Early gene expression profiles of patients with chronic hepatitis C treated with pegylated interferon-alfa and ribavirin

Abstract

Responsiveness to hepatitis C virus (HCV) therapy depends on viral and host factors. Our aim was to assess sustained virologic response (SVR)-associated early gene expression in patients with HCV receiving pegylated interferon-alpha2a (PEG-IFN-␣2a) or PEG-IFN␣2b and ribavirin with the duration based on genotypes. Blood samples were collected into PAXgene tubes prior to treatment as well as 1, 7, 28, and 56 days after treatment. From the peripheral blood cells, total RNA was extracted, quantified, and used for one-step reverse transcription polymerase chain reaction to profile 154 messenger RNAs. Expression levels of messenger RNAs were normalized with six "housekeeping" genes and a reference RNA. Multiple regression and stepwise selection were performed to assess differences in gene expression at different time points, and predictive performance was evaluated for each model. A total of 68 patients were enrolled in the study and treated with combination therapy. The results of gene expression showed that SVR could be predicted by the gene expression of signal transducer and activator of transcription-6 (STAT-6) and suppressor of cytokine signaling-1 in the pretreatment samples. After 24 hours, SVR was predicted by the expression of interferon-dependent genes, and this dependence continued to be prominent throughout the treatment. Conclusion: Early gene expression during anti-HCV therapy may elucidate important molecular pathways that may be influencing the probability of achieving virologic response. (HEPATOLOGY 2009;49:763-774.)

Human Interferon Regulatory Factor 2 Gene Expression is Induced in Chronic Hepatitis C Virus Infection—A Possible Mode of Viral Persistence

“…This might have some implications regarding the role of pretherapeutic lower level of IRF-2 in predicting sustained virological response (SVR) in previously treated CHC subjects. 26 Our data are in contrast to the finding that IFN-α gene expression is downregulated in the liver but upregulated in PBMC of CHC subjects. 13 However, our data are in accordance with a recent report where IRF-2 expression was shown to be upregulated with enhanced IRF-2 oncogenic protein expression in CD19-positive blood B cells obtained from CHC subjects.…”

The Treatment Response of Chronically Hepatitis C Virus-Infected Patients Depends on Interferon Concentration but Not on Interferon Gene Expression in Peripheral Blood Mononuclear Cells

“…Other groups described that gene expression in PBMCs was predictive of treatment outcome (10,36). One group demonstrated that the expression of STAT6 and SOCS1 was predictive of the SVR in pretreatment samples (36).…”

“…One group demonstrated that the expression of STAT6 and SOCS1 was predictive of the SVR in pretreatment samples (36). These genes were not included in our assay.…”

Association of Serum Adipocytokines with Hepatic Steatosis and Fibrosis in Patients with Chronic Hepatitis C

“…Our findings indicate that the development of non-invasive diagnostic biomarkers reliably differentiating chronic hepatitis C patients with and without steatosis will require an expanded list of the variables, or will have to resort to imaging technologies [33]. A potential source for additional candidate biomarkers would be gene expression or proteomic endpoints [34,35]. On the other hand, the insights derived from attempts to build these models further support the genotype-specific pathogenesis of hepatic steatosis in chronic hepatitis C infection.…”