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Danoprevir, an HCV NS3/4A protease inhibitor, improves insulin sensitivity in patients with genotype 1 chronic hepatitis C
  1. Rami Moucari1,
  2. Nicole Forestier2,
  3. Dominique Larrey3,
  4. Dominique Guyader4,
  5. Patrice Couzigou5,
  6. Yves Benhamou6,
  7. Hélène Voitot7,
  8. Michel Vidaud7,
  9. Scott Seiwert8,
  10. Bill Bradford8,
  11. Stefan Zeuzem2,
  12. Patrick Marcellin1
  1. 1Service d'Hépatologie et INSERM U773-CRB3, Hôpital Beaujon, Clichy, France
  2. 2J. W. Goethe-University Hospital, Frankfurt, Germany
  3. 3Service d'Hépato-Gastro-Entérologie et de Transplantation Hépatique, CHU de Montpellier, France
  4. 4Service des Maladies du Foie, CHU de Rennes, France
  5. 5Service d'Hépato-Gastro-Entérologie, CHU de Bordeaux, France
  6. 6Service d'Hépato-Gastro-Entérologie, Hôpital Pitié Salpêtrière, Paris, France
  7. 7Service de Biochimie, Hôpital Beaujon, Clichy, France
  8. 8InterMune, Brisbane, California, USA
  1. Correspondence to Rami Moucari, Service d'Hépatologie et INSERM U773-CRB3, Hôpital Beaujon, Clichy, France; rmoucari{at}yahoo.com

Abstract

Background/aim Insulin resistance (IR) is a major predictor of treatment failure in patients with hepatitis C virus (HCV) infection treated with peginterferon/ribavirin. The aim of this study was to evaluate the short-term effect of an HCV protease inhibitor monotherapy on IR in parallel with an antiviral effect.

Patients/methods In a phase 1b placebo-controlled study, four cohorts of treatment-naïve patients with genotype 1 HCV received danoprevir (ITMN-191/RG7227), a protease inhibitor, or placebo (8/2 patients in each cohort respectively) in a gelatin capsule every 12 h (100, 200 mg) or 8 h (100, 200 mg) for 14 days. A fifth cohort including prior non-responders to peginterferon/ribavirin was similarly randomised to receive placebo or 300 mg danoprevir every 12 h. IR was assessed with the homeostasis model (HOMA-IR) at baseline and days 7, 14 and 15.

Results Serum HCV-RNA and HOMA-IR correlated significantly (Spearman rho=0.379, p<0.0001). At baseline, mean±SD serum HCV-RNA level and mean±SD HOMA-IR score were 6.2±0.5 log10IU/ml and 3.8±1.9, respectively. At the end of 14 days of monotherapy the mean±SD decrease in viral load was 2.2±1.3 log10IU/ml (p<0.0001) in patients who received the active drug (n=40). In parallel, the mean±SD HOMA-IR score also decreased in these patients by 1.6±1.1 (p<0.0001), with a close correlation between the extent of HOMA-IR improvement and the decrease in viral load. By contrast, serum HCV-RNA and HOMA-IR remained unchanged in patients who received placebo (n=10; 6.3±0.5 log10IU/ml and 3.8±2.5, respectively).

Conclusion HCV protease inhibitor may restore insulin sensitivity in patients with genotype 1 HCV. The place of insulin sensitisers remains to be determined in the era of triple therapy.

  • HOMA-IR
  • insulin resistance
  • SVR
  • hepatitis C

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Footnotes

  • Linked articles 222703.

  • Funding This study was supported by a grant from InterMune Laboratory, Brisbane, California, USA.

  • Competing interests None.

  • Ethics approval This study was approved by ethical committees in France and Germany in 2006.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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