Insulin resistance is a major determinant of sustained virological response in genotype 1 chronic hepatitis C patients receiving peginterferon alpha-2b plus ribavirin.

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.