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

J Hepatol. 2014 Dec;61(6):1228-37. doi: 10.1016/j.jhep.2014.07.019. Epub 2014 Jul 18.


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.

Keywords: Chronic hepatitis B; Hepatitis B surface antigen; Tenofovir disoproxil fumarate.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenine / analogs & derivatives*
  • Adenine / therapeutic use
  • Adolescent
  • Adult
  • Alanine Transaminase / blood
  • Antiviral Agents / therapeutic use*
  • Double-Blind Method
  • Female
  • Genotype
  • Hepatitis B Surface Antigens / blood*
  • Hepatitis B e Antigens / blood*
  • Hepatitis B virus / genetics
  • Hepatitis B, Chronic / drug therapy*
  • Hepatitis B, Chronic / immunology*
  • Humans
  • Liver / enzymology
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Organophosphonates / therapeutic use*
  • Regression Analysis
  • Retrospective Studies
  • Tenofovir
  • Time Factors
  • Treatment Outcome
  • Young Adult


  • Antiviral Agents
  • Hepatitis B Surface Antigens
  • Hepatitis B e Antigens
  • Organophosphonates
  • Tenofovir
  • Alanine Transaminase
  • Adenine