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Significance of variants associated with resistance to NS5A inhibitors in Japanese patients with genotype 1b hepatitis C virus infection as evaluated using cycling-probe real-time PCR combined with direct sequencing

  • Original Article—Liver, Pancreas, and Biliary Tract
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Abstract

Background

Dual oral therapy with daclatasvir plus asunaprevir yielded an SVR rate of 85 % among patients with genotype 1b HCV. Treatment failure mainly occurred in patients with pre-existing HCV with NS5A-Y93H mutation. The significance of the mutation was evaluated.

Methods

The percent of serum NS5A-Y93H strains relative to the total strains was quantified using cycling-probe real-time PCR combined with direct sequencing in 444 patients with genotype 1b HCV, and the factors associated with mutation were analyzed. The mutation rates during interferon therapy were measured sequentially.

Results

NS5A-Y93H strains (1–100 % of the total strains) were detected in 87 patients (19.6 %). Mutant strains were detected more frequently among women than among men, in patients with a favorable allele in the IL28B-related gene SNP than among those with unfavorable alleles, and among patients without HCC and/or with serum AFP levels less than 6.0 ng/ml than among those with HCC and/or levels of 6.0 ng/ml or more. A multivariate analysis revealed that IL28B-related gene polymorphisms were significant factors associated with mutant strains. Although the frequency of patients with mutant strains was equivalent among patients depending on their previous interferon therapies, a sequential analysis during the interferon administrations revealed that the mutant strains disappeared earlier than the wild-type strains.

Conclusions

NS5A-Y93H mutation was associated with sex, serum AFP levels, and IL28B-related gene polymorphisms in patients infected with genotype 1b HCV. The indications for NS5A inhibitor use should be determined based on these factors, since mutant strains seem to be sensitive to interferon.

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Authors and Affiliations

  1. Department of Gastroenterology and Hepatology, Faculty of Medicine, Saitama Medical University, 38 Morohongo, Moroyama-Machi, Iruma-Gun, Saitama, 350-0495, Japan

    Yoshihito Uchida, Jun-ichi Kouyama, Kayoko Naiki, Kayoko Sugawara, Satsuki Ando, Masamitsu Nakao, Daisuke Motoya, Mie Inao, Yukinori Imai, Nobuaki Nakayama & Satoshi Mochida

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  1. Yoshihito Uchida
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  2. Jun-ichi Kouyama
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  3. Kayoko Naiki
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  4. Kayoko Sugawara
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  5. Satsuki Ando
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  6. Masamitsu Nakao
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  7. Daisuke Motoya
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Correspondence to Satoshi Mochida.

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Conflict of interest

Satoshi MOCHIDA has received research grants, speaking fees or honoraria from Bristol Myers Squibb, Chugai Pharmaceutical, Dainippon, Mitsubishi Tanabe Pharma Corporation, MSD K.K., Toray Medical Co. Ltd., Ajinomoto Pharmaceuticals Co. Ltd., Eisai Co. Ltd. Satoshi MOCHIDA, Yoshihito UCHIDA, Jun-ichi KOUYAMA and Kayoko NAIKI has received patent royalties from SRL Inc.

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Uchida, Y., Kouyama, Ji., Naiki, K. et al. Significance of variants associated with resistance to NS5A inhibitors in Japanese patients with genotype 1b hepatitis C virus infection as evaluated using cycling-probe real-time PCR combined with direct sequencing. J Gastroenterol 51, 260–270 (2016). https://doi.org/10.1007/s00535-015-1106-8

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  • DOI: https://doi.org/10.1007/s00535-015-1106-8

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