Retreatment hepatitis B surface antigen clearance prediction model identifies pegylated interferon alpha candidates in chronic hepatitis B

doi:10.3748/wjg.v31.i44.112719

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Nov 28, 2025 (publication date) through Dec 1, 2025

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World Journal of Gastroenterology

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1007-9327

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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

Retrospective Cohort Study

World J Gastroenterol. Nov 28, 2025; 31(44): 112719
Published online Nov 28, 2025. doi: 10.3748/wjg.v31.i44.112719

Retreatment hepatitis B surface antigen clearance prediction model identifies pegylated interferon alpha candidates in chronic hepatitis B

Yan-Chao Fu, Jun Li, Jia-Yin Wang, Yi-Wen Zhang, Fei Yan, Jing Chen, Qin Du, Chao Yang, Jing Liang, Qing Ye, Hui-Ling Xiang

Yan-Chao Fu, Jia-Yin Wang, Chao Yang, Jing Liang, Qing Ye, Hui-Ling Xiang, Department of Gastroenterology and Hepatology, Tianjin University Central Hospital (Tianjin Third Central Hospital), Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Institute of Hepatobiliary Disease, Tianjin 300170, China

Jun Li, Yi-Wen Zhang, Fei Yan, Jing Chen, The Third Central Clinical College of Tianjin Medical University, Tianjin University Central Hospital (Tianjin Third Central Hospital), Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Institute of Hepatobiliary Disease, Tianjin 300170, China

Qin Du, Nankai University Affiliated Third Central Hospital, Tianjin University Central Hospital (Tianjin Third Central Hospital), Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Institute of Hepatobiliary Disease, Tianjin 300170, China

Co-first authors: Yan-Chao Fu and Jun Li.

Author contributions: Fu YC, Li J and Wang JY contributed equally to manuscript drafting, data curation, formal analysis, investigation, and visualization; Zhang YW, Yan F, Chen J, Du Q, Yang C, Liang J and Ye Q participated in manuscript revision, data curation, and investigation; Xiang HL designed the study, acquired funding, supervised the project, and revised the manuscript.

Supported by the Tianjin Health Research Project (Key Project), No. TJWJ2024ZD004; and Tianjin Key Medical Discipline (Specialty) Construction Project, No. TJYXZDXK-034A.

Institutional review board statement: The study protocol was reviewed and approved by the Medical Ethics Committee of Tianjin Third Central Hospital (No. IRB2020-015-01).

Informed consent statement: The requirement for written informed consent was formally waived by the Medical Ethics Committee of Tianjin Third Central Hospital, as this retrospective cohort study used anonymized medical records without additional specimen collection or impact on patient treatment/prognosis, in compliance with the Declaration of Helsinki (1975) and national regulations on real-world data research.

Conflict-of-interest statement: The authors declare that they have no conflict of interest.

STROBE statement: The authors have read the STROBE Statement—a checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-a checklist of items.

Data sharing statement: The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.

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: Hui-Ling Xiang, MD, Doctor, Department of Gastroenterology and Hepatology, Tianjin University Central Hospital (Tianjin Third Central Hospital), Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Institute of Hepatobiliary Disease, No. 83 Jintang Road, Hedong District, Tianjin 300170, China. huilingxiang@163.com

Received: August 5, 2025
Revised: September 14, 2025
Accepted: October 24, 2025
Published online: November 28, 2025
Processing time: 115 Days and 17.6 Hours

Abstract

BACKGROUND

Chronic hepatitis B (CHB) patients rarely achieve functional cure with initial pegylated interferon alpha-2b (Peg-IFNα-2b) therapy. Validated tools to guide retreatment candidates are lacking. We hypothesized that clinical indicators predict hepatitis B surface antigen (HBsAg) clearance during retreatment.

AIM

To develop a prediction model for HBsAg clearance in Peg-IFNα-2b retreatment.

METHODS

In this retrospective cohort study, we enrolled 135 CHB/compensated cirrhosis patients receiving Peg-IFNα-2b retreatment after initial non-clearance at Tianjin University Central Hospital (2017-2025). Predictors were identified through univariate Cox, least absolute shrinkage and selection operator, and multivariate Cox regression. Model performance was assessed via receiver operating characteristic analysis and Harrell’s C-index, with risk stratification by X-tile optimization.

RESULTS

HBsAg clearance rate was 20.74% (28/135). Independent predictors included: Combination nucleos(t)ide analogue (NA) therapy during initial treatment [hazard ratio (HR) = 0.276, 95% confidence interval (CI): 0.092-0.833], baseline HBsAg at retreatment (HR = 0.571, 95%CI: 0.410-0.795), HBsAg decline after initial treatment (HR = 2.050, 95%CI: 1.108-3.793), and treatment interval (HR = 1.013/week, 95%CI: 1.008-1.018). The retreatment HBsAg clearance prediction score (RHCP-S) demonstrated area under the curve of 0.920 (95%CI: 0.863-0.946), sensitivity of 92.3%, specificity of 79.3%. Clearance rates differed significantly: RHCP-S challenge group (≤ 74 points): 3.45%, RHCP-S probable group (74-110 points): 29.63%, RHCP-S dominant group (≥ 110 points): 80.95% (P < 0.001).

CONCLUSION

The overall HBsAg clearance rate with Peg-IFNα-2b retreatment was 20.74% (28/135). The RHCP-S model identifies optimal retreatment candidates (≥ 110 points) with 80.95% clearance probability, associated with the absence of combination NA therapy during initial treatment, greater initial HBsAg decline, longer intervals, and lower retreatment HBsAg.

Keywords: Chronic hepatitis B; Retreatment; Pegylated interferon alpha; Hepatitis B surface antigen clearance; Prediction model

Core Tip: This pioneering study developed the first predictive model (retreatment hepatitis B surface antigen clearance prediction score) for hepatitis B surface antigen clearance during pegylated interferon retreatment in chronic hepatitis B. Analyzing 135 patients, we found that retreatment candidates scoring ≥ 110 points achieved dramatically higher clearance rates (81% vs 3.45% in low-scorers). Key predictors included pegylated interferon monotherapy, substantial initial hepatitis B surface antigen decline, extended treatment intervals, and lower retreatment baseline hepatitis B surface antigen. The model enables precision selection to avoid futile therapy in 97% of non-responders.