title: Insulin resistance is a major determinant of sustained virological response in genotype 1 chronic hepatitis C patients receiving peginterferon alpha-2b plus ribavirin.
abstract: BACKGROUND
  Cross-sectional studies suggest insulin resistance is strongly associated with hepatic steatosis and fibrosis in patients with chronic hepatitis C (CHC), which might affect the efficacy of antiviral therapy. Aim To investigate retrospectively the impact of insulin resistance on treatment response in Chinese genotype 1 CHC patients receiving a 24-week course therapy with peginterferon alpha-2b/ribavirin.
  
  
  METHODS
  A total of 133 biopsy-proven CHC patients were enrolled for analyses. Insulin resistance was evaluated by homeostasis model assessment of insulin resistance (HOMA-IR). Hepatic fibrosis was graded by the METAVIR scoring system.
  
  
  RESULTS
  Mean HOMA-IR progressively elevated along with the severity of hepatic fibrosis (F1-F2 fibrosis: 2.55 +/- 0.16 vs. F3-F4 fibrosis: 3.61 +/- 0.20, P < 0.001). Compared with patients with sustained virological response (SVR), patients without SVR had significantly higher percentages of F3-F4 fibrosis (62.2% vs. 21.6%, P < 0.001) and baseline high viral load (>or=600,000 IU/mL; 64.4% vs. 35.6%, P = 0.038). In addition, patients without SVR had significantly higher plasma levels of insulin (15.03 +/- 0.89 vs. 10.19 +/- 0.55 microU/mL, P < 0.001) and HOMA-IR values (3.76 +/- 0.23 vs. 2.50 +/- 0.15, P < 0.001). Multivariate analyses showed that F1-F2 fibrosis (odds ratio: 4.49, P = 0.001), HOMA-IR < 2 (odds ratio: 7.15, P = 0.005) and pre-treatment hepatitis C virus RNA < 600,000 IU/mL (odds ratio: 3.26, P = 0.012) were the independent factors associated with SVR.
  
  
  CONCLUSIONS
  Insulin resistance is a major determinant of SVR in genotype 1 CHC patients receiving peginterferon alpha-2b/ribavirin. Strategies to modify insulin resistance may be effective in enhancing SVR before or during anti-viral therapy.
authors.affiliation: Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan. cjchu@vghtpe.gov.tw
authors.forename: C-J
authors.initials: CJ
authors.lastname: Chu
authors.forename: S-D
authors.initials: SD
authors.lastname: Lee
authors.forename: T-H
authors.initials: TH
authors.lastname: Hung
authors.forename: H-C
authors.initials: HC
authors.lastname: Lin
authors.forename: S-J
authors.initials: SJ
authors.lastname: Hwang
authors.forename: F-Y
authors.initials: FY
authors.lastname: Lee
authors.forename: R-H
authors.initials: RH
authors.lastname: Lu
authors.forename: M-I
authors.initials: MI
authors.lastname: Yu
authors.forename: C-Y
authors.initials: CY
authors.lastname: Chang
authors.forename: P-L
authors.initials: PL
authors.lastname: Yang
authors.forename: C-Y
authors.initials: CY
authors.lastname: Lee
authors.forename: F-Y
authors.initials: FY
authors.lastname: Chang
mesh_terms: D000998:Antiviral Agents / Q000627:therapeutic use*; D044466:Asian People; D003430:Cross-Sectional Studies; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics*; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D011994:Recombinant Proteins; D012189:Retrospective Studies; D012254:Ribavirin / Q000627:therapeutic use*; D013624:Taiwan; D016896:Treatment Outcome; D019562:Viral Load / Q000235:genetics
chemical_list: D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C417083:peginterferon alfa-2b