Patrick Marcellin1, Maria Buti2, Zahari Krastev3, Robert A de Man4, Stefan Zeuzem5, Lillian Lou6, Anuj Gaggar6, John F Flaherty6, Benedetta Massetto6, Lanjia Lin6, Phillip Dinh6, G Mani Subramanian6, John G McHutchison6, Robert Flisiak7, Selim Gurel8, Geoffrey M Dusheiko9, E Jenny Heathcote10. 1. Service d'Hépatologie and Inserm U773/CRB3, Hôpital Beaujon, University of Paris, Clichy, France. Electronic address: patrick.marcellin@bjn.aphp.fr. 2. Servicio de Medicina Interna Hepatologia, Hospital General Universitari Vall d'Hebron and Ciberehd, Barcelona, Spain. 3. University Hospital St. Ivan Rilsky, Sofia, Bulgaria. 4. Erasmus MC University Medical Center, Rotterdam, The Netherlands. 5. Medizinische Klinik I, Frankfurt, Germany. 6. Gilead Sciences, Foster City, CA, USA. 7. Medical University of Bialystok, Bialystok, Poland. 8. Uludag Universitesi Tip Fakultesi, Bursa, Gorukle, Turkey. 9. Royal Free Hospital, London, UK. 10. Toronto Western Hospital, University of Toronto, Toronto, Canada.
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 oftenofovir 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.
RCT Entities:
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.
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