Kinetics of hepatitis B surface antigen loss in patients with HBeAg-positive chronic hepatitis B treated with tenofovir disoproxil fumarate

Patrick Marcellin, Maria Buti, Zahari Krastev, Robert A. De Man, Stefan Zeuzem, Lillian Lou, Anuj Gaggar, John F. Flaherty, Benedetta Massetto, Lanjia Lin, Phillip Dinh, G. Mani Subramanian, John G. McHutchison, Robert Flisiak, Selim Gurel, Geoffrey M. Dusheiko, E. Jenny Heathcote

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Abstract

Background & Aims In a study of 266 chronic hepatitis B e antigen (HBeAg)-positive patients, 23 experienced hepatitis B surface antigen (HBsAg) loss with up to 5 years of tenofovir disoproxil fumarate (TDF) treatment. HBsAg kinetics in patients with and without HBsAg loss and predictors of HBsAg loss were evaluated. Methods HBsAg levels were quantified every 12 weeks. A multivariable regression analysis, involving prespecified baseline characteristics and on-treatment response parameters, was performed; a stepwise procedure identified independent predictors of HBsAg loss. Results Among patients with HBsAg loss, 14 (61%), 1 (4%), 0 and 7 (30%) were genotypes A through D, respectively; 1 (4%) was genotype F. HBsAg loss was preceded by viral suppression (HBV DNA <29 IU/ml; n = 23) and HBeAg loss (n = 19). Among treated patients the strongest independent predictors of HBsAg loss were Caucasian race with genotype A/D and ≤4 years of infection (HR = 14.3, 95% confidence interval [CI] 4.7-43.4; p <0.0001) and an HBsAg decline of ≥1 log10 IU/ml at week 24 (HR = 13.7, 95% CI 5.6-33.7; p <0.0001). Among TDF-treated patients, a reduction in HBsAg level of ≥1-log10 by week 12 or 24 had a positive predictive value of 35%-45%, respectively, and a negative predictive value of 94%-97%, respectively. Conclusions HBsAg loss in HBeAg-positive patients receiving TDF involves a chronology of virologic and serologic responses; patients with HBV genotypes A or D and a rapid early decline in HBsAg are more likely to lose HBsAg.

Original languageEnglish (US)
Pages (from-to)1228-1237
Number of pages10
JournalJournal of Hepatology
Volume61
Issue number6
DOIs
StatePublished - Dec 1 2014

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Keywords

  • Chronic hepatitis B
  • Hepatitis B surface antigen
  • Tenofovir disoproxil fumarate

ASJC Scopus subject areas

  • Hepatology

Cite this

Marcellin, P., Buti, M., Krastev, Z., De Man, R. A., Zeuzem, S., Lou, L., Gaggar, A., Flaherty, J. F., Massetto, B., Lin, L., Dinh, P., Subramanian, G. M., McHutchison, J. G., Flisiak, R., Gurel, S., Dusheiko, G. M., & Jenny Heathcote, E. (2014). Kinetics of hepatitis B surface antigen loss in patients with HBeAg-positive chronic hepatitis B treated with tenofovir disoproxil fumarate. Journal of Hepatology, 61(6), 1228-1237. https://doi.org/10.1016/j.jhep.2014.07.019