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

Authors

  • Karsten Wursthorn,

    1. Department of Medicine, University Hospital Hamburg–Eppendorf, Hamburg, Germany
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    • K. Wursthorn and M. Lutgehetmann contributed equally to this work.

  • Marc Lutgehetmann,

    1. Department of Medicine, University Hospital Hamburg–Eppendorf, Hamburg, Germany
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    • K. Wursthorn and M. Lutgehetmann contributed equally to this work.

  • Maura Dandri,

    1. Department of Medicine, University Hospital Hamburg–Eppendorf, Hamburg, Germany
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  • Tassilo Volz,

    1. Department of Medicine, University Hospital Hamburg–Eppendorf, Hamburg, Germany
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  • Peter Buggisch,

    1. Department of Medicine, University Hospital Hamburg–Eppendorf, Hamburg, Germany
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    • 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.

  • Bernhard Zollner,

    1. Department of Microbiology, University Hospital Hamburg–Eppendorf, Hamburg, Germany
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    • 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.

  • Thomas Longerich,

    1. Institute of Pathology, University of Heidelberg, Heidelberg, Germany
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  • Peter Schirmacher,

    1. Institute of Pathology, University of Heidelberg, Heidelberg, Germany
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  • Frauke Metzler,

    1. Department of Medicine, University Hospital Hamburg–Eppendorf, Hamburg, Germany
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  • Myrga Zankel,

    1. Essex Pharma GmbH, Munich, Germany
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  • Conrad Fischer,

    1. Gilead Sciences Inc, Foster City, CA
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  • Graeme Currie,

    1. Gilead Sciences Inc, Foster City, CA
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  • Carol Brosgart,

    1. Gilead Sciences Inc, Foster City, CA
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  • Joerg Petersen

    Corresponding author
    1. Department of Medicine, University Hospital Hamburg–Eppendorf, Hamburg, Germany
    • Medizinische Klinik und Poliklinik I, Zentrum für Innere Medizin, Universitätsklinikum Hamburg—Eppendorf, Martinistr. 52, D-20246 Hamburg, Germany
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    • 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.

    • fax: (49) 40-42803-8065


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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