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World J Gastroenterol. Oct 28, 2022; 28(40): 5784-5800
Published online Oct 28, 2022. doi: 10.3748/wjg.v28.i40.5784
Heterogeneity of immune control in chronic hepatitis B virus infection: Clinical implications on immunity with interferon-α treatment and retreatment
Guo-Qing Yin, Ke-Ping Chen, Xiao-Chun Gu
Guo-Qing Yin, Ke-Ping Chen, Xiao-Chun Gu, Center of Hepatology, Zhong-Da Hospital, Southeast University, Nanjing 210009, Jiangsu Province, China
Author contributions: All authors contributed to the study conception and design; The first draft of the manuscript was written by Yin GQ; All authors commented on previous versions of the manuscript, they all read and approved the final manuscript.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
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:
Corresponding author: Guo-Qing Yin, MD, PhD, Chief Doctor, Chief Physician, Center of Hepatology, Zhong-Da Hospital, Southeast University, No. 87 Dingjiaqiao, Nanjing 210009, Jiangsu Province, China.
Received: May 10, 2022
Peer-review started: May 10, 2022
First decision: August 20, 2022
Revised: September 8, 2022
Accepted: October 9, 2022
Article in press: October 9, 2022
Published online: October 28, 2022

Hepatitis B virus (HBV) infection is a global public health issue. Interferon-α (IFN-α) treatment has been used to treat hepatitis B for over 20 years, but fewer than 5% of Asians receiving IFN-α treatment achieve functional cure. Thus, IFN-α retreatment has been introduced to enhance antiviral function. In recent years, immune-related studies have found that the complex interactions between immune cells and cytokines could modulate immune response networks, in-cluding both innate and adaptive immunity, triggering immune responses that control HBV replication. However, heterogeneity of the immune system to control HBV infection, particularly HBV-specific CD8+ T cell heterogeneity, has consequ-ential effects on T cell-based immunotherapy for treating HBV infection. Altogether, the host’s genetic variants, negative-feedback regulators and HBV components affecting the immune system's ability to control HBV. In this study, we reviewed the literature on potential immune mechanisms affecting the immune control of HBV and the clinical effects of IFN-α treatment and retreatment.

Keywords: Hepatitis B virus, Chronic, Functional cure, Heterogeneity, Immunity, Immune control, Interferon-α, Retreatment

Core Tip: Hepatitis B virus (HBV)-specific immune control is characterized by distinct phenotypical and functional profiles. Owing to the negative feedback associated with all immune responses in an infected host, immunomodulators regulating a single immune pathway are unlikely to fully restore antiviral immunity. Interferon-α (IFN-α) treatment was shown to simultaneously affect multiple immune pathways and various immune cell populations in the host and integrate signals toward improving HBV-specific immune control. In addition, IFN-α retreatment was shown to improved functional cure rates, indicating that could gradually enhance the overall immune control.