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

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.

• Authors: 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
• Journal: Journal of hepatology (J Hepatol) Vol. 61 Issue 6 Pg. 1228-37 (Dec 2014) ISSN: 1600-0641 [Electronic] Netherlands
• PMID: 25046847 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Chemical References

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

Topics

• Adenine (analogs & derivatives, 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, immunology)
• Humans
• Liver (enzymology)
• Longitudinal Studies
• Male
• Middle Aged
• Organophosphonates (therapeutic use)
• Regression Analysis
• Retrospective Studies
• Tenofovir
• Time Factors
• Treatment Outcome
• Young Adult