title: Insulin resistance predicts sustained virological response to treatment of chronic hepatitis C independently of the IL28b rs12979860 polymorphism.
abstract: BACKGROUND
  Insulin resistance has been strongly associated with the attainment of sustained viral response (SVR) in hepatitis C patients.
  
  
  OBJECTIVE
  To determine, in a cohort of Spanish patients with chronic hepatitis C treated with peginterferon plus ribavirin (P+R), whether insulin resistance predicts SVR independently of interleukin-28B rs12979860 polymorphism.
  
  
  METHODS
  Insulin resistance was measured as [HOMA-IR = Insulin (IU/mL)*glucose (mmol/L)/22.5]. Genotype, viral load and histological fibrosis using Scheuer score were also measured. Binary logistic regression analysis was used for statistical purposes.
  
  
  RESULTS
  In a cohort of 240 patients [78% genotype 1, 24% showing advanced fibrosis, 71% high viral load (≥800 000 IU/mL), 31% IL28b genotype CC and 50% with HOMA >2] treated with P+R, 126 (53%) reached SVR. HOMA-IR index (HOMA <2: 63% vs. HOMA >2: 42%; P = 0.001 and IL28b (genotype CC: 68% vs. genotype CT/TT: 45%; P = 0.002) were significantly associated with SVR. In multivariable logistic regression analysis in the overall cohort, variables independently associated were: viral genotype OR: 0.29 (95% CI: 0.11-0.78), P = 0.01; fibrosis OR: 1.62 (95% CI: 1.22-2.16), P = 0.001; HOMA-IR OR: 1.22 (95% CI: 1.02-1.47), P = 0.03; and IL28B genotype OR: 2.43 (95% CI: 1.45-4.07), P = 0.001. The analyses also showed that degree of steatosis, HOMA-IR >2, mild fibrosis and IL28B CC genotype were significantly related to SVR in patients infected with HCV genotypes 1&4, but not in those with genotypes 2&3. No differences were seen in glucose, insulin level or HOMA-IR index segregated according to IL28B genotypes.
  
  
  CONCLUSIONS
  Our results suggest that insulin resistance, fibrosis stage and IL28B polymorphisms were independent variables associated with sustained viral response.
authors.affiliation: UCM Digestive Diseases and CIBERehd, Hospital Universitario de Valme, Sevilla, Spain.
authors.forename: J A
authors.initials: JA
authors.lastname: Del Campo
authors.forename: J
authors.initials: J
authors.lastname: Ampuero
authors.forename: L
authors.initials: L
authors.lastname: Rojas
authors.forename: M
authors.initials: M
authors.lastname: Conde
authors.forename: A
authors.initials: A
authors.lastname: Rojas
authors.forename: M
authors.initials: M
authors.lastname: Maraver
authors.forename: R
authors.initials: R
authors.lastname: Millán
authors.forename: M
authors.initials: M
authors.lastname: García-Valdecasas
authors.forename: J R
authors.initials: JR
authors.lastname: García-Lozano
authors.forename: M F
authors.initials: MF
authors.lastname: González-Escribano
authors.forename: M
authors.initials: M
authors.lastname: Romero-Gómez
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D001786:Blood Glucose / Q000032:analysis; D015331:Cohort Studies; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D060005:Genotyping Techniques; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000235:genetics; D006801:Humans; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000235:genetics*; D016898:Interferon-alpha / Q000627:therapeutic use; D007372:Interferons; D007378:Interleukins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000627:therapeutic use; D020641:Polymorphism, Single Nucleotide; D011994:Recombinant Proteins / Q000627:therapeutic use; D012044:Regression Analysis; D012254:Ribavirin / Q000627:therapeutic use; D016896:Treatment Outcome; D019562:Viral Load; D000095022:Interferon Lambda
chemical_list: D000998:Antiviral Agents; D001786:Blood Glucose; D007328:Insulin; 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