HBsAg decline and clearance with peg-IFN therapy added to nucleos(t)ide analogues: an individual participant data meta-analysis of prospective trials (PROSPER)

Edo J Dongelmans; Lesley A Patmore; Seng Gee Lim; Marc Bourliere; Shaowen Jiang; Nathalie Ganne-Carrie; Willem-Pieter Brouwer; Jordan J Feld; Yuxian Huang; Jose A Carrion; Teresa Broquetas; Qiankun Hu; Scott Fung; Fabrice Carrat; Fabien Zoulim; Bettina E Hansen; Qing Xie; Harry L A Janssen; Milan J Sonneveld

doi:10.1136/gutjnl-2025-336251

HBsAg decline and clearance with peg-IFN therapy added to nucleos(t)ide analogues: an individual participant data meta-analysis of prospective trials (PROSPER)

Edo J Dongelmans^*
, Lesley A Patmore
, Seng Gee Lim
, Marc Bourliere
, Shaowen Jiang
, Nathalie Ganne-Carrie
, Willem-Pieter Brouwer
, Jordan J Feld
, Yuxian Huang
, Jose A Carrion
, Teresa Broquetas
, Qiankun Hu
, Scott Fung
, Fabrice Carrat
, Fabien Zoulim
, Bettina E Hansen
, Qing Xie
, Harry L A Janssen
, Milan J Sonneveld

^*Corresponding author for this work

Erasmus University Medical Centre
National University Health System
Hepatology and Gastroenterology Unit - Liver Unit
Shanghai Jiao Tong University School of Medicine
Service d'Hépatologie
University Health Network
Fudan University
Hospital del Mar
Sorbonne Université
Lyon Hepatology Institute (IHU EVEREST)
Toronto General Hospital
University of Toronto

Research output: Contribution to journal › Article › Academic › peer-review

3 Citations (Scopus)

2 Downloads (Pure)

Abstract

BACKGROUND:

Peg-interferon (peg-IFN) plays an increasingly important role in HBV cure strategies, either in combination with novel antivirals, as a lead-in or as consolidation treatment.

OBJECTIVE:

We aimed to provide estimates of hepatitis B surface antigen (HBsAg) decline and clearance that can be achieved with peg-IFN addition to nucleos(t)ide analogue (NA) therapy.

DESIGN:

This is a post hoc meta-analysis of individual participant data from eight clinical trials involving chronic hepatitis B patients on NA therapy who received peg-IFN add-on. The primary endpoint was HBsAg loss at end of follow-up (EOF, 6-12 months after end of peg-IFN). Secondary analyses focused on HBsAg decline.

RESULTS:

581 patients were included. At the start of peg-IFN therapy (SOT), 44% were hepatitis B envelope antigen (HBeAg) positive, mean HBsAg level was 3.03 log10 IU/mL (HBsAg<100: 12%; 100-1000: 28%; ≥1000: 60%), and planned duration of peg-IFN was 48 weeks in 496 patients (85%).At EOF, 50 (8.6%) patients achieved HBsAg loss (HBsAg<100/100-1000/≥1000: 37.7/9.8/2.3%, p<0.001) Findings were consistent across ethnicities (Caucasian: 30.0/8.7/3.6%; Asian: 39.3/9.2/2.2%). In patients with SOT HBsAg≥1000 IU/mL, levels <1000 and <100 were achieved in 29.7% and 8.9% at 24 weeks and in 47.5% and 16.3% at 48 weeks of peg-IFN therapy, respectively.

CONCLUSION:

Peg-IFN add-on results in HBsAg loss in 18% of patients with SOT HBsAg<1000 IU/mL, and in 38% if SOT HBsAg<100 IU/mL. Among patients with higher HBsAg levels, peg-IFN could be used to reduce HBsAg to below thresholds associated with response to novel compounds.

Original language	English
Article number	gutjnl-2025-336251
Journal	Gut
Early online date	5 Nov 2025
DOIs	https://doi.org/10.1136/gutjnl-2025-336251
Publication status	E-pub ahead of print - 5 Nov 2025

Bibliographical note

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Access to Document

10.1136/gutjnl-2025-336251Licence: CC BY-NC

HBsAg decline and clearance with peg-IFN therapy added to nucleos(t)ide analoguesFinal published version, 1.25 MBLicence: CC BY-NC

