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Open Access Highly Accessed Research article

Core mutations, IL28B polymorphisms and response to peginterferon/ribavirin treatment in Swedish patients with hepatitis C virus genotype 1 infection

Erik Alestig1*, Birgitta Arnholm2, Anders Eilard1, Martin Lagging1, Staffan Nilsson3, Gunnar Norkrans1, Thomas Wahlberg4, Rune Wejstål1, Johan Westin1 and Magnus Lindh1

Author Affiliations

1 Department of Infection and Virology, University of Gothenburg, Gothenburg, Sweden

2 Infectious Diseases Clinic, Borås Hospital, Borås, Sweden

3 Chalmers University of Technology, Department of Mathematical Statistics, Gothenburg, Sweden

4 Infectious Diseases Clinic, Central Hospital, Skövde, Sweden

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BMC Infectious Diseases 2011, 11:124  doi:10.1186/1471-2334-11-124

Published: 12 May 2011

Abstract

Background

Patients infected with hepatitis C virus (HCV) genotype 1 respond poorly to standard treatment with 50% or less achieving sustained virologic response. Predicting outcome is essential and could help avoid unnecessary treatment and reduce health cost. Recently, an association of amino acid substitutions in the core region and treatment outcome was observed in Japanese patients. In the present study, the impact of these mutations on response kinetics and treatment outcome was explored in Caucasian patients.

Methods

The core region of HCV pre-treatment samples obtained from 50 patients treated with peginterferon/ribavirin in a previous Swedish clinical trial with genotype 1 infection were sequenced. The alleles at rs12979860, a single nucleotide polymorphism (SNP), were assessed in order to identify any co-association with this strong response predictor.

Results

No association between treatment response and substitutions of core residue 91 was found. In contrast, substitutions of core residue 70 were observed in 6/21 (29%) non-responders, but only in one of 29 responders (p = 0.03), and were more common in subgenotype 1b (R70Q in 6 of 13 strains) than in 1a (R70P in 1 of 37 strains, p = 0.004). The rs12979860 SNP upstream of the IL28B gene was overall the strongest response predictor (p = 0.0001). Core 70 substitutions were associated with poorer response kinetics in patients carrying the CT genotype at rs12979860.

Conclusions

The results indicate that substitutions of core residue 70 are related to treatment response in Caucasian patients with HCV-1b infection, but are of less importance than IL28B polymorphism.