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dc.contributor.authorSTEVENSON, NIGELen
dc.contributor.authorO'FARRELLY, CLIONAen
dc.contributor.authorBOURKE, NOLLAIGen
dc.date.accessioned2014-08-06T15:17:59Z
dc.date.available2014-08-06T15:17:59Z
dc.date.issued2014en
dc.date.submitted2014en
dc.identifier.citationBourke NM, O'Neill M, Sarwar S, Norris S, Stewart S, Hegarty JE, Stevenson NJ and O'Farrelly C., In vitro Blood Cell Responsiveness to IFN-alpha Predicts Clinical Response Independently of IL28B in Hepatitis C Virus Genotype 1 Infected Patients., Journal of Translational Medicine, 2014, 204-en
dc.identifier.otherYen
dc.descriptionPUBLISHEDen
dc.description.abstractBACKGROUND: Treatment with interferon-alpha (IFN-α) and ribavirin successfully clears hepatitis C virus (HCV) infection in 50% of patients infected with genotype 1. Addition of NS3-4A protease inhibitors (PIs) increases response rates but results in additional side effects and significant economic costs. Here, we hypothesised that in vitro responsiveness of peripheral blood mononuclear cells (PBMCs) to IFN-α stimulation would identify patients who achieved sustained virological response (SVR) on dual therapy alone and thus not require addition of PIs. METHODS: PBMCs were isolated from HCV infected patients (n = 42), infected with either HCV genotype 1 or genotype 3, before commencing therapy and stimulated in vitro with IFN-α. Expression of the IFN stimulated genes (ISGs) PKR, OAS and MxA was measured and correlated with subsequent treatment response and IL28B genotype. RESULTS: Genotype 1 infected patients who achieved SVR had significantly higher pre-treatment expression of PKR (p = 0.0148), OAS (p = 0.0019) and MxA (p = 0.0019) in IFN-α stimulated PBMCs, compared to genotype 1 infected patients who did not achieve SVR or patients infected with genotype 3, whose in vitro ISG expression did not correlate with clinical responsiveness. IL28B genotype (rs12979860) did not correlate with endogenous or IFN-α stimulated ISG responsiveness. CONCLUSIONS: In vitro responsiveness of PBMCs to IFN-α from genotype 1 infected patients predicts clinical responsiveness to dual therapy, independently of IL28B genotype. These results indicate that this sub-group of HCV infected patients could be identified pre-treatment and successfully treated without PIs, thus reducing adverse side effects and emergence of PI resistant virus while making significant economic savings.en
dc.format.extent204en
dc.language.isoenen
dc.relation.ispartofseriesJournal of Translational Medicineen
dc.rightsYen
dc.subjectIL28B genotypeen
dc.subjectHost predictive markersen
dc.subjectProtease inhibitorsen
dc.subjectInterferon stimulated genes;en
dc.titleIn vitro Blood Cell Responsiveness to IFN-alpha Predicts Clinical Response Independently of IL28B in Hepatitis C Virus Genotype 1 Infected Patients.en
dc.typeJournal Articleen
dc.type.supercollectionscholarly_publicationsen
dc.type.supercollectionrefereed_publicationsen
dc.identifier.peoplefinderurlhttp://people.tcd.ie/stevennjen
dc.identifier.peoplefinderurlhttp://people.tcd.ie/nbourkeen
dc.identifier.peoplefinderurlhttp://people.tcd.ie/ofarreclen
dc.identifier.rssinternalid94751en
dc.identifier.doihttp://dx.doi.org/10.1186/1479-5876-12-206en
dc.rights.ecaccessrightsopenAccess
dc.subject.TCDThemeGenes & Societyen
dc.subject.TCDThemeImmunology, Inflammation & Infectionen
dc.subject.TCDTagANTIVIRAL ACTIVITYen
dc.subject.TCDTagHEPATITIS C VIRUSen
dc.subject.TCDTagImmune systemen
dc.subject.TCDTagImmunology, Immunotherapyen
dc.subject.TCDTagMolecular Biologyen
dc.subject.TCDTagSIGNAL-TRANSDUCTION PATHWAYSen
dc.identifier.orcid_id0000-0002-6966-9314en
dc.contributor.sponsorHealth Research Board (HRB)en
dc.contributor.sponsorGrantNumberTRA/2007/14en
dc.contributor.sponsorScience Foundation Ireland (SFI)en
dc.contributor.sponsorGrantNumber08/RFP/BMT1403en
dc.identifier.urihttp://hdl.handle.net/2262/70712


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