Reduction of Insulin Resistance With Effective Clearance of Hepatitis C Infection: Results From the HALT-C Trial

Background & 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 and ribavirin therapy and were categorized into HCV clearance groups at week 20 on the basis of HCV RNA levels; null responders had 10 decline (n = 38), partial responders had ≥1 log 10 decline (n = 37) but detectable HCV RNA, and complete responders had no detectable HCV RNA (n = 21). The primary outcome was change (week 20 minus week 0) in IR by using the homeostasis model assessment (HOMA2-IR). Results Adjusting only for baseline HOMA2-IR, mean HOMA2-IR differences were −2.23 (complete responders), −0.90 (partial responders), and +0.18 (null responders) ( P = .036). The observed differences in mean HOMA2-IR scores were ordered in a linear fashion across response groups ( P = .01). The association between HCV clearance and improvement in HOMA2-IR could not be accounted for by adiponectin or tumor necrosis factor–alpha and was independent of potential confounders including age, gender, ethnicity, body mass index, duration of infection, medications used, and fibrosis. Conclusions HCV suppression correlates with improvement in IR. These data provide further support for a role of HCV in the development of insulin resistance.