title: Insulin resistance impairs sustained response rate to peginterferon plus ribavirin in chronic hepatitis C patients.
abstract: OBJECTIVE
  We evaluated the effect of insulin resistance and viral factors on sustained virological response in patients with chronic hepatitis C treated with peginterferon plus ribavirin.
  
  
  METHODS
  Patients (n=159; 94 men; age, 41.7 +/- 11.1 years) with chronic hepatitis C (genotype 1, n=113; non-1 genotype, n=46) received treatment with interferon plus ribavirin. Serum levels of leptin and insulin were measured, and the insulin resistance index (HOMA-IR: homeostasis model of assessment) and body mass index were calculated.
  
  
  RESULTS
  A sustained virological response was associated with lower age, insulin resistance index, body mass index, and gamma-glutamyltranspeptidase and serum leptin levels. There was no association with viral load, sex, type of interferon, or cholesterol levels. A sustained virological response was achieved in 43.4% (46/113) of genotype 1 and 89% (32/36) of genotype 2 and 3 (P=.0001) patients. Necroinflammatory activity and steatosis were not associated with the sustained virological response rate. Multivariate regression analysis indicated that the independent variables related to sustained virological response were genotype (odds ratio, 3.57; 95% confidence interval, 1.49-8.3; P=.001), insulin resistance index (odds ratio, 1.82; 95% confidence interval, 1.08-3.06; P=.012), and fibrosis (odds ratio, 1.36; 95% confidence interval, 1.01-1.84; P=.029). A sustained virological response in patients with genotype 1 and insulin resistance (HOMA-IR > 2) occurred in 23 of 70 (32.8%; 95% confidence interval, 21.9%-43.9%) patients, vs. 26 of 43 (60.5%; 95% confidence interval, 45.9%-75.1%) genotype 1 patients without insulin resistance (P=.007; odds ratio, 3.12, 95% confidence interval, 1.42-6.89).
  
  
  CONCLUSIONS
  Insulin resistance, fibrosis, and genotype are independent predictors of the response to antiviral therapy in chronic hepatitis C patients treated with peginterferon plus ribavirin.
authors.affiliation: Hepatology Unit, Hospital Universitario de Valme, Sevilla, Spain. mromerog@supercable.es
authors.forename: Manuel
authors.initials: M
authors.lastname: Romero-Gómez
authors.forename: Maria
authors.initials: M
authors.lastname: Del Mar Viloria
authors.forename: Raúl J
authors.initials: RJ
authors.lastname: Andrade
authors.forename: Javier
authors.initials: J
authors.lastname: Salmerón
authors.forename: Moisés
authors.initials: M
authors.lastname: Diago
authors.forename: Conrado M
authors.initials: CM
authors.lastname: Fernández-Rodríguez
authors.forename: Raquel
authors.initials: R
authors.lastname: Corpas
authors.forename: Marina
authors.initials: M
authors.lastname: Cruz
authors.forename: Lourdes
authors.initials: L
authors.lastname: Grande
authors.forename: Luis
authors.initials: L
authors.lastname: Vázquez
authors.forename: Paloma
authors.initials: P
authors.lastname: Muñoz-De-Rueda
authors.forename: Pilar
authors.initials: P
authors.lastname: López-Serrano
authors.forename: Ana
authors.initials: A
authors.lastname: Gila
authors.forename: María L
authors.initials: ML
authors.lastname: Gutiérrez
authors.forename: Celia
authors.initials: C
authors.lastname: Pérez
authors.forename: Angela
authors.initials: A
authors.lastname: Ruiz-Extremera
authors.forename: Emilio
authors.initials: E
authors.lastname: Suárez
authors.forename: Jesús
authors.initials: J
authors.lastname: Castillo
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use*; D015331:Cohort Studies; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D019698:Hepatitis C, Chronic / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology* / Q000821:virology; D006801:Humans; D007333:Insulin Resistance; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D008103:Liver Cirrhosis / Q000821:virology; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D011994:Recombinant Proteins; D012254:Ribavirin / Q000627:therapeutic use*; D016896:Treatment Outcome; D019562:Viral Load; D014766:Viremia / Q000503:physiopathology
chemical_list: D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C417083:peginterferon alfa-2b; C100416:peginterferon alfa-2a