Viral Hepatitis

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Caspase activation is required for antiviral treatment response in chronic hepatitis C virus infection†

  1. Xandra Volkmann1,
  2. Markus Cornberg1,
  3. Heiner Wedemeyer1,
  4. Frank Lehner2,
  5. Michael P. Manns1,
  6. Klaus Schulze-Osthoff3,‡,*,
  7. Heike Bantel1

Article first published online: 25 MAY 2006

DOI: 10.1002/hep.21186

Issue

Hepatology

Hepatology

Volume 43, Issue 6, pages 1311–1316, June 2006

Additional Information

How to Cite

Volkmann, X., Cornberg, M., Wedemeyer, H., Lehner, F., Manns, M. P., Schulze-Osthoff, K. and Bantel, H. (2006), Caspase activation is required for antiviral treatment response in chronic hepatitis C virus infection. Hepatology, 43: 1311–1316. doi: 10.1002/hep.21186

Author Information

  1. 1

    Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany

  2. 2

    Department of Visceral and Transplantation Surgery, Hannover Medical School, Hannover, Germany

  3. 3

    Institute of Molecular Medicine, University of Düsseldorf, Düsseldorf, Germany

  1. ‡

    fax (49) 511-5326998

*Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625 Hannover, Germany

  1. †

    Potential conflict of interest: Nothing to report.

  2. ‡

    fax (49) 511-5326998

Publication History

  1. Issue published online: 25 MAY 2006
  2. Article first published online: 25 MAY 2006
  3. Manuscript Accepted: 5 MAR 2006
  4. Manuscript Received: 8 DEC 2005

Funded by

  • Deutsche Forschungsgemeinschaft. Grant Number: SFB 575
  • German competence network on hepatitis (HepNet)

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Abstract

Only half of patients with chronic hepatitis C virus (HCV) infection and genotype-1 show a sustained antiviral response to the current antiviral therapy. The reason this treatment fails is unclear, and no reliable marker exists that predicts the treatment outcome. In the present study, we investigated the apoptotic activation of caspases in HCV patients undergoing antiviral therapy with regard to the treatment outcome. We determined caspase activation in sera from patients who were either responding or nonresponding to antiviral therapy by using two novel caspase assays, an immunological and a luminometric enzyme test. We found that compared with nonresponding individuals, responding patients showed significantly (P < .05) increased caspase activity, which was closely correlated with virus elimination (r = 0.81). The cutoff value of serum caspase activity was determined, which correctly predicted the treatment outcome with a sensitivity of 70% and a specificity of 82% (area under the curve 0.845; 95% CI). In conclusion, hepatic caspase activity might play a role in HCV clearance and could also predict the efficacy of antiviral therapy. (HEPATOLOGY 2006;43: 1311–1316.)

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