Virological breakthrough and resistance in patients with chronic hepatitis B receiving nucleos(t)ide analogues in clinical practice

Authors

  • Chanunta Hongthanakorn,

    1. Division of Gastroenterology, Department of Internal Medicine, University of Michigan Health System, Ann Arbor, MI
    Search for more papers by this author
  • Watcharasak Chotiyaputta,

    1. Division of Gastroenterology, Department of Internal Medicine, University of Michigan Health System, Ann Arbor, MI
    Search for more papers by this author
  • Kelly Oberhelman,

    1. Division of Gastroenterology, Department of Internal Medicine, University of Michigan Health System, Ann Arbor, MI
    Search for more papers by this author
  • Robert J. Fontana,

    1. Division of Gastroenterology, Department of Internal Medicine, University of Michigan Health System, Ann Arbor, MI
    Search for more papers by this author
  • Jorge A. Marrero,

    1. Division of Gastroenterology, Department of Internal Medicine, University of Michigan Health System, Ann Arbor, MI
    Search for more papers by this author
  • Tracy Licari,

    1. Division of Gastroenterology, Department of Internal Medicine, University of Michigan Health System, Ann Arbor, MI
    Search for more papers by this author
  • Anna S. F. Lok

    Corresponding author
    1. Division of Gastroenterology, Department of Internal Medicine, University of Michigan Health System, Ann Arbor, MI
    • Division of Gastroenterology, University of Michigan Health System, 3912 Taubman Center, SPC 5362, 1500 East Medical Center Drive, Ann Arbor, MI 48109
    Search for more papers by this author
    • fax: 734-936-7392


  • Potential conflict of interest: R.J.F. did consulting/research for Bristol-Myers Squibb and GlaxoSmithKline, and was on the Speaker's Bureau for Gilead Sciences and Genentech. A.S.F.L. did consulting for Gilead Sciences, Roche, Bristol-Myers Squibb, and GlaxoSmithKline; and received grant/research support from Bristol-Myers Squibb, Gilead Sciences, GlaxoSmithKline, Schering-Plough, and Roche.

Abstract

Virological breakthrough (VBT) is the first manifestation of antiviral drug resistance during nucleos(t)ide analogue (NUC) treatment of chronic hepatitis B (CHB), but not all VBTs are due to drug resistance. This study sought to determine the incidence of VBT and genotypic resistance (GR) in patients with CHB who were receiving NUCs in clinical practice. Records of patients with CHB who were receiving NUCs were reviewed. All patients with VBT were tested for drug resistance mutations. Of 148 patients included, 73% were men and mean age was 44.9 years. During a mean follow-up of 37.5 ± 20.1 months, 39 (26%) patients had at least 1 VBT. Of these 39 patients, 15 (38%) were not confirmed to have VBT on retesting, and 10 of these 15 had no evidence of GR. The cumulative probability of VBT, confirmed VBT, and GR at 5 years was 46.1%, 29.7%, and 33.9%, respectively. In multivariate analysis, failure to achieve undetectable hepatitis B virus (HBV) DNA was the only factor significantly associated with VBT. Among the 10 patients who had VBT but no confirmed VBT or GR and who were maintained on the same medications, serum HBV DNA decreased in all 10, and nine had undetectable HBV DNA at a mean of 6.8 months after the VBT. Four patients had persistently undetectable HBV DNA, six had transient increase in HBV DNA during follow-up, and none had GR. Conclusion: VBT was common in patients with CHB receiving NUCs in clinical practice, but nearly 40% of the VBTs were not related to antiviral drug resistance. Counseling of patients with CHB on medication adherence and confirmation of VBT and/or GR can avoid unnecessary changes in antiviral medications. (HEPATOLOGY 2011;)

Ancillary