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Liver Gene Expression Signature to Predict Response to Pegylated interferon plus Ribavirin combination therapy in Patients with Chronic Hepatitis C
  1. Tarik Asselah (tarik.asselah{at}bjn.aphp.fr)
  1. Pôle des Maladies de l'Appareil Digestif and INSERM U773, CRB3, University of Paris VII, France
    1. Ivan Bieche
    1. INSERM U 745 and University Paris V, France
      1. Stéphanie Narguet
      1. INSERM U 745 and University Paris V, France
        1. Audrey Sabbagh
        1. INSERM U 745 and University Paris V, France
          1. Ingrid Laurendeau
          1. INSERM U 745 and University Paris V, France
            1. Marie-Pierre Ripault
            1. Pôle des Maladies de l'Appareil Digestif and INSERM U773, CRB3, University of Paris VII, France
              1. Nathalie Boyer
              1. Pôle des Maladies de l'Appareil Digestif and INSERM U773, CRB3, University of Paris VII, France
                1. Michéle Martinot-Peignoux
                1. Pôle des Maladies de l'Appareil Digestif and INSERM U773, CRB3, University of Paris VII, France
                  1. Dominique Valla
                  1. Pôle des Maladies de l'Appareil Digestif and INSERM U773, CRB3, University of Paris VII, France
                    1. Michel Vidaud
                    1. INSERM U 745 and University Paris V, Service de Biochimie, Hôpital Beaujon, France
                      1. Patrick Marcellin
                      1. Pôle des Maladies de l'Appareil Digestif and INSERM U773, CRB3, University of Paris VII, France

                        Abstract

                        Background and Aims The gold standard treatment of chronic hepatitis C is the combination of pegylated interferon plus ribavirin. Considering side effects and treatment cost, prediction of treatment response before therapy is important. The aim of our study was to identify a liver gene signature to predict sustained virological response in patients with chronic hepatitis C.

                        Patients and Methods Group A (training set): 40 patients with chronic hepatitis C including 14 non responders and 26 sustained responders. Group B (validation set): 29 patients including 9 non responders and 20 sustained responders. Eleven responder-relapsers were also included. We selected 58 genes from the literature, associated with liver gene expression dysregulation during chronic hepatitis C. Real-time quantitative RT-PCR assays was used to analyse the mRNA expression of these 58 selected genes in liver biopsy specimens taken from the patients before treatment.

                        Results From the Group A data, we identified three genes whose expression was significantly increased in non responders compared to sustained responders: IFI-6-16/G1P3, IFI27 and ISG15/G1P2. These three genes also showed significant differences in their expression profiles between non responders and responders in the independent sample (Group B). Supervised class prediction analysis identified a two-gene (IFI27 and CXCL9) signature, which accurately predicted treatment response in 79.3% (23/29) of patients from the validation set (Group B), with a predictive accuracy of 100% (9/9) and of 70% (14/20) in non responders and sustained responders, respectively. Expression profiles of responder-relapsers did not differ significantly from those of non responders and responders and 73% (8/11) of them were predicted as responders with the two-gene classifier.

                        Conclusion Non responders and responders have different liver gene expression profiles before treatment. The most notable changes mainly occurred in the interferon stimulated genes. Treatment response could be predicted with a two-gene signature (IFI27 and CXCL9).

                        • interferon pathway
                        • microarray
                        • molecular signature
                        • signalling pathways
                        • treatment response

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