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

2 Citations (Scopus)


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
Issue number11
Early online date1 Sept 2022
Publication statusPublished - Nov 2022

Bibliographical note

Funding Information:
The investigator‐initiated study (cohort 1) was organized and sponsored by University Health Network (Toronto, Canada). Gilead Sciences, Inc. (Foster City, US) has provided funding support and study medication for patients who required but did not have access to TDF. The validation cohort study (cohort 2) was supported by National Natural Science Foundation of China (81971949). Funding sources did not have any influence on study design, data collection, analysis and interpretation of data, writing of the report or the decision to submit for publication.

Funding Information:
B.E. Hansen has received grants from and is a consultant to Intercept Pharmaceuticals. H.L.A. Janssen has received grants from and is a consultant to Abbott, Bristol‐Myers Squibb, Gilead Sciences, Merck, Novartis, Roche and Janssen. J. Feld reports receiving support for research or scientific consulting from Abbott, Abbvie, Contavir, Enanta, Gilead Sciences, Janssen and Roche. J. Hou has received consulting fee from AbbVie, Arbutus, Bristol Myers Squibb, Gilead Sciences, Johnson &Johnson, Roche and received grants from Bristol Myers Squibb and Johnson &Johnson. S. Fung has received research support from Gilead Sciences and speaking & teaching and/or consulting fees from Gilead Sciences, Merck and AbbVie. D. Wong has received speaking & teaching fees from AbbVie and Merck. Colina Yim has received an educational grant from Gilead Sciences. All other authors have nothing to disclose.

Publisher Copyright:
© 2022 John Wiley & Sons Ltd.


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