ANNUAL REVIEW master Final3a - St Vincent's University Hospital

St. Vincent’s Healthcare Group Limited - Annual Review 2007
Education & Research
We have also been awarded a grant from the HRB of €299,379 for “Suppressor Of Cytokine Signalling
(SOCS) Protein Involvement In ChronicHepatitis C Virus (HCV) Infection and Failure to Respond to Interferon
Alpha Therapy”. We have observed that PBMC’s from patients with sustained virologic response (SVR)
produced higher levels of growth factors than non-responding patients after IFN-alpha/ribavirin treatment.
These findings indicate that an intracellular blockade of IFN-alpha signalling occurs in PBMC’s from some
HCV infected patients. We propose to define the molecular basis for this blockade.
SOCS proteins control cytokine signalling and have been documented to regulate IFN-alpha signal
transduction and be triggered by HCV infection. Therefore, plan to focus on SOCS proteins and their effects
on ISG and growth factor expression levels. Using siRNA technology, we aim to identify the downstream
molecular targets of SOCS interference. This will be the first study of its kind to compare the cellular
response to IFN-alpha/ribavirin treatment using primary human haematopoietic cells in healthy, recovered
and chronic HCV patients. We also aim to determine whether the failure to respond to IFN-alpha treatment
is mediated primarily in hepatocytes or immune cells. A primary outcome of this study will be a novel
signature of response to treatment, based on SOCS, ISG and growth factor expression by PBMC’s.
Identification of non-responding patients prior to treatment will avoid unnecessary side effects
Oral Presentations
M. B. Zaman. Activation of the transcription factor NRF-2 in donor liver during ischemia reperfusion is
associated with less inflammatory damage and lower trasaminase levels post-transplant. International Liver
Transplant Society (ILTS) June 20-23 2007 – Brazil
C. O’ Farrelly. The Liver: A Sentinel of Danger. International Liver Transplant Society (ILTS) June 20-23 2007
– Brazil
E. Ryan, J. Hegarty, C. O’Farrelly. GMCSF may modulate the response to IFN-alpha in Chronic Hepatitis C
Virus (HCV) infection. Keystone Viral Immunity Conference Jan 20-25 2008 – Colorado.
A. G. Rowan, E. J. Ryan, J. E. Hegarty, C. O’ Farrelly, K. H. G. Mills. IL-10 and TGF-β mediated suppression of
antigen-specific Th1 and Th17 responses during hepatitis C virus infection. British Society of Immunology.
Feb 20-23 2007 Glasgow
Poster Presentations
T. Tajuddin, E. Ryan, C. Keogh, S. Norris, C. O’ Farrelly, J. Hegarty. Suppressed Granulocyte Colony Stimulating
Factor Production in Chronic Hepatitis C Patients on Interferon –Alpha (IFN-α) Therapy; Possible Role in
IFN-· Induced Neutropenia. Irish Society of Gastroenterology Nov 29-30 2007 – Clontarf Castle, Dublin
T. Tajuddin, E. Ryan, L. Gallagher, E. McGrath, J. Hegarty & C. O’ Farrelly. Expression of G-CSF in Chronic
Hepatitis C Virus (HCV) infection; implications for the outcome of IFN-α/Ribavirin therapy. Irish Society of
Gastroenterology April 19-20 2007 – Killarney, Kerry
T. Tajuddin, E. Ryan, J. Hegarty & C. O’ Farrelly. GM-CSF may modulate the response to therapeutic IFN-· in
Chronic Hepatitis C Virus (HCV) infection. American Association for the Study of Liver Diseases (AASLD)
Nov 2-6 2007 - Boston
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