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

JOURNAL OF HEPATOLOGY

卷:61

Article

Marcellin, Patrick^1,2  Buti, Maria³  Krastev, Zahari⁴  de Man, Robert A.⁵  Zeuzem, Stefan⁶  Lou, Lillian⁷  Gaggar, Anuj⁷  Flaherty, John F.⁷  Massetto, Benedetta⁷  Lin, Lanjia⁷  Dinh, Phillip⁷  Subramanian, G. Mani⁷  McHutchison, John G.⁷  Flisiak, Robert⁸  Gurel, Selim⁹  Dusheiko, Geoffrey M.¹⁰  Heathcote, E. Jenny¹¹ 

[1] Univ Paris, Hop Beaujon, Serv Hepatol, Clichy, France

[2] Univ Paris, Hop Beaujon, INSERM, CRB3,U773, Clichy, France

[3] Univ Vall Hebron & Ciberehd, Gen Hosp, Serv Med Interna Hepatol, Barcelona, Spain

[4] Univ Hosp St Ivan Rilsky, Sofia, Bulgaria

[5] Univ Med Ctr, Erasmus MC, Rotterdam, Netherlands

[6] Med Klin 1, Frankfurt, Germany

[7] Gilead Sci, Foster City, CA USA

[8] Med Univ Bialystok, Bialystok, Poland

[9] Uludag Univ, Tip Fak, Gorukle, Turkey

[10] Royal Free Hosp, London NW3 2QG, England

[11] Univ Toronto, Toronto Western Hosp, Toronto, ON M5T 2S8, Canada

关键词: Chronic hepatitis B;    Hepatitis B surface antigen;    Tenofovir disoproxil fumarate;   

DOI  :  10.1016/j.jhep.2014.07.019

来源: Elsevier

【 摘 要 】

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.

【 授权许可】

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