Early virologic relapse predicts alanine aminotransferase flares after nucleos(t)ide analogue withdrawal in patients with chronic hepatitis B

Kin Seng Liem, Heng Chi, Scott Fung, David K. Wong, Colina Yim, Seham Noureldin, Jiayun Chen, Robert A. de Man, Arif Sarowar, Jordan J. Feld, Bettina E. Hansen, Jinlin Hou, Jie Peng, Harry L. A. Janssen*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

When patients with chronic hepatitis B (CHB) stop nucleos(t)ide analogue (NA) ther-apy before achieving HBsAg loss, flares often ensue which are challenging to pre-dict early. We determined the incidence, severity, outcome and predictors of flares after NA withdrawal. Forty-five patients enrolled in an RCT were included; 107 pa-tients from an external, prospective cohort were used for validation. Retreatment criteria were pre- defined. Pre- and post-treatment predictors of alanine aminotrans-ferase (ALT) flare (>5× ULN) were evaluated by Cox proportional- hazards regression. Seventy-two weeks after NA withdrawal, 23/45 (51%) patients had developed >5×ULN and 14 (31%) >20× ULN. Median time to develop ALT >5× ULN was 12 weeks after NA withdrawal. Independent predictors of ALT >5× ULN were male sex (HR [95% CI] 3.2 [1.2–8.9]; p= 0.03) and serum HBV DNA (1.2 [1.0–1.8]; p= 0.03) at Week 6 off-therapy. Specifically, week 6 HBV DNA >10,000 IU/ml predicted ALT >5×ULN (3.4 [1.4–8.4]; p= 0.01), which was externally validated. In conclusion, this study on post-treatment flares revealed a high cumulative incidence in CHB. Week 6 HBV DNA >10,000 IU/ml independently predicted flares. The proposed threshold enables prediction of imminent flares in patients who may benefit from closer monitoring and earlier retreatment.
Original languageEnglish
Pages (from-to)986-993
Number of pages8
JournalJournal of Viral Hepatitis
Volume29
Issue number11
DOIs
Publication statusE-pub ahead of print - 1 Sep 2022

Bibliographical note

© 2022 John Wiley & Sons Ltd

Fingerprint

Dive into the research topics of 'Early virologic relapse predicts alanine aminotransferase flares after nucleos(t)ide analogue withdrawal in patients with chronic hepatitis B'. Together they form a unique fingerprint.

Cite this