Review
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World J Gastroenterol. Mar 14, 2024; 30(10): 1295-1312
Published online Mar 14, 2024. doi: 10.3748/wjg.v30.i10.1295
Overview of the immunological mechanisms in hepatitis B virus reactivation: Implications for disease progression and management strategies
Hui Ma, Qing-Zhu Yan, Jing-Ru Ma, Dong-Fu Li, Jun-Ling Yang
Hui Ma, Jing-Ru Ma, Department of Clinical Laboratory, The Second Hospital of Jilin University, Changchun 130000, Jilin Province, China
Qing-Zhu Yan, Department of Ultrasound Medicine, The Second Hospital of Jilin University, Changchun 130000, Jilin Province, China
Dong-Fu Li, Digestive Diseases Center, Department of Hepatopancreatobiliary Medicine, The Second Hospital of Jilin University, Changchun 130000, Jilin Province, China
Jun-Ling Yang, Department of Respiratory and Critical Care Medicine, The Second Hospital of Jilin University, Changchun 130000, Jilin Province, China
Author contributions: Ma H contributed to supervision, methodology, formal analysis, and writing-original draft; Yan QZ and Ma JR contributed to validation and data curation; Li DF contributed to resources and writing-review and editing; Yang JL contributed to conceptualization, writing-review, and editing; all authors approved the final submitted version of this manuscript.
Conflict-of-interest statement: The authors declare that there is no conflict of interest.
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: Qing-Zhu Yan, MBBS, MD, Associate Professor, Department of Ultrasound Medicine, The Second Hospital of Jilin University. No. 218 Ziqiang Street, Nanguan District, Changchun 130000, Jilin Province, China. yanqingzhu@jlu.edu.cn
Received: November 17, 2023
Peer-review started: November 17, 2023
First decision: December 14, 2023
Revised: December 25, 2023
Accepted: January 24, 2024
Article in press: January 24, 2024
Published online: March 14, 2024
Processing time: 117 Days and 23.5 Hours
Abstract

Hepatitis B virus (HBV) reactivation is a clinically significant challenge in disease management. This review explores the immunological mechanisms underlying HBV reactivation, emphasizing disease progression and management. It delves into host immune responses and reactivation’s delicate balance, spanning innate and adaptive immunity. Viral factors’ disruption of this balance, as are interactions between viral antigens, immune cells, cytokine networks, and immune checkpoint pathways, are examined. Notably, the roles of T cells, natural killer cells, and antigen-presenting cells are discussed, highlighting their influence on disease progression. HBV reactivation’s impact on disease severity, hepatic flares, liver fibrosis progression, and hepatocellular carcinoma is detailed. Management strategies, including anti-viral and immunomodulatory approaches, are critically analyzed. The role of prophylactic anti-viral therapy during immunosuppressive treatments is explored alongside novel immunotherapeutic interventions to restore immune control and prevent reactivation. In conclusion, this comprehensive review furnishes a holistic view of the immunological mechanisms that propel HBV reactivation. With a dedicated focus on understanding its implications for disease progression and the prospects of efficient management strategies, this article contributes significantly to the knowledge base. The more profound insights into the intricate interactions between viral elements and the immune system will inform evidence-based approaches, ultimately enhancing disease management and elevating patient outcomes. The dynamic landscape of management strategies is critically scrutinized, spanning anti-viral and immunomodulatory approaches. The role of prophylactic anti-viral therapy in preventing reactivation during immunosuppressive treatments and the potential of innovative immunotherapeutic interventions to restore immune control and proactively deter reactivation.

Keywords: Hepatitis B virus reactivation; Immunological mechanisms; Disease progression; Management strategies; Immune response

Core Tip: Hepatitis B virus (HBV) reactivation poses a substantial clinical challenge, demanding a nuanced understanding of immunological mechanisms for effective management. This comprehensive review navigates the intricate landscape of HBV reactivation, spotlighting the delicate balance between host immune responses and viral factors. Emphasis is placed on the roles of T cells, natural killer cells, and antigen-presenting cells in disease progression, alongside the repercussions on severity, hepatic flares, liver fibrosis, and hepatocellular carcinoma. Critical analysis of management strategies, spanning anti-viral and immunomodulatory approaches, informs evidence-based practices. Prophylactic anti-viral therapy’s role during immunosuppression and the potential of innovative immunotherapies are explored, contributing significantly to informed disease management and improved patient outcomes.