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

doi:10.1111/jvh.13742

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 journal › Article › Academic › peer-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 language	English
Pages (from-to)	986-993
Number of pages	8
Journal	Journal of Viral Hepatitis
Volume	29
Issue number	11
DOIs	https://doi.org/10.1111/jvh.13742
Publication status	E-pub ahead of print - 1 Sep 2022

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Liem, K. S., Chi, H., Fung, S., Wong, D. K., Yim, C., Noureldin, S., Chen, J., de Man, R. A., Sarowar, A., Feld, J. J., Hansen, B. E., Hou, J., Peng, J., & Janssen, H. L. A. (2022). Early virologic relapse predicts alanine aminotransferase flares after nucleos(t)ide analogue withdrawal in patients with chronic hepatitis B. Journal of Viral Hepatitis, 29(11), 986-993. https://doi.org/10.1111/jvh.13742

@article{515f809e56314e43b9d5904f9fc4b583,

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

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.",

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

note = "{\textcopyright} 2022 John Wiley & Sons Ltd",

year = "2022",

month = sep,

day = "1",

doi = "10.1111/jvh.13742",

language = "English",

volume = "29",

pages = "986--993",

journal = "Journal of Viral Hepatitis",

issn = "1352-0504",

publisher = "Wiley-Blackwell Publishing Ltd",

number = "11",

}

Liem, KS, Chi, H, Fung, S, Wong, DK, Yim, C, Noureldin, S, Chen, J, de Man, RA, Sarowar, A, Feld, JJ, Hansen, BE, Hou, J, Peng, J & Janssen, HLA 2022, 'Early virologic relapse predicts alanine aminotransferase flares after nucleos(t)ide analogue withdrawal in patients with chronic hepatitis B', Journal of Viral Hepatitis, vol. 29, no. 11, pp. 986-993. https://doi.org/10.1111/jvh.13742

TY - JOUR

T1 - Early virologic relapse predicts alanine aminotransferase flares after nucleos(t)ide analogue withdrawal in patients with chronic hepatitis B

AU - Liem, Kin Seng

AU - Chi, Heng

AU - Fung, Scott

AU - Wong, David K.

AU - Yim, Colina

AU - Noureldin, Seham

AU - Chen, Jiayun

AU - de Man, Robert A.

AU - Sarowar, Arif

AU - Feld, Jordan J.

AU - Hansen, Bettina E.

AU - Hou, Jinlin

AU - Peng, Jie

AU - Janssen, Harry L. A.

PY - 2022/9/1

Y1 - 2022/9/1

N2 - 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.

AB - 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.

U2 - 10.1111/jvh.13742

DO - 10.1111/jvh.13742

M3 - Article

VL - 29

SP - 986

EP - 993

JO - Journal of Viral Hepatitis

JF - Journal of Viral Hepatitis

SN - 1352-0504

IS - 11

ER -

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

Abstract

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