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Tenofovir discontinuation after long-term viral suppression in HBeAg negative chronic hepatitis B. Can HBsAg levels be useful?
Maria Buti correspondence email
, Rosario Casillas
, Mar Riveiro-Barciela
, Maria Homs
, David Tabernero
, Maria Teresa Salcedo
, Francisco Rodriguez-Frias
, Rafael Esteban
Received: December 8, 2014; Received in revised form: April 30, 2015; Accepted: May 7, 2015; Published Online: May 08, 2015
Publication stage: In Press Accepted Manuscript
DOI: http://dx.doi.org/10.1016/j.jcv.2015.05.002
Highlights
•There is scarce data regarding treatment discontinuation in HBeAg-negative patients.
•We stopped TDF in 7HBeAg negative patients after 7 years of viral suppression.
•62.5% presented sustatined response after TDF discontinuation and 12.5% lost HBsAg.
•HBsAg kinetics could be useful to select patients for TDF discontinuation.
Abstract
Background
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 17HBeAg-negative patients accepted tenofovir discontinuation: 5 patients achieved sustained response (persistent HBV-DNA levels <2000 IU/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 >5000 IU/mL achieved sustained response. Patients with HBsAg level <100 IU/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.
Keywords:
TDF discontinuation, HBeAg Chronic hepatitis B, Sustained response, HBsAg levels, HBsAg loss
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发表于 2015-5-11 20:48
