Tian B, Tian C, Shen CL, Zhang Q. From virological selection to immune stratification: Hepatitis B virus-specific T cells for precision pegylated interferon therapy in chronic hepatitis B. World J Hepatol 2026; 18(9): 124884 [DOI: 10.4254/wjh.124884]
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Tian B, Tian C, Shen CL, Zhang Q. From virological selection to immune stratification: Hepatitis B virus-specific T cells for precision pegylated interferon therapy in chronic hepatitis B. World J Hepatol 2026; 18(9): 124884 [DOI: 10.4254/wjh.124884]
World J Hepatol. Sep 27, 2026; 18(9): 124884 Published online Sep 27, 2026. doi: 10.4254/wjh.124884
From virological selection to immune stratification: Hepatitis B virus-specific T cells for precision pegylated interferon therapy in chronic hepatitis B
Bing Tian, Chen Tian, Chuan-Lai Shen, Qun Zhang
Bing Tian, Chen Tian, Qun Zhang, Department of Infectious Diseases, Zhongda Hospital, Southeast University, Nanjing 210009, Jiangsu Province, China
Bing Tian, Department of Infectious Diseases, Zhongda Hospital, Southeast University (Jiangbei, Nanjing Dachang Hospital), Nanjing 211500, Jiangsu Province, China
Chuan-Lai Shen, Department of Microbiology and Immunology, Southeast University Medical School, Nanjing 210009, Jiangsu Province, China
Co-first authors: Bing Tian and Chen Tian.
Author contributions: All four authors made equal substantial contributions to this review article; Zhang Q conceptualized the review framework, supervised the entire study, and made critical revisions to the manuscript; Tian B carried out literature retrieval, synthesized research evidence, and drafted the original manuscript; Tian B, Tian C, Shen CL, and Zhang Q reviewed and revised the manuscript and approved the final version for submission; Tian B and Tian C have made crucial and indispensable contributions towards the completion of the project and thus qualified as the co-first authors of the paper.
AI contribution statement: The authors used Grammarly to assist with language editing and refinement. All scientific content was critically reviewed and verified by the authors, who take full responsibility for the final manuscript.
Supported by Jiangsu Province High-Level Hospital Construction Funds of Zhongda Hospital, School of Medicine, Southeast University, No. 2024GSPKY23; and Chinese Foundation for Hepatitis Prevention and Control Muxin research fund of CHB, No. MX202413.
Conflict-of-interest statement: All authors have no conflicts of interest to declare.
Received: July 1, 2026 Revised: July 31, 2026 Accepted: August 14, 2026 Published online: September 27, 2026 Processing time: 84 Days and 0.5 Hours
Abstract
Pegylated interferon (PEG-IFN) alpha, an important agent for chronic hepatitis B (CHB), exerts antiviral and immunomodulatory activities and serves as a core therapy to pursue functional cure. However, there are significant individual differences in treatment response, and the lack of reliable patient-selection strategies remains a major limitation to clinical application. Recent studies have shown that hepatitis B virus (HBV)-specific T cells are the core effector cells mediating viral clearance and maintaining immune control, and that the degree of their functional restoration is closely related to responses to PEG-IFN treatment and hepatitis B surface antigen clearance. In chronic HBV infection, HBV-specific T cells generally exhibit characteristics such as reduced numbers, functional exhaustion, metabolic abnormalities, and epigenetic remodeling. PEG-IFN can achieve immune remodeling by enhancing HBV-specific T cell responses, promoting the formation of memory-like T cells, improving multifunctional effector functions, and partially reversing the exhausted state. This review summarizes HBV-specific T cell dysfunction in chronic HBV infection, PEG-IFN-mediated immune remodeling mechanisms and relevant biomarker advances, to discuss the value of these T cells for precise interferon candidate screening and immune-stratified therapy. Such indicators may transform CHB management from virology-based to immunology-guided strategies and support precision treatment toward functional cure.
Core Tip: Currently, patient selection for pegylated interferon (PEG-IFN) therapy predominantly relies on virological markers, which fail to fully recapitulate host immune competence. This review highlights that hepatitis B virus-specific T cells constitute core immune biomarkers predictive of treatment response and functional cure. Synthesizing available evidence concerning T cell exhaustion, regenerative potential, effector function and comprehensive immune profiling, we propose that future patient selection algorithms should transition from virology-only criteria toward immune stratification strategies. This conceptual framework underpins the development of precision PEG-IFN therapy for chronic hepatitis B.
