Insulin resistance is a major determinant of sustained virological response in genotype 1 chronic hepatitis C patients receiving peginterferon a-2b plus ribavirin C.-J. CHU*,  , S.-D. LEE*,  , T.-H. HUNG*,  , H.-C. LIN*,  , S.-J. HWANG*, à ,  , F.-Y. LEE*,§,  , R.-H. LU*, M.-I. YU*, C.-Y. CHANG*, P.-L. YANG*, C.-Y. LEE* & F.-Y. CHANG*,   *Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan;  National Yang-Ming University School of Medicine, Taipei, Taiwan; àDepartment of Family Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; §Division of General Medicine, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, Republic of China Correspondence to: Dr C.-J. Chu, Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, No-201, Sec. 2, Shih-Pai Road, Taipei, Taiwan 11217, Republic of China. E-mail: cjchu@vghtpe.gov.tw Publication data Submitted 14 December 2007 First decision 7 January 2008 Resubmitted 7 July 2008 Accepted 28 July 2008 Epub Accepted Article 1 August 2008 SUMMARY 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 treat- ment response in Chinese genotype 1 CHC patients receiving a 24-week course therapy with peginterferon a-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 META- VIR 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 (‡600 000 IU ⁄ mL; 64.4% vs. 35.6%, P = 0.038). In addition, patients with- out SVR had significantly higher plasma levels of insulin (15.03  0.89 vs. 10.19  0.55 lU ⁄ 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 a-2b ⁄ ribavirin. Strategies to modify insulin resistance may be effective in enhancing SVR before or during anti-viral therapy. Aliment Pharmacol Ther 29, 46–54 Alimentary Pharmacology & Therapeutics 46 ª 2008 The Authors Journal compilation ª 2008 Blackwell Publishing Ltd doi:10.1111/j.1365-2036.2008.03823.x