Viral Hepatitis

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Peginterferon alpha-2b plus adefovir induce strong cccDNA decline and HBsAg reduction in patients with chronic hepatitis B†

  1. Karsten Wursthorn1,‡,
  2. Marc Lutgehetmann1,‡,
  3. Maura Dandri1,
  4. Tassilo Volz1,
  5. Peter Buggisch1,†,
  6. Bernhard Zollner2,†,
  7. Thomas Longerich3,
  8. Peter Schirmacher3,
  9. Frauke Metzler1,
  10. Myrga Zankel4,
  11. Conrad Fischer5,
  12. Graeme Currie5,
  13. Carol Brosgart5,
  14. Joerg Petersen1,§,†,*

Article first published online: 29 AUG 2006

DOI: 10.1002/hep.21282

Issue

Hepatology

Hepatology

Volume 44, Issue 3, pages 675–684, September 2006

Additional Information

How to Cite

Wursthorn, K., Lutgehetmann, M., Dandri, M., Volz, T., Buggisch, P., Zollner, B., Longerich, T., Schirmacher, P., Metzler, F., Zankel, M., Fischer, C., Currie, G., Brosgart, C. and Petersen, J. (2006), Peginterferon alpha-2b plus adefovir induce strong cccDNA decline and HBsAg reduction in patients with chronic hepatitis B. Hepatology, 44: 675–684. doi: 10.1002/hep.21282

Author Information

  1. 1

    Department of Medicine, University Hospital Hamburg–Eppendorf, Hamburg, Germany

  2. 2

    Department of Microbiology, University Hospital Hamburg–Eppendorf, Hamburg, Germany

  3. 3

    Institute of Pathology, University of Heidelberg, Heidelberg, Germany

  4. 4

    Essex Pharma GmbH, Munich, Germany

  5. 5

    Gilead Sciences Inc, Foster City, CA

  1. †

    Potential conflict of interest: Dr. Zollner received travel grants from Gilead. Dr. Petersen received grants from Gilead. Dr. Buggisch is on the Speakers' Bureau for and received grants from Schering-Plough. He also received grants from Gilead.

  2. ‡

    K. Wursthorn and M. Lutgehetmann contributed equally to this work.

  3. §

    fax: (49) 40-42803-8065

*Medizinische Klinik und Poliklinik I, Zentrum für Innere Medizin, Universitätsklinikum Hamburg—Eppendorf, Martinistr. 52, D-20246 Hamburg, Germany

  1. †

    Potential conflict of interest: Dr. Zollner received travel grants from Gilead. Dr. Petersen received grants from Gilead. Dr. Buggisch is on the Speakers' Bureau for and received grants from Schering-Plough. He also received grants from Gilead.

Publication History

  1. Issue published online: 29 AUG 2006
  2. Article first published online: 29 AUG 2006
  3. Manuscript Accepted: 25 MAY 2006
  4. Manuscript Received: 11 MAR 2006

Funded by

  • Deutsche Forschungsgemeinschaft. Grant Number: Pe/608 2-4
  • Virgil (European Union Network of Excellence)

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Abstract

Hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) is responsible for persistent infection of hepatocytes. The aim of this study was to determine changes in intrahepatic cccDNA in patients with chronic hepatitis B (CH-B) during 48 weeks of antiviral therapy and its correlation to virological, biochemical, and histological parameters. Twenty-six HBsAg-positive CH-B patients received combination treatment with pegylated interferon alpha-2b (peg-IFN) and adefovir dipivoxil (ADV) for 48 weeks. Paired liver biopsies from before and at the end of treatment were analyzed for intrahepatic HBV-DNA. Median serum HBV-DNA had decreased by −4.9 log10 copies/mL at the end of treatment and was undetectable in 13 individuals (54%). Median intrahepatic total HBV-DNA and cccDNA had decreased by −2.2 and −2.4 log10, respectively. Changes in intracellular HBV-DNA positively correlated with HBsAg serum reduction and were accompanied by a high number of serological responders. Eight of 15 HBeAg-positive patients lost HBeAg, and five developed anti-HBe antibodies during treatment. These eight patients exhibited lower cccDNA levels before and at the end of therapy than did patients without HBeAg loss. Four patients developed anti-HBs antibodies. ALT normalized in 11 patients. The number of HBs-antigen- and HBc-antigen-positive hepatocytes was significantly lower after treatment, suggesting the involvement of cytolytic mechanisms. In conclusion, combination therapy with peg-IFN and ADV led to marked decreases in serum HBV-DNA and intrahepatic cccDNA, which was significantly correlated with reduced HBsAg. (HEPATOLOGY 2006;44:675–684.)

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