Cite this

Dongelmans, E. J., Patmore, L. A., Lim, S. G., Bourliere, M., Jiang, S., Ganne-Carrie, N., Brouwer, W.-P., Feld, J. J., Huang, Y., Carrion, J. A., Broquetas, T., Hu, Q., Fung, S., Carrat, F., Zoulim, F., Hansen, B. E., Xie, Q., Janssen, H. L. A., & Sonneveld, M. J. (2025). HBsAg decline and clearance with peg-IFN therapy added to nucleos(t)ide analogues: an individual participant data meta-analysis of prospective trials (PROSPER). Gut, Article gutjnl-2025-336251. Advance online publication. https://doi.org/10.1136/gutjnl-2025-336251

@article{c6f6ff59760b44ddbc961569e29b0945,

title = "HBsAg decline and clearance with peg-IFN therapy added to nucleos(t)ide analogues: an individual participant data meta-analysis of prospective trials (PROSPER)",

abstract = "BACKGROUND: Peg-interferon (peg-IFN) plays an increasingly important role in HBV cure strategies, either in combination with novel antivirals, as a lead-in or as consolidation treatment.OBJECTIVE: We aimed to provide estimates of hepatitis B surface antigen (HBsAg) decline and clearance that can be achieved with peg-IFN addition to nucleos(t)ide analogue (NA) therapy.DESIGN: This is a post hoc meta-analysis of individual participant data from eight clinical trials involving chronic hepatitis B patients on NA therapy who received peg-IFN add-on. The primary endpoint was HBsAg loss at end of follow-up (EOF, 6-12 months after end of peg-IFN). Secondary analyses focused on HBsAg decline.RESULTS: 581 patients were included. At the start of peg-IFN therapy (SOT), 44\% were hepatitis B envelope antigen (HBeAg) positive, mean HBsAg level was 3.03 log10 IU/mL (HBsAg<100: 12\%; 100-1000: 28\%; ≥1000: 60\%), and planned duration of peg-IFN was 48 weeks in 496 patients (85\%).At EOF, 50 (8.6\%) patients achieved HBsAg loss (HBsAg<100/100-1000/≥1000: 37.7/9.8/2.3\%, p<0.001) Findings were consistent across ethnicities (Caucasian: 30.0/8.7/3.6\%; Asian: 39.3/9.2/2.2\%). In patients with SOT HBsAg≥1000 IU/mL, levels <1000 and <100 were achieved in 29.7\% and 8.9\% at 24 weeks and in 47.5\% and 16.3\% at 48 weeks of peg-IFN therapy, respectively.CONCLUSION: Peg-IFN add-on results in HBsAg loss in 18\% of patients with SOT HBsAg<1000 IU/mL, and in 38\% if SOT HBsAg<100 IU/mL. Among patients with higher HBsAg levels, peg-IFN could be used to reduce HBsAg to below thresholds associated with response to novel compounds.",

author = "Dongelmans, \{Edo J\} and Patmore, \{Lesley A\} and Lim, \{Seng Gee\} and Marc Bourliere and Shaowen Jiang and Nathalie Ganne-Carrie and Willem-Pieter Brouwer and Feld, \{Jordan J\} and Yuxian Huang and Carrion, \{Jose A\} and Teresa Broquetas and Qiankun Hu and Scott Fung and Fabrice Carrat and Fabien Zoulim and Hansen, \{Bettina E\} and Qing Xie and Janssen, \{Harry L A\} and Sonneveld, \{Milan J\}",

note = "{\textcopyright} Author(s) (or their employer(s)) 2025. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group.",

year = "2025",

month = nov,

day = "5",

doi = "10.1136/gutjnl-2025-336251",

language = "English",

journal = "Gut",

issn = "0017-5749",

publisher = "BMJ Publishing Group",

}

Dongelmans, EJ, Patmore, LA, Lim, SG, Bourliere, M, Jiang, S, Ganne-Carrie, N, Brouwer, W-P, Feld, JJ, Huang, Y, Carrion, JA, Broquetas, T, Hu, Q, Fung, S, Carrat, F, Zoulim, F, Hansen, BE, Xie, Q, Janssen, HLA & Sonneveld, MJ 2025, 'HBsAg decline and clearance with peg-IFN therapy added to nucleos(t)ide analogues: an individual participant data meta-analysis of prospective trials (PROSPER)', Gut. https://doi.org/10.1136/gutjnl-2025-336251

TY - JOUR

T1 - HBsAg decline and clearance with peg-IFN therapy added to nucleos(t)ide analogues

T2 - an individual participant data meta-analysis of prospective trials (PROSPER)

