. McGilvray, Co-Investigator
- Dr Eberhard Renner, Co-Investigator
- Dr Guindi Maha, Co-Investigator
- Dr Ayedi Oyedel, Co-Investigator
- Toronto General Hospital, Toronto, Canada
- Improving Outcomes of Hepatitis C-infected Patients after Liver Transplantation
Hepatitis C virus (HCV) infection is a common indication for liver transplantation. All grafts are re-infected with hepatitis C virus after transplantation, often resulting in the development of new disease in the liver graft, in many cases with redevelopment of cirrhosis (scaring of the liver). One important contributor to aggressive virus re-infection is likely the hepatic preservation/ischemia-reperfusion injury (P-IRI), which happens during organ preservation in the cold solution and at the reperfusion of the new graft during liver transplantation. This relation may be due to the effect of P-IRI on the interferon (IFN) response, which is an important mechanism of host defence against viral infection. Different hosts have different IFN responses to viral infection, and thus have different clinical outcomes. Our group was the first to describe how chronic HCV infection leads to two discrete types (phenotypes) of response to antiviral therapy with distinct expression of a subset of genes. How and whether these IFN-response phenotypes determine outcomes of HCV after liver transplantation is unknown.
The purpose of this study is to explore the role of P-IRI on the expression of genes that are important in the host antiviral defence and to correlate it with clinical outcomes of HCV recipients.
Our hypothesis is that P-IRI occurring during liver transplantation results in changes of antiviral defence mediators of the host and thus contributes to an aggressive re-infection of the graft post liver transplantation.
Our aim is to:
1. Confirm the role of P-IRI in HCV re-infection of the graft post-liver transplantation;
2. Identify which genes and markers are affected by P-IRI during the course of liver transplantation for HCV;
3. Identify if these markers are associated with the worse outcomes after liver transplantation.