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.
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Acknowledgments
This study was supported by MEXT-Supported Program for the Strategic Research Foundation at Private Universities of the Japanese government and by the Ministry of Health, Labour and Welfare of the Japanese government. The authors thank Makiko Shimazaki and Akie Tsuda from the Department of Liver, Biliary Tract, and Pancreas Diseases, Fujita Health University, for assisting with data collection and analysis.
Conflict of interest
Kentaro Yoshioka received a research grant from MSD KK, serves a consultant to Sanwa Kagaku Kenkyusho Co., Ltd., and received lecture fees from Bristol-Myers KK. Naoto Kawabe received a research grant from Bristol-Myers KK.
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Kan, T., Hashimoto, S., Kawabe, N. et al. The clinical features of patients with a Y93H variant of hepatitis C virus detected by a PCR invader assay. J Gastroenterol 51, 63–70 (2016). https://doi.org/10.1007/s00535-015-1080-1
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DOI: https://doi.org/10.1007/s00535-015-1080-1