In vitro blood cell responsiveness to IFN-a predicts clinical response independently of IL28B in hepatitis C virus genotype 1 infected patients

Hdl Handle:
http://hdl.handle.net/10147/324257
Title:
In vitro blood cell responsiveness to IFN-a predicts clinical response independently of IL28B in hepatitis C virus genotype 1 infected patients
Authors:
Bourke, Nollaig M; O’Neill, Mary-Teresa; Sarwar, Shahzad; Norris, Suzanne; Stewart, Stephen; Hegarty, John E; Stevenson, Nigel J; O’Farrelly, Cliona
Citation:
Bourke NM et al. In vitro blood cell responsiveness to IFN predicts clinical response independently of IL28B in hepatitis C virus genotype 1 infected patients. J Transl Med. 2014 Jul 21;12(1):206
Issue Date:
21-Jul-2014
URI:
http://dx.doi.org/10.1186/1479-5876-12-206; http://hdl.handle.net/10147/324257
Abstract:
Abstract Background 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.
Item Type:
Article
Language:
en
Keywords:
HEPATITIS C

Full metadata record

DC FieldValue Language
dc.contributor.authorBourke, Nollaig Men_GB
dc.contributor.authorO’Neill, Mary-Teresaen_GB
dc.contributor.authorSarwar, Shahzaden_GB
dc.contributor.authorNorris, Suzanneen_GB
dc.contributor.authorStewart, Stephenen_GB
dc.contributor.authorHegarty, John Een_GB
dc.contributor.authorStevenson, Nigel Jen_GB
dc.contributor.authorO’Farrelly, Clionaen_GB
dc.date.accessioned2014-08-05T14:05:33Z-
dc.date.available2014-08-05T14:05:33Z-
dc.date.issued2014-07-21-
dc.identifier.citationBourke NM et al. In vitro blood cell responsiveness to IFN predicts clinical response independently of IL28B in hepatitis C virus genotype 1 infected patients. J Transl Med. 2014 Jul 21;12(1):206en_GB
dc.identifier.urihttp://dx.doi.org/10.1186/1479-5876-12-206-
dc.identifier.urihttp://hdl.handle.net/10147/324257-
dc.description.abstractAbstract Background 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.-
dc.language.isoenen
dc.subjectHEPATITIS Cen_GB
dc.titleIn vitro blood cell responsiveness to IFN-a predicts clinical response independently of IL28B in hepatitis C virus genotype 1 infected patientsen_GB
dc.typeArticleen
dc.language.rfc3066en-
dc.rights.holderNollaig M Bourke et al.; licensee BioMed Central Ltd.-
dc.description.statusPeer Reviewed-
dc.date.updated2014-07-28T15:13:49Z-
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