HCV is independently associated with increased IR after OLT. These findings provide a possible pathogenetic basis for the association of DM with HCV.

Bacground & Aims Hepatitis C virus (HCV) infection is associated with an increased prevalence of diabetes and insulin resistance (IR); whether this is a causal relationship has not been established. Methods We performed a longitudinal study within the lead-in phase of the Hepatitis C Antiviral Long-Term Treatment against Cirrhosis (HALT-C) Trial to evaluate whether suppression of hepatitis C is associated with improvement in IR. Participants had advanced hepatic fibrosis and carried non-3 HCV genotypes (n=96). Patients underwent 24 weeks of pegylated interferon (PEG IFN) and ribavirin therapy and were categorized into HCV clearance groups at week 20 based on HCV RNA levels: null responders (NR) had < 1 log10 decline (n=38); partial responders (PR) had ≥1 log10 decline (n=37), but detectable HCV RNA, and complete responders (CR) had no detectable HCV RNA (n=21). The primary outcomewas change (week 20 minus week 0) in IR using the homeostasis model assessment (HOMA2-IR). Results Adjusting only for baseline HOMA2-IR, mean HOMA2-IR differences were −2.23 (CR), −0.90 (PR), and +0.18 (NR) (p =0.036). The observed differences in mean HOMA2-IR scores were ordered in a linear fashion across response groups (p=0.01). The association between HCV clearance and improvement in HOMA2-IR could not be accounted for by adiponectin or tumor necrosis alfa, and was independent of potential confounders including age, gender, ethnicity, BMI, duration of infection, medications used, and fibrosis. Conclusion HCV suppression correlates with improvement in insulin resistance. These data provide further support for a role of HCV in the development of insulin resistance.

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