title: Role of IL28B for chronic hepatitis C treatment toward personalized medicine.
abstract: Genome-wide association studies recently revealed 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, as well as with spontaneous clearance of HCV. Subsequent reports revealed that IL28B genotypes also affect treatment efficacy in chronic infection with other HCV genotypes. Furthermore, there have been several reports that implicate IL28B genotypes in inflammatory status, progression of fibrosis and adverse clinical outcomes in chronic hepatitis C (CHC). Therapy of CHC recently entered a new era with the deployment of direct-acting antivirals. These include nonstructural 3/4A protease inhibitors which have shown promise in combination with PEG-IFN/RBV in several clinical trials. IFN-free therapy is expected to be useful especially in 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 or IFN-free regimens. On the other hand the mechanism of the effect of IL28B on HCV infection has not yet been elucidated. Recently, it was shown that the 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 IL28B genotypes, 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 also useful for personalized CHC treatment in the forthcoming era of direct-acting antivirals.
authors: Department of Virology, Liver Unit, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan; Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan; Infectious Disease and Immunogenetics Section, Department of Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda, Maryland, United States.
authors: Kentaro
authors: K
authors: Matsuura
authors: Tsunamasa
authors: T
authors: Watanabe
authors: Yasuhito
authors: Y
authors: Tanaka
mesh_terms: D000998:Antiviral Agents / Q000627:therapeutic use*; D055106:Genome-Wide Association Study; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000235:genetics* / Q000821:virology; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D007372:Interferons; D007378:Interleukins / Q000235:genetics*; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D011110:Polymorphism, Genetic; D057285:Precision Medicine; D011994:Recombinant Proteins / Q000627:therapeutic use; D012254:Ribavirin / Q000627:therapeutic use; D016896:Treatment Outcome; D000095022:Interferon Lambda
chemical_list: D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D007372:Interferons; D007378:Interleukins; D011092:Polyethylene Glycols; D011994:Recombinant Proteins; D012254:Ribavirin; C000624353:interferon-lambda, human; D000095022:Interferon Lambda; C579163:IFNL4 protein, human; C417083:peginterferon alfa-2b; C100416:peginterferon alfa-2a
keywords: direct-acting antiviral (DAA); genome-wide association study (GWAS); hepatitis C virus (HCV); interleukin 28B (IL28B)