title: Viral clearance is associated with improved insulin resistance in genotype 1 chronic hepatitis C but not genotype 2/3.
abstract: OBJECTIVE
  Genotype-specific associations between hepatitis C virus (HCV) and insulin resistance (IR) have been described, but a causal relationship remains unclear. This study investigated the association between a sustained virological response (SVR) and IR after chronic HCV therapy.
  
  
  METHODS
  2255 treatment-naive patients with chronic HCV genotype 1 or 2/3 were enrolled in two phase 3 trials of albinterferon alpha-2b versus pegylated interferon alpha-2a for 48 or 24 weeks, respectively. IR was measured before treatment and 12 weeks after treatment using homeostasis model assessment (HOMA)-IR.
  
  
  RESULTS
  Paired HOMA-IR measurements were available in 1038 non-diabetic patients (497 with genotype 1; 541 with genotype 2/3). At baseline the prevalence of HOMA-IR >3 was greater in patients with genotype 1 than 2/3 (33% vs 27%; p=0.048). There was a significant reduction in the prevalence of IR in patients with genotype 1 achieving SVR (δ 10%; p<0.001), but not in genotype 1 non-responders or those with genotype 2/3. Multivariate analysis indicated that SVR was associated with a significant reduction in mean HOMA-IR in patients with genotype 1 (p=0.004), but not in those with genotype 2/3, which was independent of body mass index, alanine transaminase, γ-glutamyl transpeptidase and lipid level changes.
  
  
  CONCLUSIONS
  SVR is associated with a reduction in HOMA-IR in patients with HCV genotype 1 but not in those with genotype 2/3. Genotype 1 may have a direct effect on the development of IR, independent of host metabolic factors, and may be partially reversed by viral eradication.
authors.affiliation: Duke Clinical Research Institute, Duke University Medical Center, P O Box 17969, Durham, NC 27715, USA. alexander.thompson@svhm.org.au
authors.forename: Alexander J
authors.initials: AJ
authors.lastname: Thompson
authors.forename: Keyur
authors.initials: K
authors.lastname: Patel
authors.forename: Wan-Long
authors.initials: WL
authors.lastname: Chuang
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Lawitz
authors.forename: Maribel
authors.initials: M
authors.lastname: Rodriguez-Torres
authors.forename: Vinod K
authors.initials: VK
authors.lastname: Rustgi
authors.forename: Robert
authors.initials: R
authors.lastname: Flisiak
authors.forename: Stephen
authors.initials: S
authors.lastname: Pianko
authors.forename: Moises
authors.initials: M
authors.lastname: Diago
authors.forename: Sanjeev
authors.initials: S
authors.lastname: Arora
authors.forename: Graham R
authors.initials: GR
authors.lastname: Foster
authors.forename: Michael
authors.initials: M
authors.lastname: Torbenson
authors.forename: Yves
authors.initials: Y
authors.lastname: Benhamou
authors.forename: David R
authors.initials: DR
authors.lastname: Nelson
authors.forename: Mark S
authors.initials: MS
authors.lastname: Sulkowski
authors.forename: Stefan
authors.initials: S
authors.lastname: Zeuzem
authors.forename: Erik
authors.initials: E
authors.lastname: Pulkstenis
authors.forename: G Mani
authors.initials: GM
authors.lastname: Subramanian
authors.forename: John G
authors.initials: JG
authors.lastname: McHutchison
mesh_terms: D000328:Adult; D000418:Albumins / Q000627:therapeutic use; D000998:Antiviral Agents / Q000627:therapeutic use; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics* / Q000302:isolation & purification; D019698:Hepatitis C, Chronic / Q000150:complications / Q000188:drug therapy / Q000821:virology*; D006801:Humans; D007333:Insulin Resistance; D016898:Interferon-alpha / Q000627:therapeutic use; D016014:Linear Models; D016015:Logistic Models; D008297:Male; D015999:Multivariate Analysis; D011092:Polyethylene Glycols / Q000627:therapeutic use; D011994:Recombinant Proteins / Q000627:therapeutic use; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D000418:Albumins; D000998:Antiviral Agents; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; C531108:albinterferon alfa-2b; C100416:peginterferon alfa-2a