The clinical features of patients with a Y93H variant of hepatitis C virus detected by a PCR invader assay - PubMed (original) (raw)

doi: 10.1007/s00535-015-1080-1. Epub 2015 Apr 24.

Senju Hashimoto 1, Naoto Kawabe 1, Michihito Murao 1, Takuji Nakano 1, Hiroaki Shimazaki 1, Kazunori Nakaoka 1, Masashi Ohki 1, Yuka Takagawa 1, Takamitsu Kurashita 1, Tomoki Takamura 1, Kentaro Yoshioka 2

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The clinical features of patients with a Y93H variant of hepatitis C virus detected by a PCR invader assay

Toshiki Kan et al. J Gastroenterol. 2016 Jan.

Abstract

Background: Resistance-associated variants (RAVs) reduce the efficacy of interferon (IFN)-free therapy with asunaprevir and daclatasvir for patients infected with hepatitis C virus (HCV) genotype 1b. The characteristics of patients with an L31 or a Y93 variant in the nonstructural 5A region detected by a polymerase chain reaction invader assay were investigated.

Methods: In total, 201 patients with HCV genotype 1b were examined for L31F/M/V variants or a Y93H variant by the polymerase chain reaction invader assay.

Results: L31M and Y93H variants were detected in 4.6 and 21.4 % of patients, respectively. Patients with an L31M variant had no significant characteristics. Patients with a Y93H variant had significantly higher HCV RNA levels (6.5 ± 0.5 log copies per milliliter vs 6.1 ± 0.7 log copies per milliliter, p = 0.0002), higher frequency of mutant type of the IFN-sensitivity-determining region (88.4 % vs 71.7 %, p = 0.0251), and higher frequency of TT genotype at rs8099917 of IL28B (91.7 % vs 54.3 %, p < 0.0001) than those with Y93 wild-type strains. Multivariate analysis identified HCV RNA levels [odds ratio (OR) 3.72, 95 % confidence interval (CI) 1.71-8.06, p = 0.0009] and TT genotype at rs8099917 (OR 7.45, 95 % CI 2.11-26.4, p = 0.0018) as factors associated with the presence of a Y93H variant.

Conclusion: The presence of a Y93H variant was associated with higher HCV RNA levels and TT genotype at rs8099917 of IL28B. Thus, patients with a Y93H variant may be ideal candidates for IFN-based therapy rather than IFN-free therapy, although the high viral load of these patients may reduce the response rate of IFN-based therapy.

Keywords: Direct-acting antiviral agents; Hepatitis C virus; IL28B; PCR invader assay; Resistance-associated variants.

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