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01.09.2011 | Original Article

Analysis of the complete open reading frame of hepatitis C virus in genotype 2a infection reveals critical sites influencing the response to peginterferon and ribavirin therapy

verfasst von: Makoto Kadokura, Shinya Maekawa, Ryota Sueki, Mika Miura, Kazuki Komase, Hiroko Shindo, Fumitake Amemiya, Tomoyoshi Uetake, Taisuke Inoue, Minoru Sakamoto, Mina Nakagawa, Naoya Sakamoto, Mamoru Watanabe, Nobuyuki Enomoto

Erschienen in: Hepatology International | Ausgabe 3/2011

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Abstract

Purpose

A proportion of patients infected with genotype 2a hepatitis C virus (HCV) cannot achieve a sustained virological response (SVR) to pegylated-interferon plus ribavirin therapy (PEG-IFN/RBV) but the reason remains unclear. The present study aimed to clarify the possible correlation between viral sequence variations and final outcome.

Methods

The pretreatment complete open reading frame (ORF) sequences of genotype 2a HCV were determined by direct sequencing for two independent groups of patients (43 patients as test; group 1 and 35 as validation; group 2), and the correlation with the final outcome was explored.

Results

Patients with SVR (n = 58) and with non-SVR (n = 20) differed significantly in pretreatment HCV RNA level (p = 0.002), fibrosis score (p = 0.047), and cumulative RBV dosage (p = 0.003). By comparison of all amino acid positions in the complete HCV ORFs, threonine at amino acid (aa) 110 in the core region was remarkably frequent in SVR (p = 0.01 for group 1, p = 0.004 for group 2, and p = 5E−05 for combined). A sliding window analysis revealed that the total number of amino acid variations within the NS5A aa 2258–2306 region were significantly high in SVR compared to non-SVR patients (p = 0.01 for group 1, p = 0.006 for group 2, and p = 0.0006 for combined). Multivariate analyses revealed that core aa 110 (p = 0.02), NS5A aa 2258–2306 (p = 0.03), and cumulative RBV dosage (p = 0.02) were identified as independent variables associated with the final outcome.

Conclusions

The outcome of PEG-IFN/RBV therapy is significantly influenced by variation in the core and NS5A regions in genotype 2a HCV infection.

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Titel: Analysis of the complete open reading frame of hepatitis C virus in genotype 2a infection reveals critical sites influencing the response to peginterferon and ribavirin therapy
verfasst von: Makoto Kadokura
Shinya Maekawa
Ryota Sueki
Mika Miura
Kazuki Komase
Hiroko Shindo
Fumitake Amemiya
Tomoyoshi Uetake
Taisuke Inoue
Minoru Sakamoto
Mina Nakagawa
Naoya Sakamoto
Mamoru Watanabe
Nobuyuki Enomoto
Publikationsdatum: 01.09.2011
Verlag: Springer-Verlag
Erschienen in: Hepatology International / Ausgabe 3/2011
Print ISSN: 1936-0533
Elektronische ISSN: 1936-0541
DOI: https://doi.org/10.1007/s12072-011-9267-x

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Analysis of the complete open reading frame of hepatitis C virus in genotype 2a infection reveals critical sites influencing the response to peginterferon and ribavirin therapy

Abstract

Purpose

Methods

Results

Conclusions

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Abstract

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