Funding: This work was funded by the National Natural Science Foundation of China, grant number (82103861) and the Natural Science Foundation of Hunan Province, China (2024JJ5457).

Shuangjie Li and Wenxian Ouyang contributed equally to this paper.

Handling Editor: Luca Valenti

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ABSTRACT

Background and Aims

Achieving HBsAg loss is a critical clinical milestone in the management of chronic hepatitis B (CHB) towards the eradication of hepatitis B. However, there are limited researches on the incidence and determinants of HBsAg loss in paediatric CHB patients undergoing antiviral treatment. Therefore, we aimed to analyse the incidence and potential determinants of HBsAg loss in children who suffered from CHB and received antiviral treatment.

Methods

This retrospective cohort study was performed on paediatric patients with progressive CHB who initiated either monotherapy or combination therapy using interferon/peg-interferon and entecavir. We utilised Cox regression models to evaluate the relationships between HBsAg loss and various determining factors.

Results

In total of 306 subjects with an average age of 4.99 years (range 1–15) were identified in this study, of whom 200 (65.4%) were male. After a median follow-up of 26 months, HBsAg loss occurred in 135 participants. The accumulated rate of HBsAg loss was 67.8% at the end of the follow-up evaluation. Multivariate Cox regression analysis revealed that older age (HR = 0.84, 95% CI: 0.79–0.90), female sex (HR = 1.61, 95% CI: 1.13–2.30), baseline HBsAg levels (HR = 0.72, 95% CI: 0.62–0.84), HBsAb positivity (HR = 1.77, 95% CI: 1.20–2.59) and serum bilirubin levels (HR = 0.96, 95% CI: 0.92–0.99) were statistically significant predictors of HBsAg loss.

Conclusion

The incidence of HBsAg loss continues to increase in paediatric patients with CHB after antiviral treatment. Age, sex, baseline HBsAg and bilirubin levels and HBsAb positivity are found to be associated with sustained HBsAg loss.

Conflicts of Interest

The authors declare no conflicts of interest.

Open Research

Data Availability Statement

The data that support the findings of this study are available on request from the corresponding author.

