Genetics of IL28B and HCV--response to infection and treatment.
The IL28B locus attracted the attention of HCV researchers after a series of genome-wide association studies independently identified a strong association between common IL28B polymorphisms and the outcome of PEG-IFN-α plus ribavirin combination therapy in patients chronically infected with HCV genotype 1. This association was subsequently replicated for other HCV genotypes and has been linked to spontaneous eradication of HCV, development of steatosis and biochemical changes (such as altered levels of γ-glutamyl transpeptidase and LDL). Despite the introduction of direct-acting antiviral drugs, IL28B genetics are likely to play a part in patient selection and treatment decisions-moving towards a personalized approach to therapy. In HCV-infected patients with the so-called favourable IL28B genotype (rs12979860 CC; associated with better treatment response), hepatic expression levels of IL28B and interferon-stimulated genes seem to be reduced at baseline, but are induced more strongly after IFN-α administration, perhaps resulting in more effective elimination of the virus. Clarification of the mechanisms underlying these biological phenomena will lead to improved understanding of the antiviral effects of IFN-λ and, ideally, to the development of better therapies against HCV infection. This Review summarizes current understanding of the role of IL28B in HCV infection and response to therapy.
Department of Gastroenterology and Metabolism, Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku Hiroshima 734-8551, Japan.
C Nelson
CN
Hayes
Michio
M
Imamura
Hiroshi
H
Aikata
Kazuaki
K
Chayama
D000998:Antiviral Agents / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D006526:Hepatitis C / Q000188:drug therapy* / Q000235:genetics*; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use; D007372:Interferons; D007378:Interleukins / Q000235:genetics*; D010597:Pharmacogenetics; D011092:Polyethylene Glycols / Q000627:therapeutic use; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D057285:Precision Medicine; D011994:Recombinant Proteins / Q000627:therapeutic use; D012254:Ribavirin / Q000627:therapeutic use; D016896:Treatment Outcome; D000095022:Interferon Lambda
D000998:Antiviral Agents; D016898:Interferon-alpha; D007372:Interferons; D007378:Interleukins; D011092:Polyethylene Glycols; D011994:Recombinant Proteins; D012254:Ribavirin; C000624353:interferon-lambda, human; D000095022:Interferon Lambda; C100416:peginterferon alfa-2a