Core mutations, IL28B polymorphisms and response to peginterferon/ribavirin treatment in Swedish patients with hepatitis C virus genotype 1 infection
Artikel i vetenskaplig tidskrift, 2011

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.

sustained

pegylated interferon

plus ribavirin

predictors

ribavirin combination therapy

ns5a region

virological response

amino-acid substitutions

dynamics

genetic-variation

clearance

Författare

Erik Alestig

Göteborgs universitet

B Arnholm

Boras Hospital

Anders Eilard

Göteborgs universitet

Martin Lagging

Göteborgs universitet

Staffan Nilsson

Göteborgs universitet

Chalmers, Matematiska vetenskaper, matematisk statistik

Gunnar Norkrans

Göteborgs universitet

T Wahlberg

Central Hospital Skovde

Rune Wejstål

Göteborgs universitet

Johan Westin

Göteborgs universitet

Magnus Lindh

Göteborgs universitet

BMC Infectious Diseases

1471-2334 (ISSN)

Vol. 11 124

Ämneskategorier

Klinisk medicin

Mikrobiologi inom det medicinska området

DOI

10.1186/1471-2334-11-124