References

1W. J. Jeng, G. V. Papatheodoridis, and A. S. F. Lok, “Hepatitis B,” Lancet 401, no. 10381 (2023): 1039–1052.
10.1016/S0140-6736(22)01468-4
CAS PubMed Web of Science® Google Scholar
2K. A. McGlynn, J. L. Petrick, and H. B. El-Serag, “Epidemiology of Hepatocellular Carcinoma,” Hepatology 73, no. Suppl 1 (2021): 4–13.
10.1002/hep.31288
CAS PubMed Web of Science® Google Scholar
3J. M. Llovet, R. K. Kelley, A. Villanueva, et al., “Hepatocellular Carcinoma,” Nature Reviews Disease Primers 7, no. 1 (2021): 6.
10.1038/s41572-020-00240-3
PubMed Web of Science® Google Scholar
4G. L. H. Wong, E. Gane, and A. S. F. Lok, “How to Achieve Functional Cure of HBV: Stopping NUCs, Adding Interferon or New Drug Development?,” Journal of Hepatology 76, no. 6 (2022): 1249–1262.
10.1016/j.jhep.2021.11.024
CAS PubMed Web of Science® Google Scholar
5C. S. Coffin, S. Haylock-Jacobs, K. Doucette, et al., “Clinical Outcomes and Quantitative HBV Surface Antigen Levels in Diverse Chronic Hepatitis B Patients in Canada: A Retrospective Real-World Study of CHB in Canada (REVEAL-Canada),” Viruses 14, no. 12 (2022): 2668.
10.3390/v14122668
CAS PubMed Google Scholar
6Y. C. Hsu, D. W. Jun, C. Y. Peng, et al., “Effectiveness of Entecavir vs Tenofovir Disoproxil Fumarate for Functional Cure of Chronic Hepatitis B in an International Cohort,” Hepatology International 16, no. 6 (2022): 1297–1307.
10.1007/s12072-022-10411-x
PubMed Web of Science® Google Scholar
7M. J. Sonneveld, S. M. Chiu, J. Y. Park, et al., “Probability of HBsAg Loss After Nucleo(s)tide Analogue Withdrawal Depends on HBV Genotype and Viral Antigen Levels,” Journal of Hepatology 76, no. 5 (2022): 1042–1050.
10.1016/j.jhep.2022.01.007
CAS PubMed Web of Science® Google Scholar
8N. A. Terrault, A. S. Lok, A. S. Wahed, et al., “Randomized Trial of Tenofovir With or Without Peginterferon Alfa Followed by Protocolized Treatment Withdrawal in Adults With Chronic Hepatitis B,” American Journal of Gastroenterology 118, no. 7 (2023): 1214–1225.
10.14309/ajg.0000000000002125
CAS PubMed Web of Science® Google Scholar
9Y. C. Hsu, M. L. Yeh, G. L. Wong, et al., “Incidences and Determinants of Functional Cure During Entecavir or Tenofovir Disoproxil Fumarate for Chronic Hepatitis B,” Journal of Infectious Diseases 224, no. 11 (2021): 1890–1899.
10.1093/infdis/jiab241
CAS PubMed Web of Science® Google Scholar
10N. A. Terrault, A. S. Wahed, J. J. Feld, et al., “Incidence and Prediction of HBsAg Seroclearance in a Prospective Multi-Ethnic HBeAg-Negative Chronic Hepatitis B Cohort,” Hepatology 75, no. 3 (2022): 709–723.
10.1002/hep.32231
CAS PubMed Web of Science® Google Scholar
11M. J. Sonneveld, S. M. Chiu, J. Y. Park, et al., “Lower Pretreatment HBV DNA Levels Are Associated With Better Off-Treatment Outcomes After Nucleo(s)tide Analogue Withdrawal in Patients With HBeAg-Negative Chronic Hepatitis B: A Multicentre Cohort Study,” JHEP Reports 5, no. 8 (2023): 100790.
10.1016/j.jhepr.2023.100790
PubMed Google Scholar
12Y. Xie, M. Li, X. Ou, et al., “Lower End of Treatment HBsAg and HBcrAg Were Associated With HBsAg Loss After Nucleos(t)ide Analog Cessation,” BMC Gastroenterology 23, no. 1 (2023): 224.
10.1186/s12876-023-02852-x
CAS PubMed Web of Science® Google Scholar
13J. Pan, H. Wang, T. Yao, et al., “Clinical Predictors of Functional Cure in Children 1–6 Years-Old With Chronic Hepatitis B,” Journal of Clinical and Translational Hepatology 10, no. 3 (2022): 405–411.
10.14218/JCTH.2021.00142
PubMed Web of Science® Google Scholar
14D. Wong, M. Littlejohn, R. Edwards, et al., “ALT Flares During Nucleotide Analogue Therapy Are Associated With HBsAg Loss in Genotype A HBeAg-Positive Chronic Hepatitis B,” Liver International 38, no. 10 (2018): 1760–1769.
10.1111/liv.13716
CAS PubMed Web of Science® Google Scholar
15H. You, F. Wang, T. Li, et al., “Guidelines for the Prevention and Treatment for Chronic Hepatitis B (2022 Version),” Chinese Journal of Hepatology 30, no. 12 (2022): 1309–1331.
Google Scholar
