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J Clin Virol. 2015 Jul;68:61-8. doi: 10.1016/j.jcv.2015.05.002. Epub 2015 May 8.
Tenofovir discontinuation after long-term viral suppression in HBeAg negative chronic hepatitis B. Can HBsAg levels be useful?Buti M1, Casillas R2, Riveiro-Barciela M2, Homs M3, Tabernero D3, Salcedo MT4, Rodriguez-Frias F3, Esteban R5.
Author information
- 1Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain; Liver Unit, Department of Internal Medicine, Hospital Universitari Vall d'Hebron and Universitat Autònoma de Barcelona, Barcelona, Spain. Electronic address: [email protected].
- 2Liver Unit, Department of Internal Medicine, Hospital Universitari Vall d'Hebron and Universitat Autònoma de Barcelona, Barcelona, Spain.
- 3Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain; Liver Pathology Unit, Departments of Biochemistry and Microbiology (Virology Unit) Hospital Universitari Vall d'Hebron and Universitat Autònoma de Barcelona, Barcelona, Spain.
- 4Pathology Department, Hospital Universitari Vall d'Hebron and Universitat Autònoma de Barcelona, Barcelona 08035, Spain.
- 5Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain; Liver Unit, Department of Internal Medicine, Hospital Universitari Vall d'Hebron and Universitat Autònoma de Barcelona, Barcelona, Spain.
AbstractBACKGROUND: Recent studies have shown that antiviral treatment discontinuation is safe and associated with virologic remission in HBeAg-negative patients. However, the period of viral suppression and follow-up in these studies was relatively short.
OBJECTIVES: To investigate whether continuous viral suppression with tenofovir disoproxil fumarate for more than 7 years is associated with HBsAg loss and sustained response after treatment discontinuation and receiving a full course of hepatitis B vaccination.
STUDY DESIGN: Patients with HBeAg-negative chronic HBV infection and more than 7 years of persistent viral suppression with tenofovir therapy were selected for treatment discontinuation and HBV vaccination. Follow-up with monthly ALT, HBV-DNA, and HBsAg determinations lasted 72 weeks. In patients with viral relapse, the viral quasispecies in the overlapping reverse transcriptase and small surface protein regions was analysed by ultra-deep pyrosequencing.
RESULTS: Eight of 17 HBeAg-negative patients accepted tenofovir discontinuation: 5 patients achieved sustained response (persistent HBV-DNA levels <2000IU/mL and normal ALT) despite an initial virologic relapse, one lost HBsAg, and two needed re-treatment. All patients with an on-treatment HBsAg level decline >5000IU/mL achieved sustained response. Patients with HBsAg level <100IU/mL during an ALT flare after antiviral discontinuation achieved sustained response. Significant changes were seen in the composition of the HBV quasispecies, and half the patients showed changes in HBV genotype.
CONCLUSIONS: Even though the majority of patients presented an initial relapse with selection of HBV variants, most achieved sustained response. Changes in HBsAg levels on and off treatment may be useful for predicting the likelihood of virologic remission.
Copyright © 2015 Elsevier B.V. All rights reserved.
KEYWORDS: HBeAg chronic hepatitis B; HBsAg levels; HBsAg loss; Sustained response; TDF discontinuation
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