AU - Dongelmans, Edo J

AU - Patmore, Lesley A

AU - Lim, Seng Gee

AU - Bourliere, Marc

AU - Jiang, Shaowen

AU - Ganne-Carrie, Nathalie

AU - Brouwer, Willem-Pieter

AU - Feld, Jordan J

AU - Huang, Yuxian

AU - Carrion, Jose A

AU - Broquetas, Teresa

AU - Hu, Qiankun

AU - Fung, Scott

AU - Carrat, Fabrice

AU - Zoulim, Fabien

AU - Hansen, Bettina E

AU - Xie, Qing

AU - Janssen, Harry L A

AU - Sonneveld, Milan J

PY - 2025/11/5

Y1 - 2025/11/5

N2 - BACKGROUND: Peg-interferon (peg-IFN) plays an increasingly important role in HBV cure strategies, either in combination with novel antivirals, as a lead-in or as consolidation treatment.OBJECTIVE: We aimed to provide estimates of hepatitis B surface antigen (HBsAg) decline and clearance that can be achieved with peg-IFN addition to nucleos(t)ide analogue (NA) therapy.DESIGN: This is a post hoc meta-analysis of individual participant data from eight clinical trials involving chronic hepatitis B patients on NA therapy who received peg-IFN add-on. The primary endpoint was HBsAg loss at end of follow-up (EOF, 6-12 months after end of peg-IFN). Secondary analyses focused on HBsAg decline.RESULTS: 581 patients were included. At the start of peg-IFN therapy (SOT), 44% were hepatitis B envelope antigen (HBeAg) positive, mean HBsAg level was 3.03 log10 IU/mL (HBsAg<100: 12%; 100-1000: 28%; ≥1000: 60%), and planned duration of peg-IFN was 48 weeks in 496 patients (85%).At EOF, 50 (8.6%) patients achieved HBsAg loss (HBsAg<100/100-1000/≥1000: 37.7/9.8/2.3%, p<0.001) Findings were consistent across ethnicities (Caucasian: 30.0/8.7/3.6%; Asian: 39.3/9.2/2.2%). In patients with SOT HBsAg≥1000 IU/mL, levels <1000 and <100 were achieved in 29.7% and 8.9% at 24 weeks and in 47.5% and 16.3% at 48 weeks of peg-IFN therapy, respectively.CONCLUSION: Peg-IFN add-on results in HBsAg loss in 18% of patients with SOT HBsAg<1000 IU/mL, and in 38% if SOT HBsAg<100 IU/mL. Among patients with higher HBsAg levels, peg-IFN could be used to reduce HBsAg to below thresholds associated with response to novel compounds.

AB - BACKGROUND: Peg-interferon (peg-IFN) plays an increasingly important role in HBV cure strategies, either in combination with novel antivirals, as a lead-in or as consolidation treatment.OBJECTIVE: We aimed to provide estimates of hepatitis B surface antigen (HBsAg) decline and clearance that can be achieved with peg-IFN addition to nucleos(t)ide analogue (NA) therapy.DESIGN: This is a post hoc meta-analysis of individual participant data from eight clinical trials involving chronic hepatitis B patients on NA therapy who received peg-IFN add-on. The primary endpoint was HBsAg loss at end of follow-up (EOF, 6-12 months after end of peg-IFN). Secondary analyses focused on HBsAg decline.RESULTS: 581 patients were included. At the start of peg-IFN therapy (SOT), 44% were hepatitis B envelope antigen (HBeAg) positive, mean HBsAg level was 3.03 log10 IU/mL (HBsAg<100: 12%; 100-1000: 28%; ≥1000: 60%), and planned duration of peg-IFN was 48 weeks in 496 patients (85%).At EOF, 50 (8.6%) patients achieved HBsAg loss (HBsAg<100/100-1000/≥1000: 37.7/9.8/2.3%, p<0.001) Findings were consistent across ethnicities (Caucasian: 30.0/8.7/3.6%; Asian: 39.3/9.2/2.2%). In patients with SOT HBsAg≥1000 IU/mL, levels <1000 and <100 were achieved in 29.7% and 8.9% at 24 weeks and in 47.5% and 16.3% at 48 weeks of peg-IFN therapy, respectively.CONCLUSION: Peg-IFN add-on results in HBsAg loss in 18% of patients with SOT HBsAg<1000 IU/mL, and in 38% if SOT HBsAg<100 IU/mL. Among patients with higher HBsAg levels, peg-IFN could be used to reduce HBsAg to below thresholds associated with response to novel compounds.

UR - https://www.scopus.com/pages/publications/105021226742

U2 - 10.1136/gutjnl-2025-336251

DO - 10.1136/gutjnl-2025-336251

M3 - Article

C2 - 41198171

SN - 0017-5749

JO - Gut

JF - Gut

M1 - gutjnl-2025-336251

ER -

HBsAg decline and clearance with peg-IFN therapy added to nucleos(t)ide analogues: an individual participant data meta-analysis of prospective trials (PROSPER)

Abstract

Bibliographical note

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this