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Prevalence of NS5B resistance-associated variants in treatment-naïve Asian patients with chronic hepatitis C

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Abstract

There is little information on the association between baseline non-structural protein (NS) 5b resistance-associated variants (RAVs) and treatment failure in hepatitis C patients. This study examined the frequencies of natural hepatitis C virus (HCV) NS5B resistance-associated variants (RAVs) in an Asian cohort. Samples from Asian HCV patients enrolled between October 2009 and September 2014 were analyzed for NS5B RAVs within the region from amino acid 230 to 371. Serum samples were tested by PCR genotyping, with sequence alignment performed using the neighbor-joining method. NS5B was detected by Sanger sequencing followed by Geno2pheno analysis. NS5B RAVs were detected in 80.52% (1199/1489) of patients; 68.4% (1019/1489) and 79.7% (1186/1489) were associated with resistance to sofosbuvir (SOF) and dasabuvir (DSV), respectively. These RAVs were present in 95% (1004/1058) of genotype 1b patients. When genotypes 1b and 2a were compared, SOF-associated RAVs were detected at a higher frequency in genotype 1b (94.8% [1004/1058] vs. 2.9% [9/309]; χ2 = 1054.433, P < 0.001), C316H/N was more common in genotype 1b (94.7% [1002/1058] vs. 0% [0/309]; χ2 = 1096.014, P < 0.001), M289F/L/I/W/V had a higher frequency in genotype 2a (0.7% [7/309] vs. 2.3% [7/1058]; χ2 = 4.589, P = 0.032), DSV-associated RAVs were most often found in genotype 1b (95.0% [1005/1058] vs. 40.1% 124/309]; χ2 = 500.577, P < 0.001), and frequency of C316Y/H/N/W was higher in genotype 1b (94.7% [1002/1058] vs. 0% [0/309]; χ2 = 1096.014, P < 0.001). In conclusion, baseline SOF and DSV RAVs are common in Asian HCV patients and predominantly occur in genotype 1b.

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Acknowledgements

This study was funded by the Special Fund for High-level Health Technical Personnel Development in Beijing Municipal Health System (Grant no. 2016-108). The authors thank the research coordinators and physicians at the Third Division of the Center of Liver Diseases in the Department of Medicine, Ditan Hospital, for their support of the study. Drs. Pan, Yang, and Xing contributed to the study design. Dr. Yang performed the statistical analyses. Dr. Pan wrote the manuscript and revised the draft with input from all co-authors, performed a critical review of the study, communicated with the journal, and addressed comments from reviewers. Drs. Yang, Xing, Feng, Ju, Li, Chen, Liu, Wang, Ou, and Cheng performed experiments and collected data. Drs. Xing and Yang supervised the data collection. Dr. Calvin Pan, guarantor of this article, submitted the manuscript on behalf of all authors after the aforementioned authors approved its final version.

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Author notes

  1. Co-first authors: Song Yang and Huichun Xing.

Authors and Affiliations

  1. The Third Division of the Center of Liver Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, China

    Song Yang, Huichun Xing, Shenghu Feng, Wei Ju, Xiaomei Wang, Weini Ou & Jun Cheng

  2. Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, China

    Shunai Liu

  3. Division of Gastroenterology and Hepatology, Department of Medicine, NYU Langone Medical Center, New York University School of Medicine, 132-21 41st Ave, Flushing, New York, 11355, NY, USA

    Calvin Q. Pan

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  1. Song Yang
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Correspondence to Calvin Q. Pan.

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Funding

This study was funded by the Special Fund for High-level Health Technical Personnel Development in Beijing Municipal Health System (Grant no. 2016-108).

Conflict of interest

Dr. Calvin Pan has the following financial relationships to disclose: he has received research grants from Gilead and Merck and serves as a consultant and advisor or speaker for AbbVie, Alexion, Allergan, Gilead Sciences, Salix Pharmaceuticals, and Synergy. None of the other coauthors has any conflicts of interest to disclose.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

Informed consent

The study was approved by the Institutional Review Board of our institution (no. JDL 2017-15-03) and the need for informed consent was waived.

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Handling Editor: Michael A. Purdy.

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Yang, S., Xing, H., Feng, S. et al. Prevalence of NS5B resistance-associated variants in treatment-naïve Asian patients with chronic hepatitis C. Arch Virol 163, 467–473 (2018). https://doi.org/10.1007/s00705-017-3640-6

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  • DOI: https://doi.org/10.1007/s00705-017-3640-6

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