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©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
Recurrence and influencing factors of hepatitis B surface antigen seroclearance induced by peginterferon alpha-based regimens
Rui Lu, Meng Zhang, Zi-Han Liu, Miao Hao, Yan Tian, Mei Li, Feng-Ping Wu, Wen-Jun Wang, Juan-Juan Shi, Xin Zhang, Xiao-Li Jia, Zi-Cheng Jiang, Xue-Mei Li, Guang-Hua Xu, Ya-Ping Li, Shuang-Suo Dang
Rui Lu, Meng Zhang, Zi-Han Liu, Miao Hao, Yan Tian, Mei Li, Feng-Ping Wu, Wen-Jun Wang, Juan-Juan Shi, Xin Zhang, Xiao-Li Jia, Ya-Ping Li, Shuang-Suo Dang, Department of Infectious Diseases, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710004, Shaanxi Province, China
Zi-Cheng Jiang, Xue-Mei Li, Department of Infectious Diseases, Ankang Central Hospital, Ankang 725000, Shaanxi Province, China
Guang-Hua Xu, Department of Infectious Diseases, The Affiliated Hospital of Yan’an University, Yan’an 716000, Shaanxi Province, China
Co-first authors: Rui Lu and Meng Zhang.
Co-corresponding authors: Ya-Ping Li and Shuang-Suo Dang.
Author contributions: Lu R, Dang SS and Li YP conceptualized and designed the research. Li YP, Dang SS, Wu FP, Li M, Shi JJ, Wang WJ, Zhang X, and Jia XL were responsible for the enrollment and follow-up of the observed subjects. Tian Y, Liu ZH, Hao M and Zhang M were responsible for collecting the data. Jiang ZC, Li XM and Xu GH contributed to collecting a portion of the data. Lu R performed the analysis with assistance from Wu FP and Li YP. Both Dang SS and Li YP have played important and indispensable roles in the experimental design, data interpretation and manuscript preparation as the co-corresponding authors. Dang SS and Li YP applied for and obtained the funds for this research project. Dang SS conceptualized, designed, supervised the whole process of the project, and was responsible for submission of the current version of the manuscript. Li YP was instrumental and responsible for data re-analysis and re-interpretation, figure re-plotting, comprehensive literature search, and preparation of the current version of the manuscript. This collaboration between Li YP and Dang SS is crucial for the publication of this manuscript. All authors contributed to the article and approved the submitted version.
Supported by National Key Research and Development Program of China, No. 2023YFC2308105.
Institutional review board statement: The study was reviewed and approved by the Medical Ethics Committee of the Second Affiliated Hospital of the Xi'an Jiaotong University (Approval No. 2018033).
Informed consent statement: All study participants, or their legal guardian, provided informed written consent prior to study enrollment.
Conflict-of-interest statement: The authors have no relevant financial or non-financial interests to disclose.
Data sharing statement: No additional data are available.
STROBE statement: The authors have read the STROBE Statement—checklist of items, and the manuscript was prepared and revised according to the STROBE Statement—checklist of items.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
https://creativecommons.org/Licenses/by-nc/4.0/ Corresponding author: Shuang-Suo Dang, PhD, Professor, Department of Infectious Diseases, The Second Affiliated Hospital of Xi’an Jiaotong University, No. 157 Xiwu Road, Xi’an 710004, Shaanxi Province, China.
dang212@126.com
Received: August 21, 2024
Revised: September 27, 2024
Accepted: October 28, 2024
Published online: November 28, 2024
Processing time: 83 Days and 21.7 Hours
BACKGROUND
The long-term stability of hepatitis B surface antigen (HBsAg) seroclearance following peginterferon alpha (peg-IFN-α)-based therapy has not been extensively studied, leaving the full potential and limitations of this strategy unclear.
AIM
To assess HBsAg recurrence after seroclearance achieved by peg-IFN-α regimens.
METHODS
This prospective, multicenter, observational study was conducted from November 2015 to June 2021 at three Chinese hospitals: The Second Affiliated Hospital of Xi’an Jiaotong University, Ankang Central Hospital, and The Affiliated Hospital of Yan’an University. Participants who achieved HBsAg seroclearance following peg-IFN-α-based treatments were monitored every 4-12 weeks post-treatment for hepatitis B virus (HBV) markers, HBV DNA, and liver function. The primary outcome was HBV recurrence, defined as the reemergence of HBsAg, HBV DNA, or both, at least twice within 4-8 weeks of follow-up.
RESULTS
In total, 121 patients who achieved HBsAg seroclearance were enrolled. After a median follow-up of 84.0 (48.0, 132.0) weeks, four subjects were lost to follow-up. HBsAg recurrence was detected in 16 patients. The cumulative HBsAg recurrence rate in the intention-to-treat population was 15.2%. Multivariate logistic regression analysis demonstrated that consolidation time < 12 weeks [odds ratio (OR) = 28.044, 95%CI: 4.525-173.791] and hepatitis B surface antibody disappearance during follow-up (OR = 46.445, 95%CI: 2.571-838.957) were strong predictors of HBsAg recurrence. HBV DNA positivity and decompensation of liver cirrhosis and hepatocellular carcinoma were not observed.
CONCLUSION
HBsAg seroclearance following peg-IFN-α treatment was durable over 84 weeks of follow-up with a cumulative recurrence rate of 15.2%.
Core Tip: Hepatitis B surface antigen seroclearance is an ideal target for peginterferon alpha (peg-IFN-α) treatment in patients with chronic hepatitis B and a focus of global research. However, there is limited information about the duration of seroclearance after peg-IFN-α withdrawal. This study examined follow-up observational data after peg-IFN-α withdrawal among patients who achieved functional cure at three centers. The longest follow-up duration was 252 weeks, representing one of the longest follow-up times currently available. We believe that this study offers valuable guidance and reference for the clinical use of peg-IFN-α, including the optimal timing of treatment cessation and the importance of continuous and standardized follow-up after treatment.
