Trinity Scientists Identify Risk Factors in the Development of Chronic Hepatitis C Virus Infection

Posted on: 07 April 2011

Risk factors in the development of chronic Hepatitis C Virus have been identified by Trinity scientists in research recently published in the Proceedings of the National Academy of Sciences.  The findings will help in determining the prognosis for individuals exposed to Hepatitis C Virus (HCV) and also have the potential of opening new avenues for the treatment of HCV infection.  The study was funded by the Irish Health Research Board and Science Foundation Ireland.

Hepatitis C virus is a common viral infection which can lead to chronic disease associated with liver cirrhosis and failure.  It is thought that the immune system plays an important role in patients that spontaneously clear the infection, however, as these patients may never know that they have been exposed to virus, identification of factors involved in viral clearance is extremely difficult. 

Trinity scientists have discovered two independent risk factors in the development of chronic infection that together synergise to increase the risk of chronic infection even further.  The researchers analysed the genes of over 540 Irish women that had been infected with HCV as a result of contaminated anti-D blood products.  They found that patients who developed chronic HCV infection were more likely to possess particular variants of two genetic sequences: the first was the gene for KIR2DS3, a receptor expressed by Natural Killer cells, cells of the immune system that kill virally infected and cancer cells.  The second risk factor was a single genetic mutation (SNP) near a gene called interleukin-28B.  This gene encodes a cytokine, a soluble mediator produced by the immune system which has anti-viral activities.  The research was carried out in the laboratory of Dr Clair Gardiner in Trinity’s School of Biochemistry and Immunology.

Commenting on the significance of the findings, Dr Clair Gardiner said: “The findings are exciting as they support the importance of the early immune response in determining disease progression in HCV infection.  We are the first to discover a link between Natural Killer cells and Interleukin-28B. Understanding how these cells and molecules interact will not only help us understand how HCV infection progresses but may also provide novel targets for therapy in HCV infected individuals.”

Patients who took part in the study were attending St James’s Hospital; St Vincent’s University Hospital; Mater Misericordiae Hospital in Dublin and University Hospital, Cork. 

Co-authors on the study are: Megan Dring, PhD; Maria Morrison; Brian McSharry PhD; Kieran Guinan, PhD; Richard Hagan PhD, IBTS, Dublin 8; Cliona O’Farrelly, PhD and the Irish Hepatitis C Research Consortium. 

Irish HCV Consortium members: Gary Courtney, Orla Crosbie, John Crowe, John Hegarty, Dermot Kelleher, Emer Lawlor, John Lee, Susan McKiernan, Frank Murray, Suzanne Norris, Cliona O’Farrelly and Leila Thornton.