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IL28B Polymorphisms and Treatment of Hepatitis C

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Abstract

Recently, single-nucleotide polymorphisms near the IL28B gene have been identified as important in predicting treatment response and spontaneous clearance of the hepatitis C virus (HCV). In the less than 12 months since the initial genetic discoveries, our knowledge base has rapidly expanded regarding the significance of the IL28B polymorphism in a variety of clinical settings. For genotype 1 HCV infection, it is clear that IL28B genotype has an important role in the prediction of treatment-induced and spontaneous clearance. This association remains important in the HIV/HCV-coinfected population. Host genotype adds further discriminatory information in HCV genotype 2/3 infection. IL28B genotype may remain significant with direct-acting antiviral therapy, although further studies are needed for antiviral agents and novel immunotherapy. Information on IL28B genotype improves treatment prediction with standard of care and will integrate with existing pretreatment clinical factors and measures of on-treatment response. Pretreatment knowledge of sustained viral response may help to reshape treatment regimens of the future with the possibility of reducing therapy duration and improving tolerability, safety, and efficacy.

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Acknowledgments

The authors thank Reinhold Muller for comments on an early draft. P. Clark and A. Thompson received funding support from the Duke Clinical Research Institute, the Richard B. Boebel Family Fund, and the Gastroenterology Society of Australia. A. Thompson received funding from the National Health and Medical Research Council of Australia and the Royal Australasian College of Physicians.

Disclosure

Conflicts of interest: P. Clark—none; A. Thompson—coinventor of a patent application based on the IL28B finding; A. Muir—research grants from Abbott, Anadys, Gilead, Glaxo SmithKline, Idera, Medtronic, Merck, Pfizer, Pharmasset, Roche, Scynexis, Santaris, Three Rivers Pharma, Vertex, and Zymogenetics, and consulting services for Bristol-Myers Squibb, Merck, Pharmasset, Salix, Santaris, Vertex, and Zymogenetics.

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Correspondence to Andrew J. Muir.

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Clark, P.J., Thompson, A.J.V. & Muir, A.J. IL28B Polymorphisms and Treatment of Hepatitis C. Curr Hepatitis Rep 10, 70–78 (2011). https://doi.org/10.1007/s11901-010-0061-3

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