Interferon-stimulated gene expression in chronic hepatitis C virus genotype 1 infected patients treated with the NS3/4A protease inhibitor faldaprevir in combination with pegylated interferon alpha-2a/ribavirin
Keywords: HCV, ISGs IFNA4, DDX58, IRF3, IFI27, RSAD2
The objective of this study was to investigate the expression of selected interferon-stimulated genes (ISGs) in PBMC (peripheral blood mononuclear cell) prior and during the treatment with NS3/NS4A protease inhibitor faldaprevir plus pegylated interferon alpha-2a/ribavirin (PegIFN/RBV) in treatment-naïve and treatment-experienced chronic hepatitis C virus genotype 1 infected patients. This thesis was performed in three consecutive steps. First, we selected 95 most representative ISGs based on the literature. Secondly, we selected 30 patients for the SVR-oriented exploratory screening and tested all 95 genes in these patients. Finally, we tested 15 genes identified during the SVR-oriented exploratory screening in all patients eligible for this study (N = 263). As a result, we identified 15 genes which may play a role in the treatment response to faldaprevir plus PegIFN/RBV. Five ISGs (IFNA4, DDX58, IRF3, IFI27 and RSAD2) showed association with SVR at various time points. Baseline expression of two ISGs (IFNA4 and DDX58) was strongly associated with SVR. In conclusion, our data showed that the baseline expression of two genes (IFNA4 and DDX58) might be predictive of SVR in the treatment-naïve and treatment-experienced HCV GT1a and 1b infected patients treated with NS3/NS4A protease inhibitor faldaprevir plus PegIFN/RBV. Treatment-naïve patients had lower baseline expression of ISGs and more pronounced gene induction during the treatment as compared to the treatment-experienced patients. SVR patients had lower baseline expression and higher induction of ISGs during the treatment. IFNA4 and DDX58 should be considered for further investigations in prospective studies to confirm their predictive role for the treatment success of interferon-containing treatment regimens combined with protease inhibitors.