Suppressor of cytokine signaling 1 expression in peripheral blood mononuclear cells of hepatitis C genotype 1 patients.

Abstract

While new direct-acting antiviral therapies for hepatitis C virus (HCV) are the standard of care, interferon-α (IFN-α) remains a standard therapy in Taiwan based on its low cost and high response rate to IFN-α-based therapy. IFN-α exerts antiviral activity by inducing the expression of hundreds of genes that establish an antiviral state via Jak kinase (JAK)/signal transducers and activators of transcription (STAT) signaling. We quantified the transcript levels of JAK/STAT signaling genes in peripheral blood mononuclear cells of HCV genotype 1 patients and estimated the correlation between transcript levels and patient responses to IFN-α-based therapy. A total of 100 HCV genotype 1 naïve patients were enrolled. All patients received response-guided therapy for 24-48weeks with pegylated IFN-α and ribavirin. Peripheral blood mononuclear cells were collected before treatment. Twenty patients with sustained virological responses (SVR) and 20 patients without SVR were selected for a JAK/STAT signaling genes transcript analysis using multiplex reverse transcription-polymerase chain reaction. Transcripts that were upregulated or downregulated were further validated in 100 patients. Suppressor of cytokine signaling 1 (SOCS1) expression was upregulated in SVR patients compared with non-SVR patients (relative quantification=2.14) based on a multiplex reverse transcription-polymerase chain reaction analysis. We further analyzed SOCS1 expression in 100 patients. We found that SOCS1 expression did not differ significantly between SVR and non-SVR patients. Peripheral blood SOCS1 expression before treatment was not associated with SVR in HCV genotype 1 patients treated with pegylated IFN-α and ribavirin.