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Hepatitis C Virus II pp 225–241Cite as

Host Genetics and Responses to Antiviral Therapy in Chronic Hepatitis C

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Abstract

Genome-wide association studies (GWAS) have revealed recently that certain interleukin-28B (IL28B) polymorphisms are strongly associated with responses to pegylated interferon (PEG-IFN) and ribavirin (RBV) therapy in patients chronically infected with hepatitis C virus (HCV) genotype 1. Subsequent reports revealed that these IL28B polymorphisms also affect treatment efficacy in chronic infection with other HCV genotypes. Therapy of chronic hepatitis C (CHC) recently has entered a new era with the availability of direct-acting antiviral agents (DAAs). These include non-structural 3/4A protease inhibitors which have shown promise in combination with PEG-IFN/RBV in several clinical trials, as well as in clinical practice. IFN-free therapy is expected to be useful especially for IFN-resistant patients and may become the standard of care in the future. Several clinical trials have revealed an association between IL28B genotype and treatment efficacy in triple therapy and in some interferon-free regimens. Recently, it was shown that a polymorphism of IFN-lambda 4 (IFNL4) is in high linkage disequilibrium with that of near IL28B and more strongly associated with spontaneous or treatment-induced HCV clearance than the IL28B polymorphisms, especially in individuals of African ancestry. This finding provides new insights into the genetic regulation of HCV clearance and its clinical management. IL28B genotyping will be useful for personalized treatment of CHC in the forthcoming era of DAAs.

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Financial Support

This work was supported in part by a grant-in-aid from the Ministry of Health, Labour and Welfare of Japan, and a grant-in-aid from the Ministry of Education, Culture, Sports, Science and Technology.

Conflicts of Interests

Yasuhito Tanaka has research contracts with MSD (Merck Sharp & Dohme), Chugai Pharmaceutical Co. Ltd and Bristol-Myers Squibb.

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Authors and Affiliations

  1. Department of Virology, Liver Unit, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan

    Yasuhito Tanaka M.D., Ph.D.

  2. The Research Center for Hepatitis & Immunology, National Center for Global Health and Medicine, 1-7-1 Kohnodai, Ichikawa, Chiba, 272-8516, Japan

    Masashi Mizokami M.D., Ph.D.

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  1. Yasuhito Tanaka M.D., Ph.D.
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Correspondence to Masashi Mizokami M.D., Ph.D. .

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Editors and Affiliations

  1. National Institute of Infectious Disease , Tokyo, Japan

    Tatsuo Miyamura

  2. Departments of Medicine and Microbiology, The Univ of N Carolina at Chapel Hill Departments of Medicine and Microbiology, Chapel Hill, North Carolina, USA

    Stanley M. Lemon

  3. Center for Vaccines and Immunity, The Research Institute at Nationwide Children's Hospital , Ohio, USA

    Christopher M. Walker

  4. National Institute of Infectious Disease, Tokyo, Japan

    Takaji Wakita

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Tanaka, Y., Mizokami, M. (2016). Host Genetics and Responses to Antiviral Therapy in Chronic Hepatitis C. In: Miyamura, T., Lemon, S., Walker, C., Wakita, T. (eds) Hepatitis C Virus II. Springer, Tokyo. https://doi.org/10.1007/978-4-431-56101-9_8

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