Sustained Virological Response reduces insulin resistance in patients with genotype 1 Chronic Hepatitis C

Background and Aims: Chronic hepatitis C (CHC) has been associated with an increased prevalence of diabetes and insulin resistance (IR). Recently, a genotype-specific association between HCV genotype 1 and IR has been proposed. However it remains unclear whether this is a causal relationship. The present study investigated the association of sustained virologic response (SVR) with IR in patients with genotype 1 Chronic Hepatitis C. Methods: Thirty-five treatment-naïve non diabetic patients with genotype 1 CHC were enrolled and all were receiving combination therapy with peginterferon alfa-2a plus ribavirin for 48 weeks. IR was measured at wk 0, 12, 24, or 48, and post-treatment wk12 using the homeostasis model for assessment of IR (HOMA-IR). Clinical evaluation by a single pathologist included age, gender, race, BMI, HCV viral load, alanine aminotransferase, gamma-glutamyl transpeptidase, total cholesterol, HDL, LDL- cholesterol, triglycerides, and baseline liver biopsy for steatosis, METAVIR inflammatory grade, and fibrosis stage. IR was considered categorically, setting a threshold of HOMA-IR >3. Change in HOMA-IR post-therapy was considered as a continuous variable; HOMA-IR data were log-transformed for analysis as a continuous variable. Results: Matched pre- and 12wk post HOMA-IR measurements were available from 35 nondiabetic patients with genotype 1 CHC. SVR rates were 60% in genotype 1 CHC patients. SVR was associated with a reduction in prevalence of IR (P < 0.001). This was independent of changes in BMI, alanine aminotransferase, gamma-glutamyl transpeptidase, and lipid levels. HOMA-IR did not change in nonresponders. Conclusions: SVR was associated with a reduction in HOMA-IR in patients with genotype 1 CHC. The results suggest that HCV genotype 1 can play a causal role in the development of IR, which may be reversed by viral eradication.