16G. Samadi Kochaksaraei, E. Castillo, M. D. Sadler, et al., “Real-World Clinical and Virological Outcomes in a Retrospective Multiethnic Cohort Study of 341 Untreated and Tenofovir Disoproxil Fumarate-Treated Chronic Hepatitis B Pregnant Patients in North America,” Alimentary Pharmacology & Therapeutics 52, no. 11–12 (2020): 1707–1716.
10.1111/apt.16123
CAS PubMed Web of Science® Google Scholar
17L. Wang, J. Zhao, J. Liu, et al., “Long-Term Benefits of Interferon-α Therapy in Children With HBeAg-Positive Immune-Active Chronic Hepatitis B,” Journal of Viral Hepatitis 28, no. 11 (2021): 1554–1562.
10.1111/jvh.13598
CAS PubMed Web of Science® Google Scholar
18M. Li, Q. Li, J. Qu, et al., “The Effectiveness of Combination Therapy With Interferon and Nucleoside Analogs in Pediatric Patients With Chronic Hepatitis B: A Systematic Review and Meta-Analysis,” Hepatology International 17, no. 1 (2023): 52–62.
10.1007/s12072-022-10415-7
PubMed Web of Science® Google Scholar
19X. Wu, Z. Yao, X. Lai, Y. Gu, and S. Peng, “Age at Treatment Initiation Predicts Response in Children With Chronic Hepatitis B,” Alimentary Pharmacology & Therapeutics 58 (2023): 866–873.
10.1111/apt.17667
CAS PubMed Web of Science® Google Scholar
20T. C. Tseng, C. J. Liu, C. L. Chen, et al., “Higher Lifetime Chance of Spontaneous Surface Antigen Loss in Hepatitis B Carriers With Genotype C Infection,” Alimentary Pharmacology & Therapeutics 41, no. 10 (2015): 949–960.
10.1111/apt.13170
PubMed Web of Science® Google Scholar
21W. X. Wang, R. Jia, Y. Y. Gao, et al., “Quantitative Anti-HBc Combined With Quantitative HBsAg Can Predict HBsAg Clearance in Sequential Combination Therapy With PEG-IFN-α in NA-Suppressed Chronic Hepatitis B Patients,” Frontiers in Immunology 13 (2022): 894410.
10.3389/fimmu.2022.894410
CAS PubMed Google Scholar
22M. Du, S. Zhang, L. Xiao, et al., “The Relationship Between Serum Bilirubin and Elevated Fibrotic Indices Among HBV Carriers: A Cross-Sectional Study of a Chinese Population,” International Journal of Molecular Sciences 17, no. 12 (2016): 2057.
10.3390/ijms17122057
PubMed Web of Science® Google Scholar
23Z. Xun, C. Liu, Q. Q. Yu, et al., “Albumin-Bilirubin Score Is Associated With Response to Pegylated Interferon and Nucleos(t)ide Analogues in Chronic Hepatitis B Patients,” Clinica Chimica Acta 502 (2020): 120–127.
10.1016/j.cca.2019.12.020
CAS PubMed Web of Science® Google Scholar
24X. B. Gu, X. J. Yang, D. Wang, Z. Hua, Y. Q. Xu, and Z. H. Lu, “Relationship Between Serum HBV DNA Level and HBV-Specific, Nonspecific Cytotoxic T Lymphocytes and Natural Killer Cells in Patients With Chronic Hepatitis B,” Chinese Medical Journal 122, no. 18 (2009): 2129–2132.
CAS PubMed Web of Science® Google Scholar
25G. Galati, A. De Vincentis, U. Vespasiani-Gentilucci, et al., “Coexistence of HBsAg and HBsAb in a Difficult-To-Treat Chronic Hepatitis B: Loss of HBsAg With Entecavir Plus Tenofovir Combination,” BMC Gastroenterology 14 (2014): 94.
10.1186/1471-230X-14-94
PubMed Web of Science® Google Scholar
26M. S. Kwak, G. E. Chung, J. I. Yang, and J. Y. Yim, “Long-Term Outcomes of HBsAg/Anti-HBs Double-Positive Versus HBsAg Single-Positive Patients With Chronic Hepatitis B,” Scientific Reports 9, no. 1 (2019): 19417.
10.1038/s41598-019-56015-8
PubMed Google Scholar

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Volume45, Issue4

April 2025

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Incidence and Predictors of HBsAg Loss in Paediatric Patients With Chronic Hepatitis B Undergoing Antiviral Treatment

ABSTRACT

Background and Aims

Methods

Results

Conclusion

Conflicts of Interest

Open Research

Data Availability Statement

References

Citing Literature

References

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Incidence and Predictors of HBsAg Loss in Paediatric Patients With Chronic Hepatitis B Undergoing Antiviral Treatment

ABSTRACT

Background and Aims

Methods

Results

Conclusion

Conflicts of Interest

Open Research

Data Availability Statement

References

Citing Literature

References

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