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 <1 log(10) decline (n = 38), partial responders had >or=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. Copyright (c) 2010 AGA Institute. Published by Elsevier Inc. All rights reserved.
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 <1 log(10) decline (n = 38), partial responders had >or=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 tumornecrosis 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. Copyright (c) 2010 AGA Institute. Published by Elsevier Inc. All rights reserved.
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