title: Insulin resistance undermines the advantages of IL28B polymorphism in the pegylated interferon alpha-2b and ribavirin treatment of chronic hepatitis C patients with genotype 1.
abstract: OBJECTIVE
  Recent studies have suggested that insulin resistance exerts a strong influence on chronic hepatitis C virus (HCV) infection. We analyzed pretreatment factors useful for predicting sustained virological response (SVR), especially interleukin (IL) 28B polymorphism and Homeostasis Model Assessment of Insulin Resistance (HOMA-IR).
  
  
  METHODS
  This cohort study consisted of 328 chronic hepatitis C patients with HCV genotype 1 who were treated for 48 weeks with pegylated interferon (PegIFN) α-2b and ribavirin (RBV). Genotyping of the polymorphisms in the IL28B gene region (rs8099917) on chromosome 19 was performed on DNA collected from each patient.
  
  
  RESULTS
  No significant difference in IL28B genotype distribution was found according to HOMA-IR. Multivariate analysis identified the IL28B TT genotype (OR=5.97, 95% CI 2.15-16.55, p=0.0006) and the baseline HOMA-IR (OR=0.65, 95% CI 0.48-0.87, p=0.0044) as significant, independent pretreatment predictors of SVR. Receiver operating characteristic analyses to determine the optimal threshold values of HOMA-IR for predicting SVR showed that the areas under the curve (AUC) were high for both IL28B TT (AUC=0.774, HOMA-IR cut-off value: 2.45) and IL28B TG/GG genotypes (AUC=0.772, HOMA-IR cut-off value: 1.55).
  
  
  CONCLUSIONS
  For HCV genotype 1, both IL28B and baseline HOMA-IR are independent pretreatment predictors of SVR in patients treated with PegIFNα-2b and RBV. Insulin resistance undermines the advantages of IL28B polymorphism to obtain SVR.
authors.affiliation: Department of General Internal Medicine, Kyushu University Hospital, Fukuoka, Japan.
authors.forename: Eiichi
authors.initials: E
authors.lastname: Ogawa
authors.forename: Norihiro
authors.initials: N
authors.lastname: Furusyo
authors.forename: Masayuki
authors.initials: M
authors.lastname: Murata
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Ikezaki
authors.forename: Takeshi
authors.initials: T
authors.lastname: Ihara
authors.forename: Takeo
authors.initials: T
authors.lastname: Hayashi
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Toyoda
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Taniai
authors.forename: Kyoko
authors.initials: K
authors.lastname: Okada
authors.forename: Mosaburo
authors.initials: M
authors.lastname: Kainuma
authors.forename: Jun
authors.initials: J
authors.lastname: Hayashi
mesh_terms: D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use*; D019540:Area Under Curve; D015331:Cohort Studies; D016001:Confidence Intervals; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000235:genetics*; D006706:Homeostasis; D006801:Humans; D007333:Insulin Resistance; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D007372:Interferons; D007378:Interleukins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D015999:Multivariate Analysis; D016017:Odds Ratio; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D020641:Polymorphism, Single Nucleotide; D012372:ROC Curve; 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; C417083:peginterferon alfa-2b