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

P Marcellin, M Buti, Z Krastev, Rob de Man, S Zeuzem, LL Lou, A Gaggar, JF Flaherty, B Massetto, LJ Lin, P Dinh, GM Subramanian, JG McHutchison, R Flisiak, S Gurel, GM Dusheiko, EJ 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 64 years of infection (HR = 14.3, 95% confidence interval [CI] 4.7-43.4; p < 0.0001) and an HBsAg decline of >= 1 log(10) 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-log(10) 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. (C) 2014 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
Original languageUndefined/Unknown
Pages (from-to)1228-1237
Number of pages10
JournalJournal of Hepatology
Volume61
Issue number6
Publication statusPublished - 2014

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