TY - JOUR
T1 - The clinical features of patients with a Y93H variant of hepatitis C virus detected by a PCR invader assay
AU - Kan, Toshiki
AU - Hashimoto, Senju
AU - Kawabe, Naoto
AU - Murao, Michihito
AU - Nakano, Takuji
AU - Shimazaki, Hiroaki
AU - Nakaoka, Kazunori
AU - Ohki, Masashi
AU - Takagawa, Yuka
AU - Kurashita, Takamitsu
AU - Takamura, Tomoki
AU - Yoshioka, Kentaro
N1 - Publisher Copyright:
© 2015, Springer Japan.
PY - 2016/1/1
Y1 - 2016/1/1
N2 - 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.
AB - 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.
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U2 - 10.1007/s00535-015-1080-1
DO - 10.1007/s00535-015-1080-1
M3 - Article
C2 - 25904097
AN - SCOPUS:84953359871
SN - 0944-1174
VL - 51
SP - 63
EP - 70
JO - Journal of Gastroenterology
JF - Journal of Gastroenterology
IS - 1
ER -