Prediction of sustained response to peginterferon alfa-2b for hepatitis B e antigen–positive chronic hepatitis B using on-treatment hepatitis B surface antigen decline

Authors

  • Milan J. Sonneveld,

    1. Gastroenterology and Hepatology, Erasmus MC University Medical Center, Rotterdam, The Netherlands
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  • Vincent Rijckborst,

    1. Gastroenterology and Hepatology, Erasmus MC University Medical Center, Rotterdam, The Netherlands
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  • Charles A. B. Boucher,

    1. Virology, Erasmus MC University Medical Center, Rotterdam, TheNetherlands
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  • Bettina E. Hansen,

    1. Gastroenterology and Hepatology, Erasmus MC University Medical Center, Rotterdam, The Netherlands
    2. Biostatistics, Erasmus MC University Medical Center, Rotterdam, TheNetherlands
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  • Harry L. A. Janssen

    Corresponding author
    1. Gastroenterology and Hepatology, Erasmus MC University Medical Center, Rotterdam, The Netherlands
    • Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center Rotterdam, ’s Gravendijkwal 230, room Ha 204, 3015 CE Rotterdam, The Netherlands
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    • fax: +31 (0) 10 436 5916


  • Dr. Janssen is a consultant for, and received grants from Roche, Bristol-Myers Squibb, Novartis, Gilead, and Schering-Plough.

Abstract

Serum hepatitis B surface antigen (HBsAg) levels may reflect the immunomodulatory efficacy of pegylated interferon (PEG-IFN). We investigated within a large randomized trial whether quantitative HBsAg levels predict response to PEG-IFN in patients with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B. Serum HBsAg was measured in samples taken at baseline and weeks 4, 8, 12, 24, 52, and 78 of 221 patients treated with PEG-IFN alfa-2b with or without lamivudine for 52 weeks. HBsAg decline was compared between treatment arms and between responders and nonresponders. Response was defined as HBeAg loss with HBV DNA < 10,000 copies/mL at 26 weeks after treatment (week 78); 43 of 221 (19%) patients achieved a response. One year of PEG-IFN with or without lamivudine resulted in a significant decline in serum HBsAg, which was sustained after treatment (decline 0.9 log IU/mL at week 78, P < 0.001). Patients treated with combination therapy experienced a more pronounced on-treatment decline, but relapsed subsequently. Responders experienced a significantly more pronounced decline in serum HBsAg compared to nonresponders (decline at week 52: 3.3 versus 0.7 log IU/mL, P < 0.001). Patients who achieved no decline at week 12 had a 97% probability of nonresponse through posttreatment follow-up and no chance of HBsAg loss. In a representative subset of 149 patients similar results were found for prediction through long-term (mean 3.0 years) follow-up. Conclusion: PEG-IFN induces a significant decline in serum HBsAg in HBeAg-positive patients. Patients who experience no decline from baseline at week 12 have little chance of achieving a sustained response and no chance of HBsAg loss and should be advised to discontinue therapy with PEG-IFN. (HEPATOLOGY 2010)

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