title: Chronic hepatitis C genotype 1 patients with insulin resistance treated with pioglitazone and peginterferon alpha-2a plus ribavirin.
abstract: Patients with chronic hepatitis C and insulin resistance are less likely to respond to anti-hepatitis C virus (HCV) therapy and are at risk for more rapid fibrosis progression. Coadministration of pioglitazone with peginterferon/ribavirin improves insulin sensitivity and increases virologic response rates in insulin-resistant HCV genotype 4 patients, but it is unclear whether this finding applies to genotype 1 patients. For this reason we randomized treatment-naive HCV genotype 1 patients with insulin resistance to receive either standard care (peginterferon alpha-2a plus ribavirin for 48 weeks, n = 73) or pioglitazone 30-45 mg/day plus standard care (n = 77) in an open-label multicenter trial. Patients randomized to pioglitazone received the drug during a 16-week run-in phase, the 48-week standard-care phase, and the 24-week untreated follow-up phase. Pioglitazone treatment improved hemoglobin A1c (HbA1c), plasma glucose, insulin levels, and homeostasis model assessment of insulin resistance score and increased serum adiponectin levels during the 16-week run-in phase and maintained these improvements during the standard-care phase. However, we observed no statistically significant difference between the two groups in the primary efficacy endpoint, the decrease from baseline to Week 12 of peginterferon alpha-2a/ribavirin treatment in mean log(10) HCV RNA titer (-3.5 ± 1.71 and -3.7 ± 1.62 IU/mL in the pioglitazone and standard-care groups, respectively, Δ = 0.21 IU/mL, P = 0.4394).
  
  
  CONCLUSIONS
  Treatment with pioglitazone before and during treatment with peginterferon alpha-2a plus ribavirin improved several indices of glycemic control in patients with chronic hepatitis C and insulin resistance, but did not improve virologic response rates compared with peginterferon alpha-2a plus ribavirin alone.
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Medicine, Brooke Army Medical Center, Fort Sam Houston, TX 78234, USA. STEPHEN.A.HARRISON@us.army.mil
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Harrison
authors.forename: Fayez M
authors.initials: FM
authors.lastname: Hamzeh
authors.forename: Jian
authors.initials: J
authors.lastname: Han
authors.forename: Prashant K
authors.initials: PK
authors.lastname: Pandya
authors.forename: Muhammed Y
authors.initials: MY
authors.lastname: Sheikh
authors.forename: John M
authors.initials: JM
authors.lastname: Vierling
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage / Q000009:adverse effects; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000453:epidemiology; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D016174:Hepacivirus / Q000187:drug effects* / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000453:epidemiology / Q000821:virology; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000009:adverse effects; D007333:Insulin Resistance / Q000502:physiology*; D016898:Interferon-alpha / Q000008:administration & dosage* / Q000009:adverse effects; D008103:Liver Cirrhosis / Q000453:epidemiology / Q000821:virology; D008297:Male; D008875:Middle Aged; D000077205:Pioglitazone; D011092:Polyethylene Glycols / Q000008:administration & dosage* / Q000009:adverse effects; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects; D012254:Ribavirin / Q000008:administration & dosage* / Q000009:adverse effects; D012307:Risk Factors; D045162:Thiazolidinediones / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D007004:Hypoglycemic Agents; D016898:Interferon-alpha; D011994:Recombinant Proteins; D045162:Thiazolidinediones; D011092:Polyethylene Glycols; D012254:Ribavirin; C100416:peginterferon alfa-2a; D000077205:Pioglitazone