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Association of interferon lambda polymorphisms with elevated baseline viral loads in chronic hepatitis C virus genotype 6 infection

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Abstract

Globally, hepatitis C virus (HCV) is one of the major causes of hepatocellular carcinoma and liver cirrhosis. For clinical decision making, genetic variation in the interferon-λ (IFNL) cluster has been utilised as a baseline predictor of natural and interferon-based treatment-induced viral clearance. In Vietnam, where HCV genotypes 1 (g1) and g6 predominate, no prior studies have been conducted investigating associations of IFNL3/4 polymorphisms with spontaneous clearance (SC) or HCV viral load (VL) in chronic infection. In this study, we have investigated the host genetic variations in IFNL loci to determine the association of IFNL3/4 polymorphisms with HCV SC and baseline VLs in a Vietnamese HCV-seropositive cohort. The majority of the cohort harboured major homozygous polymorphisms in IFNL3/4 cluster (i.e. rs12979860-CC: 82.7%; rs8099917-TT: 84.8% and rs368234815-TT/TT: 85.5%) and the SC rates in these groups were 15.8%, 16.3% and 15.7%, respectively. In the minor allele groups, the resolution rates were lower (12% in rs12979860 non-CC, 9.1% in rs8099917 non-TT and 9.5% in rs368234815 non-TT/TT). Furthermore, in individuals harbouring minor alleles, females achieved higher SC rates than males. HCV g6-infected rs12979860 major homozygous individuals had significantly higher viral loads than individuals with minor alleles (CC: 6.56 log IU/ml vs. non-CC: 5.66 log IU/ml; P = 0.021). The association between IFNL3/4 genotypes with elevated HCV VL observed in HCV g6-infected individuals may have implications for the progression of liver disease in Southeast Asian countries where this viral genotype predominates and therefore warrants further studies.

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Acknowledgements

This study was performed under the auspices of the Ireland Vietnam Blood-Borne Virus Initiative (IVVI). The authors would like to thank the patients and colleagues in Bach Mai hospital and to acknowledge the technical assistance from the experts in the National Virus Reference Laboratory in University College Dublin and all staff involved in specimen collection and testing performance in the Laboratory of Molecular Diagnostics, National Institute of Hygiene and Epidemiology, Hanoi.

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Authors and Affiliations

  1. Laboratory of Molecular Diagnostics, National Institute of Hygiene and Epidemiology, Hanoi, Vietnam

    Linh Thuy Nguyen & Lan Anh Nguyen

  2. Department of Infectious Diseases, Bach Mai Hospital, Hanoi, Vietnam

    Dzung Van Nguyen

  3. Global Station for Zoonosis Control, Global Institution for Collaborative Research and Education (GI-CoRE), Hokkaido University, N20, W10, Kita-ku, Sapporo, 001-0020, Japan

    Linh Thuy Nguyen, Michael J. Carr, William W. Hall & Lan Anh Nguyen

  4. National Virus Reference Laboratory, University College Dublin, Dublin, Ireland

    Michael J. Carr & William W. Hall

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  1. Linh Thuy Nguyen
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Correspondence to Linh Thuy Nguyen.

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Ethical approval and consent forms

Ethical approval (No. 13 IRB, 29 June 2012) was obtained from the National Institute of Hygiene and Epidemiology, Hanoi. All subjects signed an informed consent form prior to participation in the study.

Funding

Financial supports included Research grant No. 106.16-2011.14 from the National Foundation for Science and Technology (NAFOSTED), Vietnam and Atlantic Philanthropies Director/Employee Designated Gift Fund.

Conflict of interest

The authors declare that they have no conflict of interest.

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Handling Editor: Michael Carpenter.

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Nguyen, L.T., Van Nguyen, D., Carr, M.J. et al. Association of interferon lambda polymorphisms with elevated baseline viral loads in chronic hepatitis C virus genotype 6 infection. Arch Virol 163, 115–124 (2018). https://doi.org/10.1007/s00705-017-3583-y

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  • DOI: https://doi.org/10.1007/s00705-017-3583-y

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