TY - JOUR
T1 - The times they are a-changing – A refined proposal for finite HBV nucleos(t)ide analogue therapy
AU - Berg, Thomas
AU - Lampertico, Pietro
N1 - Funding Information:
We would like to thank Dr. Toni Herta for his help in designing the figure and Dr. Florian van B?mmel for carefully reading the manuscript and his helpful comments.
Publisher Copyright:
© 2021 European Association for the Study of the Liver
PY - 2021
Y1 - 2021
N2 - Although discontinuation of nucleos(t)ide analogue (NA) treatment before HBsAg loss is part of all current HBV treatment guidelines for HBeAg-positive patients who achieve HBeAg seroconversion, a treatment endpoint known to be associated with silencing of HBV transcriptional activity and restoration of HBV-specific immune control, whether it is even appropriate to consider NA discontinuation before HBsAg loss in the HBeAg-negative phase remains highly controversial. Despite the growing evidence that a relevant, albeit small, proportion of patients with HBeAg-negative disease can be cured by stopping NA treatment, the fear of discontinuation-associated relapse and the uncertainty of how to predict off-therapy response and monitor patients after discontinuation have generated scepticism and subsequently led to low implementation of this concept in the clinic. In this article, we propose a concept in which NA discontinuation-associated relapse is an integral part of the stop-to-cure approach and ultimately the trigger for achieving HBsAg loss. However, the relapse in this sense becomes functionally effective only if HBV-specific immune reinvigoration and silencing of HBV transcriptional activity have been achieved during the NA treatment period. The probability of functional cure and the severity of post-discontinuation flares depend on the underlying baseline transcriptional activity of HBV when NA therapy was started, as well as the duration of NA treatment, both factors that should be considered as we move towards individualised approaches to HBV cure.
AB - Although discontinuation of nucleos(t)ide analogue (NA) treatment before HBsAg loss is part of all current HBV treatment guidelines for HBeAg-positive patients who achieve HBeAg seroconversion, a treatment endpoint known to be associated with silencing of HBV transcriptional activity and restoration of HBV-specific immune control, whether it is even appropriate to consider NA discontinuation before HBsAg loss in the HBeAg-negative phase remains highly controversial. Despite the growing evidence that a relevant, albeit small, proportion of patients with HBeAg-negative disease can be cured by stopping NA treatment, the fear of discontinuation-associated relapse and the uncertainty of how to predict off-therapy response and monitor patients after discontinuation have generated scepticism and subsequently led to low implementation of this concept in the clinic. In this article, we propose a concept in which NA discontinuation-associated relapse is an integral part of the stop-to-cure approach and ultimately the trigger for achieving HBsAg loss. However, the relapse in this sense becomes functionally effective only if HBV-specific immune reinvigoration and silencing of HBV transcriptional activity have been achieved during the NA treatment period. The probability of functional cure and the severity of post-discontinuation flares depend on the underlying baseline transcriptional activity of HBV when NA therapy was started, as well as the duration of NA treatment, both factors that should be considered as we move towards individualised approaches to HBV cure.
KW - ALT flares
KW - functional cure
KW - HBeAg-negative CHB
KW - HBsAg loss
KW - NA discontinuation
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U2 - 10.1016/j.jhep.2021.04.040
DO - 10.1016/j.jhep.2021.04.040
M3 - Review article
C2 - 33957187
AN - SCOPUS:85106615083
VL - 75
SP - 474
EP - 480
JO - Journal of Hepatology
JF - Journal of Hepatology
SN - 0168-8278
IS - 2
ER -