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Hepatology
Original article
Viral clearance is associated with improved insulin resistance in genotype 1 chronic hepatitis C but not genotype 2/3
  1. Alexander J Thompson1,
  2. Keyur Patel1,
  3. Wan-Long Chuang2,
  4. Eric J Lawitz3,
  5. Maribel Rodriguez-Torres4,
  6. Vinod K Rustgi5,
  7. Robert Flisiak6,
  8. Stephen Pianko7,
  9. Moises Diago8,
  10. Sanjeev Arora9,
  11. Graham R Foster10,
  12. Michael Torbenson11,
  13. Yves Benhamou12,
  14. David R Nelson13,
  15. Mark S Sulkowski11,
  16. Stefan Zeuzem14,
  17. Erik Pulkstenis15,
  18. G Mani Subramanian15,
  19. John G McHutchison1,
  20. for the ACHIEVE-1 and ACHIEVE-2/3 Study Teams*
  1. 1Duke Clinical Research Institute, Duke University Medical Center, Durham, North Carolina, USA
  2. 2Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
  3. 3Alamo Medical Research, San Antonio, Texas, USA
  4. 4Fundación de Investigación de Diego, Santurce, Puerto Rico, USA
  5. 5Metropolitan Research, Fairfax, Virginia, USA
  6. 6Medical University of Bialystok, Bialystok, Poland
  7. 7Monash Medical Centre, Clayton, Victoria, Australia
  8. 8Hospital Quiron de Valencia, Barcelona, Spain
  9. 9University of New Mexico, Albuquerque, USA
  10. 10Queen Mary University of London, and Barts and The London NHS Trust, London, UK
  11. 11Johns Hopkins Center for Viral Hepatitis, Baltimore, Maryland, USA
  12. 12Hôpital Pitié-Salpêtrière, Paris, France
  13. 13University of Florida, Gainesville, Florida, USA
  14. 14J W Goethe University Hospital, Frankfurt, Germany
  15. 15Human Genome Sciences Inc, Rockville, Maryland, USA
  1. Correspondence to Alexander J Thompson, Duke Clinical Research Institute, Duke University Medical Center, P O Box 17969, Durham, NC 27715, USA; alexander.thompson{at}svhm.org.au

Abstract

Objectives Genotype-specific associations between hepatitis C virus (HCV) and insulin resistance (IR) have been described, but a causal relationship remains unclear. This study investigated the association between a sustained virological response (SVR) and IR after chronic HCV therapy.

Methods 2255 treatment-naive patients with chronic HCV genotype 1 or 2/3 were enrolled in two phase 3 trials of albinterferon alpha-2b versus pegylated interferon alpha-2a for 48 or 24 weeks, respectively. IR was measured before treatment and 12 weeks after treatment using homeostasis model assessment (HOMA)-IR.

Results Paired HOMA-IR measurements were available in 1038 non-diabetic patients (497 with genotype 1; 541 with genotype 2/3). At baseline the prevalence of HOMA-IR >3 was greater in patients with genotype 1 than 2/3 (33% vs 27%; p=0.048). There was a significant reduction in the prevalence of IR in patients with genotype 1 achieving SVR (δ 10%; p<0.001), but not in genotype 1 non-responders or those with genotype 2/3. Multivariate analysis indicated that SVR was associated with a significant reduction in mean HOMA-IR in patients with genotype 1 (p=0.004), but not in those with genotype 2/3, which was independent of body mass index, alanine transaminase, γ-glutamyl transpeptidase and lipid level changes.

Conclusions SVR is associated with a reduction in HOMA-IR in patients with HCV genotype 1 but not in those with genotype 2/3. Genotype 1 may have a direct effect on the development of IR, independent of host metabolic factors, and may be partially reversed by viral eradication.

  • ACHIEVE
  • albinterferon alpha-2b
  • hepatitis C virus
  • insulin resistance
  • sustained virologic response
  • diabetes mellitus
  • HCV
  • interferon

https://doi.org/10.1136/gut.2010.236158

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    Footnotes

    • ↵* A complete list of the ACHIEVE-1 and -2/3 investigators appears in online appendix 1

    • Funding This study was supported by Human Genome Sciences Inc, Rockville, Maryland, USA and Novartis Pharma AG, Basel, Switzerland. Geoff Marx of BioScience Communications, New York, New York, provided editorial assistance supported by HGS and Novartis. The parent study from which data were collected for this analysis was funded by Human Genome Sciences Inc and Novartis.

    • Competing interests AJT received funding support from the Duke Clinical Research Institute, the National Health and Medical Research Council of Australia and the Gastroenterology Society of Australia. EJL has received research grants from Human Genome Sciences (HGS), Hoffman-LaRoche Inc, Nutley, New Jersey, and Novartis. MR-T has received research grants from Novartis and Roche and is a consultant to Roche. VKR is a consultant for HGS and Novartis. RF is a consultant for HGS. SP is a consultant for, advises and is on the speakers' bureau of HGS, Novartis and Roche. SA has received research support from and is a consultant to HGS. GRF has received funding from Novartis and Roche. YB has received grant support from and has contributed to clinical trials, is a member of speakers' bureaus and has consulted for HGS, Novartis and Roche. DRN has received research support from and is a consultant to HGS. MSS is a consultant for HGS and Novartis. SZ has received consulting fees from HGS, Novartis and Roche and lecture fees from Novartis and Roche. EP and GMS are employees of and own stock in HGS. JGMcH has received research grants from and is a consultant to HGS, Novartis and Roche. No other potential conflicts of interest relevant to this article were reported.

    • Ethics approval This study was approved by the institutional review board of each participating site (represented by each of the authors contained in appendix 1) and informed consent was obtained from each patient.

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