PKR gene expression and response to pegylated interferon plus ribavirin therapy in chronic hepatitis C

Martina Gerotto, Francesca Dal Pero, Gladis Bortoletto, Stefano Realdon, Alessia Ferrari, Silvia Boccato, Alfredo Alberti

Research output: Contribution to journalArticle

Abstract

Pegylated interferon (PEG-IFN) alpha combined with ribavirin is the current standard treatment for hepatitis C, but around 50% of patients do not respond for reasons that are not fully understood. To explore the regulation of IFN-inducible protein kinase (PKR), we have measured PKR mRNA levels in peripheral blood mononuclear cells (PBMCs) and in liver biopsies from patients with chronic hepatitis C. PBMCs were also analysed after in vitro incubation with IFN and during antiviral therapy. Non-responders to PEG-IFN plus ribavirin had pre-treatment PKR mRNA levels in PBMCs (0.1 ± 0.0074) and in liver (0.102 ± 0.051) that were significantly higher than those of responders (PBMCs: 0.023 ± 0.014, P=0.0005; liver: 0.034 ± 0.020; P=0.0002). On the other hand, PKR mRNA levels in PBMCs were similar in non-responders and in responders after in vitro exposure to IFN (0.434 ± 0.301 vs 0.403 ± 0.222; P=NS) and during therapy (0.31 ± 0.10 vs 0.30 ± 0.12; P=NS). These results indicate that in hepatitis C, non-responsiveness to IFN-alpha is associated with pre-treatment up-regulation of the PKR gene, evidence that the infecting hepatitis C virus is able to stimulate endogenous IFN production, being resistant to its antiviral effect. On the other hand, the PKR gene response to exogenous IFN was similar in responders and non-responders, at least in PBMCs, suggesting that variations in its activation are not major determinants of the outcome of antiviral treatment.

Original languageEnglish
Pages (from-to)763-770
Number of pages8
JournalAntiviral Therapy
Volume9
Issue number5
Publication statusPublished - Oct 2004

ASJC Scopus subject areas

  • Pharmacology

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    Gerotto, M., Dal Pero, F., Bortoletto, G., Realdon, S., Ferrari, A., Boccato, S., & Alberti, A. (2004). PKR gene expression and response to pegylated interferon plus ribavirin therapy in chronic hepatitis C. Antiviral Therapy, 9(5), 763-770.