Adefovir rapidly suppresses hepatitis B in HBeAg-negative patients developing genotypic resistance to lamivudine

Authors

  • Pietro Lampertico,

    1. Department of Gastroenterology and Endocrinology, A. M. and A. Migliavacca Center for Liver Disease, IRCCS Maggiore Hospital, Fondazione Policlinico, Mangiagalli e Regina Elena, University of Milan, Milan, Italy
    Search for more papers by this author
  • Mauro Viganò,

    1. Department of Gastroenterology and Endocrinology, A. M. and A. Migliavacca Center for Liver Disease, IRCCS Maggiore Hospital, Fondazione Policlinico, Mangiagalli e Regina Elena, University of Milan, Milan, Italy
    Search for more papers by this author
  • Elena Manenti,

    1. Department of Gastroenterology and Endocrinology, A. M. and A. Migliavacca Center for Liver Disease, IRCCS Maggiore Hospital, Fondazione Policlinico, Mangiagalli e Regina Elena, University of Milan, Milan, Italy
    Search for more papers by this author
  • Massimo Iavarone,

    1. Department of Gastroenterology and Endocrinology, A. M. and A. Migliavacca Center for Liver Disease, IRCCS Maggiore Hospital, Fondazione Policlinico, Mangiagalli e Regina Elena, University of Milan, Milan, Italy
    Search for more papers by this author
  • Giovanna Lunghi,

    1. Division of Hygiene, IRCCS Maggiore Hospital, Fondazione Policlinico, Mangiagalli e Regina Elena, University of Milan, Milan, Italy
    Search for more papers by this author
  • Massimo Colombo

    Corresponding author
    1. Department of Gastroenterology and Endocrinology, A. M. and A. Migliavacca Center for Liver Disease, IRCCS Maggiore Hospital, Fondazione Policlinico, Mangiagalli e Regina Elena, University of Milan, Milan, Italy
    • Department of Gastroenterology and Endocrinology, IRCCS Maggiore Hospital, University of Milan, Via F. Sforza 35-20122, Milan, Italy
    Search for more papers by this author
    • fax: (39) 0250320410


  • Potential conflict of interest: Nothing to report.

Abstract

Progression of hepatitis B in patients with lamivudine-resistant strains is slowed down by adefovir dipivoxil (ADV). Whether the time point of ADV administration (genotypic vs. phenotypic resistance) influences the outcome of therapy is unknown. We compared the outcome of ADV therapy in hepatitis B e antigen (HBeAg)-negative chronic hepatitis B patients with genotypic and phenotypic resistance to lamivudine. Ten milligrams of ADV was administered daily for 2 years to 46 HBeAg-negative patients at the time of phenotypic resistance (group A, >6 log10 copies/mL of hepatitis B virus [HBV] DNA and high alanine aminotransferase [ALT] levels) and 28 patients at the time of genotypic resistance (group B, 3-6 log10 copies/mL of HBV-DNA and normal ALT). HBV DNA was assessed every 2 months using Versant 3.0 assay, and lamivudine resistance was confirmed via INNO-LiPA assay in all patients. By month 3, HBV DNA tested negative in all patients from group B compared with only 20 (46%) in group A (P < .0001). The 2-year rates of virological response were 100% in the former patients and 78% in the latter ones (P < .0001). ALT levels remained persistently normal in all group B patients, whereas in group A patients they normalized at rates of 50% at month 6 (P < .0001), 72% at month 12 (P < .01), and 93% at month 24. None of the patients developed ADV resistance or ADV-related side effects. In conclusion, to optimize antiviral treatment in HBeAg-negative patients selecting resistant strains to lamivudine, ADV should be added to lamivudine as soon as genotypic resistance is detected. (HEPATOLOGY 2005.)

Ancillary