Adefovir-resistant hepatitis B can be associated with viral rebound and hepatic decompensation

Scott K. Fung, Pietro Andreone, Steve H. Han, K. Rajender Reddy, Arie Regev, Emmet B. Keeffe, Munira Hussain, Carmela Cursaro, Pamela Richtmyer, Jorge A. Marrero, Anna S F Lok

Research output: Contribution to journalArticle

176 Scopus citations

Abstract

Background/Aims: The susceptibility of adefovir-resistant hepatitis B virus (HBV) mutants is only reduced by 3-10-fold in in vitro studies, suggesting that virologic breakthrough and clinical deterioration are unlikely. The aim of this study was to describe the clinical course of patients with adefovir-resistant HBV infection. Methods: Testing for adefovir-resistant mutations was performed on patients who had a suboptimal response or virologic breakthrough on adefovir. Adefovir-resistant mutations were detected using a line probe assay and direct sequencing of the HBV P-gene. Results: Eight male patients with pre-existing lamivudine resistance or breakthrough (mean age 47±13 years) were found to have adefovir-resistant mutations rtA181V/T or rtN236T. Baseline median ALT was 66 IU/L (range, 27-1161) and median HBV DNA 7.9 log10 copies/ml (range, 6-8.3). At the time of adefovir resistance (mean of 20±9 months), HBV DNA increased to ≥5 log10 copies/ml in 7 patients. After detection of adefovir resistance, hepatic decompensation occurred in 2 patients, 1 of whom died. Salvage therapy with lamivudine, entecavir or tenofovir was given to 7 patients and a reduction in HBV DNA by ≥3 log10 was seen in 3 patients. Conclusions: In conclusion, adefovir resistance can be associated with significant viral rebound and hepatic decompensation which may be fatal.

Original languageEnglish (US)
Pages (from-to)937-943
Number of pages7
JournalJournal of Hepatology
Volume43
Issue number6
DOIs
StatePublished - Dec 1 2005

Keywords

  • Adefovir
  • Entecavir
  • Hepatitis B
  • Lamivudine
  • Liver transplantation

ASJC Scopus subject areas

  • Hepatology

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    Fung, S. K., Andreone, P., Han, S. H., Rajender Reddy, K., Regev, A., Keeffe, E. B., Hussain, M., Cursaro, C., Richtmyer, P., Marrero, J. A., & Lok, A. S. F. (2005). Adefovir-resistant hepatitis B can be associated with viral rebound and hepatic decompensation. Journal of Hepatology, 43(6), 937-943. https://doi.org/10.1016/j.jhep.2005.05.037