Ye XY, He XZ, Hu ZT, Zheng FF, Huang XG, Xie XM, Chen FH, Ou HB, Qiu RX. Integrated transcriptomics and metabolomics reveal neutrophil extracellular trap associated with interferon treatment for chronic hepatitis B. World J Hepatol 2026; 18(4): 114804 [DOI: 10.4254/wjh.v18.i4.114804]
Corresponding Author of This Article
Rong-Xian Qiu, Department of Infectious Diseases, The Affiliated Hospital of Putian University, No. 181 Meiyuan East Road, Putian 351100, Fujian Province, China. 18850959988@163.com
Research Domain of This Article
Gastroenterology & Hepatology
Article-Type of This Article
Basic Study
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This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (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: http://creativecommons.org/licenses/by-nc/4.0/
Apr 27, 2026 (publication date) through Apr 22, 2026
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Journal Information of This Article
Publication Name
World Journal of Hepatology
ISSN
1948-5182
Publisher of This Article
Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA
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Ye XY, He XZ, Hu ZT, Zheng FF, Huang XG, Xie XM, Chen FH, Ou HB, Qiu RX. Integrated transcriptomics and metabolomics reveal neutrophil extracellular trap associated with interferon treatment for chronic hepatitis B. World J Hepatol 2026; 18(4): 114804 [DOI: 10.4254/wjh.v18.i4.114804]
Xiang-Yang Ye, Xiong-Zhi He, Zhen-Ting Hu, Feng-Feng Zheng, Xiao-Gang Huang, Xue-Mei Xie, Fei-Hua Chen, Han-Bing Ou, Rong-Xian Qiu, Department of Infectious Diseases, The Affiliated Hospital of Putian University, Putian 351100, Fujian Province, China
Xiang-Yang Ye, Department of Clinic Medicine, Fujian Medical University, Fuzhou 350122, Fujian Province, China
Author contributions: Ye XY, Ou HB, and Qiu RX designed experiments, data analyses, and wrote the manuscript; Ye XY, He XZ, and Hu ZT performed experiments and collected data; Zheng FF, Huang XG, Xie XM, and Chen FH provided technical support and collected data; and all authors have reviewed the manuscript.
Institutional review board statement: This work was approved by the Human Research Ethics Committee in the Affiliated Hospital of Putian University (No. PYFL202416).
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: Datasets are hosted in public repositories Science data bank under accession number 26078 and are available at the following URL: https://doi.org/10.57760/sciencedb.26078.
Corresponding author: Rong-Xian Qiu, Department of Infectious Diseases, The Affiliated Hospital of Putian University, No. 181 Meiyuan East Road, Putian 351100, Fujian Province, China. 18850959988@163.com
Received: September 29, 2025 Revised: November 11, 2025 Accepted: January 9, 2026 Published online: April 27, 2026 Processing time: 205 Days and 4.9 Hours
Abstract
BACKGROUND
Chronic hepatitis B (CHB) is a significant global health issue, and interferon (IFN) is one of the main first-line therapies for CHB.
AIM
To investigate the altered transcriptome, metabolites, and their correlations, as well as the effects and mechanisms of IFN treatment for CHB.
METHODS
The patients received peginterferon alfa-2b at a dose of 180 μg for 0, 1, 3, and 6 months and serum samples were collected for clinical biological assays, transcriptomics, and metabolomics analyses.
RESULTS
The results showed that IFN-related immune pathways and neutrophil extracellular traps (NETs) were the most significantly altered pathways following IFN treatment. Correlation analysis revealed a strong link between immune system-related genes in the transcriptome and dipeptides in the metabolome during IFN-α treatment. Notably, core components of NETs, including histones H2A clustered histone 14, H2B clustered histone 5, H3 clustered histone 1, and H4 clustered histone 4, were significantly increased after IFN treatment. The positively charged histones may bind to the negatively charged viral envelope, potentially enhancing the antiviral effect.
CONCLUSION
Integrated non-targeted transcriptomic and metabolomic analyses to CHB patients undergoing IFN-α treatment revealed that IFN-related immune pathways and NETs were the most significantly affected pathways during IFN treatment. These findings provide a deeper understanding of the role of NETs and dipeptides in the antiviral response to IFN treatment for CHB.
Core Tip: Chronic hepatitis B is a significant global health issue, and interferon (IFN) is one of the main first-line therapies for chronic hepatitis B. Non-targeted transcriptomic and metabolomic analyses revealed that IFN-related immune pathways and neutrophil extracellular trap formation were the most significantly altered pathways after IFN treatment. Core components of neutrophil extracellular traps including histones were notably increased and potentially enhance the antiviral response.
