ANNUAL REVIEW master Final3a - St Vincent's University Hospital

St. Vincent’s Healthcare Group Limited - Annual Review 2007
Education & Research
HCV Research Consortium
The cohort of Irish women infected in 1977 with HCV contaminated anti-D provide an important opportunity
for analysis of host genetic factors in HCV as this group is homogenous for time of infection, route of
infection, racial background, gender and viral subtype. Resolution rates in this cohort have been significantly
better than the average reported rates of approximately 20% and several preliminary studies of these
patients have suggested genetic influences including association between HLA and viral clearance and also
an association between MMP3 and chronicity. The Consortium will investigate the contribution of KIR
genotype and/or phenotype to resolution of HCV in the Irish population.
The HCV Research Consortium was established to conduct research into different aspects of HCV infection
in this cohort. Profs O’ Farrelly and Hegarty coordinate the HCV Research Consortium; which includes Irish
clinicians who have a research interest in HCV infection.
Prof. Cliona O'Farrelly, Chairperson, Trinity College Dublin
Prof. John Hegarty, St. Vincent's University Hospital
Dr. John Crowe, Mater Misericordeae Hospital
Dr. Orla Crosbie, Cork University Hospital
Dr. Frank Murray, Beaumont Hospital
Dr. Suzanne Norris, St. Jame’s Hospital
Prof. Dermot Kelleher, St. James Hospital
Dr. Aideen Long, St. James Hospital
Dr. Lelia Thornton, National Disease Surveillance Centre
Grants
The group has been awarded a Translational Programme grant from the HRB of €1,302,467.40 for ‘Immune
targeting strategies: improving the response rate to IFN-alpha/ribavirin therapy in chronic Hepatitis C Virus
infection.’ With the help of HCV patients being cared for by the Irish HCV Research Consortium, a primary
aim of this study is to develop a test for predicting responsive and non-responsive patients. We have
preliminary evidence that the IFN-alpha activated JAK/STAT signalling pathway is compromised in nonresponsive
patients and this defect can be detected in vitro prior to treatment. Using samples from our cohort
of anti-D infected women, we propose to identify an IFN-alpha response gene signature predictive of
treatment
outcome.
We have demonstrated that the envelope protein from HCV, E2, can inhibit the protein kinase C (PKC)
signalling pathway. Inhibition of classical PKC has previously been associated with attenuation of IFN-alpha
signalling. Thus, we will investigate the role of PKC in the molecular mechanisms of IFN-alpha resistance in
HCV and the impact of G-CSF on these pathways. We thus aim to provide a rationale for its inclusion in the
treatment regimen of the sub group of patients which demonstrate HCV induced inhibition of JAK/STAT
signalling.
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