title: Kinetics of hepatitis B surface antigen loss in patients with HBeAg-positive chronic hepatitis B treated with tenofovir disoproxil fumarate.
abstract: OBJECTIVE
  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.affiliation: Service d'Hépatologie and Inserm U773/CRB3, Hôpital Beaujon, University of Paris, Clichy, France. Electronic address: patrick.marcellin@bjn.aphp.fr.
authors.forename: Patrick
authors.initials: P
authors.lastname: Marcellin
authors.affiliation: Servicio de Medicina Interna Hepatologia, Hospital General Universitari Vall d'Hebron and Ciberehd, Barcelona, Spain.
authors.forename: Maria
authors.initials: M
authors.lastname: Buti
authors.affiliation: University Hospital St. Ivan Rilsky, Sofia, Bulgaria.
authors.forename: Zahari
authors.initials: Z
authors.lastname: Krastev
authors.affiliation: Erasmus MC University Medical Center, Rotterdam, The Netherlands.
authors.forename: Robert A
authors.initials: RA
authors.lastname: de Man
authors.affiliation: Medizinische Klinik I, Frankfurt, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Zeuzem
authors.affiliation: Gilead Sciences, Foster City, CA, USA.
authors.forename: Lillian
authors.initials: L
authors.lastname: Lou
authors.affiliation: Gilead Sciences, Foster City, CA, USA.
authors.forename: Anuj
authors.initials: A
authors.lastname: Gaggar
authors.affiliation: Gilead Sciences, Foster City, CA, USA.
authors.forename: John F
authors.initials: JF
authors.lastname: Flaherty
authors.affiliation: Gilead Sciences, Foster City, CA, USA.
authors.forename: Benedetta
authors.initials: B
authors.lastname: Massetto
authors.affiliation: Gilead Sciences, Foster City, CA, USA.
authors.forename: Lanjia
authors.initials: L
authors.lastname: Lin
authors.affiliation: Gilead Sciences, Foster City, CA, USA.
authors.forename: Phillip
authors.initials: P
authors.lastname: Dinh
authors.affiliation: Gilead Sciences, Foster City, CA, USA.
authors.forename: G Mani
authors.initials: GM
authors.lastname: Subramanian
authors.affiliation: Gilead Sciences, Foster City, CA, USA.
authors.forename: John G
authors.initials: JG
authors.lastname: McHutchison
authors.affiliation: Medical University of Bialystok, Bialystok, Poland.
authors.forename: Robert
authors.initials: R
authors.lastname: Flisiak
authors.affiliation: Uludag Universitesi Tip Fakultesi, Bursa, Gorukle, Turkey.
authors.forename: Selim
authors.initials: S
authors.lastname: Gurel
authors.affiliation: Royal Free Hospital, London, UK.
authors.forename: Geoffrey M
authors.initials: GM
authors.lastname: Dusheiko
authors.affiliation: Toronto Western Hospital, University of Toronto, Toronto, Canada.
authors.forename: E Jenny
authors.initials: EJ
authors.lastname: Heathcote
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000293:Adolescent; D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D000998:Antiviral Agents / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D005838:Genotype; D006514:Hepatitis B Surface Antigens / Q000097:blood*; D006513:Hepatitis B e Antigens / Q000097:blood*; D006515:Hepatitis B virus / Q000235:genetics; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000276:immunology*; D006801:Humans; D008099:Liver / Q000201:enzymology; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D063065:Organophosphonates / Q000627:therapeutic use*; D012044:Regression Analysis; D012189:Retrospective Studies; D000068698:Tenofovir; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D006514:Hepatitis B Surface Antigens; D006513:Hepatitis B e Antigens; D063065:Organophosphonates; D000068698:Tenofovir; D000410:Alanine Transaminase; D000225:Adenine
keywords: Chronic hepatitis B; Hepatitis B surface antigen; Tenofovir disoproxil fumarate