title: Association of interleukin 28B and mutations in the core and NS5A region of hepatitis C virus with response to peg-interferon and ribavirin therapy.
abstract: OBJECTIVE
  Mutations in the core and NS5A region of hepatitis C virus (HCV) genotype 1b have been associated with response to interferon (IFN) therapy. Genome-wide association studies have revealed that the single-nucleotide polymorphism (SNP) of interleukin 28B (IL28B) contributes to IFN response. The aim of this study was to investigate whether the SNP of IL28B (rs8099917) and amino acid substitutions in the core and NS5A region affect the response to IFN therapy.
  
  
  METHODS
  A total of 299 patients (157 men, 142 women; mean age, 55.9 ± 10.3 years) infected with HCV genotype 1b were studied. The fibrosis stage was diagnosed as F0 (n=23), F1 (n=121), F2 (n=62), F3 (n=32) and F4 (n=7) by liver biopsy.
  
  
  RESULTS
  Of the 299 patients, 138 achieved sustained virological response (SVR). On univariate analysis, predictors of SVR were age <60 years, male gender, higher platelet count, lack of fibrosis, non-Q at core 70, mutant-type interferon sensitivity-determining region (ISDR) and IL28B genotype TT. The factors related to SVR on multivariate analysis were IL28B (P=0.0001), fibrosis (P=0.0111) and mutations in the core region70 (P=0.0267) and ISDR (P=0.0408). The best SVR was achieved in patients with non-Q70, mutant-type ISDR and T allele (74.5%), and the worst was achieved in patients with Q70, wild-type ISDR and G allele (8.1%).
  
  
  CONCLUSIONS
  The SNP of IL28B and mutations in the core region and NS5A are associated with IFN responsiveness. Both host and viral factors might be useful for predicting IFN response.
authors: Department of Gastroenterology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors: Kazuhiko
authors: K
authors: Hayashi
authors: Yoshiaki
authors: Y
authors: Katano
authors: Takashi
authors: T
authors: Honda
authors: Masatoshi
authors: M
authors: Ishigami
authors: Akihiro
authors: A
authors: Itoh
authors: Yoshiki
authors: Y
authors: Hirooka
authors: Tetsuya
authors: T
authors: Ishikawa
authors: Isao
authors: I
authors: Nakano
authors: Kentaro
authors: K
authors: Yoshioka
authors: Hidenori
authors: H
authors: Toyoda
authors: Takashi
authors: T
authors: Kumada
authors: Hidemi
authors: H
authors: Goto
mesh_terms: D000368:Aged; D019943:Amino Acid Substitution; D000998:Antiviral Agents / Q000627:therapeutic use*; D001706:Biopsy; D016009:Chi-Square Distribution; D024882:Drug Resistance, Viral / Q000235:genetics; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000187:drug effects* / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D007372:Interferons; D007378:Interleukins / Q000235:genetics*; D007564:Japan; D008103:Liver Cirrhosis / Q000188:drug therapy / Q000235:genetics / Q000276:immunology / Q000821:virology; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009154:Mutation; D018579:Patient Selection; D010641:Phenotype; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D020641:Polymorphism, Single Nucleotide; D012367:RNA, Viral / Q000097:blood; D011994:Recombinant Proteins / Q000627:therapeutic use; D012254:Ribavirin / Q000627:therapeutic use*; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D014758:Viral Core Proteins / Q000235:genetics*; D019562:Viral Load; D017361:Viral Nonstructural Proteins / Q000235:genetics*; D000095022:Interferon Lambda; D012324:RNA-Dependent RNA Polymerase
chemical_list: D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D007372:Interferons; D007378:Interleukins; D011092:Polyethylene Glycols; D012367:RNA, Viral; D011994:Recombinant Proteins; D012254:Ribavirin; D014758:Viral Core Proteins; D017361:Viral Nonstructural Proteins; C000624353:interferon-lambda, human; D000095022:Interferon Lambda; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase; C417083:peginterferon alfa-2b