title: Association of IL28B variants with response to pegylated-interferon alpha plus ribavirin combination therapy reveals intersubgenotypic differences between genotypes 2a and 2b.
abstract: Genetic polymorphisms of the interleukin 28B (IL28B) locus are associated closely with outcomes of pegylated-interferon (PEG-IFN) plus ribavirin (RBV) combination therapy. The aim of this study was to investigate the relationship between IL28B polymorphism and responses to therapy in patients infected with genotype 2. One hundred twenty-nine chronic hepatitis C patients infected with genotype 2, 77 patients with genotype 2a and 52 patients with genotype 2b, were analyzed. Clinical and laboratory parameters, including genetic variation near the IL28B gene (rs8099917), were assessed. Drug adherence was monitored in each patient. Univariate and multivariate statistical analyses of these parameters and clinical responses were carried out. Univariate analyses showed that a sustained virological response was correlated significantly with IL28B polymorphism, as well as age, white blood cell and neutrophil counts, adherence to RBV, and rapid virological response. Subgroup analysis revealed that patients infected with genotype 2b achieved significantly lower rapid virological response rates than those with genotype 2a. Patients with the IL28B-major allele showed higher virus clearance rates at each time point than those with the IL28B-minor allele, and the differences were more profound in patients infected with genotype 2b than those with genotype 2a. Furthermore, both rapid and sustained virological responses were associated significantly with IL28B alleles in patients with genotype 2b. IL28B polymorphism was predictive of PEG-IFN plus RBV combination treatment outcomes in patients infected with genotype 2 and, especially, with genotype 2b. In conclusion, IL-28B polymorphism affects responses to PEG-IFN-based treatment in difficult-to-treat HCV patients.
authors.affiliation: Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan. nsakamoto.gast@tmd.ac.jp
authors.forename: Naoya
authors.initials: N
authors.lastname: Sakamoto
authors.forename: Mina
authors.initials: M
authors.lastname: Nakagawa
authors.forename: Yasuhito
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Yuko
authors.initials: Y
authors.lastname: Sekine-Osajima
authors.forename: Mayumi
authors.initials: M
authors.lastname: Ueyama
authors.forename: Masayuki
authors.initials: M
authors.lastname: Kurosaki
authors.forename: Nao
authors.initials: N
authors.lastname: Nishida
authors.forename: Akihiro
authors.initials: A
authors.lastname: Tamori
authors.forename: Nishimura-Sakurai
authors.initials: NS
authors.lastname: Yuki
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Itsui
authors.forename: Seishin
authors.initials: S
authors.lastname: Azuma
authors.forename: Sei
authors.initials: S
authors.lastname: Kakinuma
authors.forename: Shuhei
authors.initials: S
authors.lastname: Hige
authors.forename: Yoshito
authors.initials: Y
authors.lastname: Itoh
authors.forename: Eiji
authors.initials: E
authors.lastname: Tanaka
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Hiasa
authors.forename: Namiki
authors.initials: N
authors.lastname: Izumi
authors.forename: Katsushi
authors.initials: K
authors.lastname: Tokunaga
authors.forename: Masashi
authors.initials: M
authors.lastname: Mizokami
authors.forename: Mamoru
authors.initials: M
authors.lastname: Watanabe
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000008:administration & dosage*; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage*; D007372:Interferons; D007378:Interleukins / Q000235:genetics*; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000008:administration & dosage*; D011110:Polymorphism, Genetic; D011994:Recombinant Proteins; D012254:Ribavirin / Q000008:administration & dosage*; 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; C417083:peginterferon alfa-2b; C100416:peginterferon alfa-2a