Mixed HCV infection of genotype 1b and other genotypes influences non-response during daclatasvir + asunaprevir combination Therapy

Nozomu Wada, Fusao Ikeda, Chizuru Mori, Koichi Takaguchi, Shin Ichi Fujioka, Haruhiko Kobashi, Yoichi Morimoto, Kazuya Kariyama, Kosaku Sakaguchi, Noriaki Hashimoto, Akio Moriya, Mitsuhiko Kawaguchi, Hirokazu Miyatake, Hiroaki Hagihara, Junichi Kubota, Hiroki Takayama, Yasuto Takeuchi, Tetsuya Yasunaka, Akinobu Takaki, Yoshiaki IwasakiHiroyuki Okada

Research output: Contribution to journalArticle

Abstract

Daclatasvir (DCV) + asunaprevir (ASV) combination therapy has become available for patients with hepatitis C virus (HCV) serogroup 1 infection. We studied the efficacy of this therapy by focusing on the factors associated with sustained virological responses (SVR) including resistance-associated variants (RAVs) and mixed infection of different HCV genotypes. We enrolled 951 HCV serogroup 1-positive patients who received this combination therapy at our hospital or affiliated hospitals. The presence of RAVs in non-structural (NS) regions 3 and 5A was analyzed by direct sequencing. HCV genotypes were determined by PCR with genotype-specific primers targeting HCV core and NS5B regions. SVR was achieved in 91.1% of patients. Female sex, age > 70 years, and RAVs were significantly associated with non-SVR (p<0.01 for all). Propensity score-matching results among the patients without RAVs regarding sex, age, and fibrosis revealed that mixed HCV infection determined by HCV NS5B genotyping showed significantly lower SVR rates than 1B-mono infection (p=0.02). Female sex and RAVs were significant factors associated with treatment failure of this combination therapy for patients with HCV serogroup 1 infection. Mixed HCV infection other than 1B-mono infection would be useful for predicting treatment failure.

Original languageEnglish
Pages (from-to)401-406
Number of pages6
JournalActa Medica Okayama
Volume72
Issue number4
Publication statusPublished - Jan 1 2018

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Virus Diseases
Viruses
Hepacivirus
Genotype
Therapeutics
Infection
Treatment Failure
BMS-790052
asunaprevir
Propensity Score
Coinfection
Fibrosis
Polymerase Chain Reaction

Keywords

  • Asunaprevir
  • Daclatasvir
  • HCV
  • Mixed genotype
  • Serogrouping 1 infection

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Mixed HCV infection of genotype 1b and other genotypes influences non-response during daclatasvir + asunaprevir combination Therapy. / Wada, Nozomu; Ikeda, Fusao; Mori, Chizuru; Takaguchi, Koichi; Fujioka, Shin Ichi; Kobashi, Haruhiko; Morimoto, Yoichi; Kariyama, Kazuya; Sakaguchi, Kosaku; Hashimoto, Noriaki; Moriya, Akio; Kawaguchi, Mitsuhiko; Miyatake, Hirokazu; Hagihara, Hiroaki; Kubota, Junichi; Takayama, Hiroki; Takeuchi, Yasuto; Yasunaka, Tetsuya; Takaki, Akinobu; Iwasaki, Yoshiaki; Okada, Hiroyuki.

In: Acta Medica Okayama, Vol. 72, No. 4, 01.01.2018, p. 401-406.

Research output: Contribution to journalArticle

Wada, N, Ikeda, F, Mori, C, Takaguchi, K, Fujioka, SI, Kobashi, H, Morimoto, Y, Kariyama, K, Sakaguchi, K, Hashimoto, N, Moriya, A, Kawaguchi, M, Miyatake, H, Hagihara, H, Kubota, J, Takayama, H, Takeuchi, Y, Yasunaka, T, Takaki, A, Iwasaki, Y & Okada, H 2018, 'Mixed HCV infection of genotype 1b and other genotypes influences non-response during daclatasvir + asunaprevir combination Therapy', Acta Medica Okayama, vol. 72, no. 4, pp. 401-406.
Wada, Nozomu ; Ikeda, Fusao ; Mori, Chizuru ; Takaguchi, Koichi ; Fujioka, Shin Ichi ; Kobashi, Haruhiko ; Morimoto, Yoichi ; Kariyama, Kazuya ; Sakaguchi, Kosaku ; Hashimoto, Noriaki ; Moriya, Akio ; Kawaguchi, Mitsuhiko ; Miyatake, Hirokazu ; Hagihara, Hiroaki ; Kubota, Junichi ; Takayama, Hiroki ; Takeuchi, Yasuto ; Yasunaka, Tetsuya ; Takaki, Akinobu ; Iwasaki, Yoshiaki ; Okada, Hiroyuki. / Mixed HCV infection of genotype 1b and other genotypes influences non-response during daclatasvir + asunaprevir combination Therapy. In: Acta Medica Okayama. 2018 ; Vol. 72, No. 4. pp. 401-406.
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AU - Takaguchi, Koichi

AU - Fujioka, Shin Ichi

AU - Kobashi, Haruhiko

AU - Morimoto, Yoichi

AU - Kariyama, Kazuya

AU - Sakaguchi, Kosaku

AU - Hashimoto, Noriaki

AU - Moriya, Akio

AU - Kawaguchi, Mitsuhiko

AU - Miyatake, Hirokazu

AU - Hagihara, Hiroaki

AU - Kubota, Junichi

AU - Takayama, Hiroki

AU - Takeuchi, Yasuto

AU - Yasunaka, Tetsuya

AU - Takaki, Akinobu

AU - Iwasaki, Yoshiaki

AU - Okada, Hiroyuki

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N2 - Daclatasvir (DCV) + asunaprevir (ASV) combination therapy has become available for patients with hepatitis C virus (HCV) serogroup 1 infection. We studied the efficacy of this therapy by focusing on the factors associated with sustained virological responses (SVR) including resistance-associated variants (RAVs) and mixed infection of different HCV genotypes. We enrolled 951 HCV serogroup 1-positive patients who received this combination therapy at our hospital or affiliated hospitals. The presence of RAVs in non-structural (NS) regions 3 and 5A was analyzed by direct sequencing. HCV genotypes were determined by PCR with genotype-specific primers targeting HCV core and NS5B regions. SVR was achieved in 91.1% of patients. Female sex, age > 70 years, and RAVs were significantly associated with non-SVR (p<0.01 for all). Propensity score-matching results among the patients without RAVs regarding sex, age, and fibrosis revealed that mixed HCV infection determined by HCV NS5B genotyping showed significantly lower SVR rates than 1B-mono infection (p=0.02). Female sex and RAVs were significant factors associated with treatment failure of this combination therapy for patients with HCV serogroup 1 infection. Mixed HCV infection other than 1B-mono infection would be useful for predicting treatment failure.

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