Salama II, Sami SM, Salama SI, Abdel-Latif GA, Shaaban FA, Fouad WA, Abdelmohsen AM, Raslan HM. Current and novel modalities for management of chronic hepatitis B infection. World J Hepatol 2023; 15(5): 585-608 [PMID: 37305370 DOI: 10.4254/wjh.v15.i5.585]
Corresponding Author of This Article
Iman Ibrahim Salama, MD, Academic Research, Research Scientist, Department of Community Medicine Research, National Research Centre, El bouhoth street, Giza 12411, Dokki, Egypt. salamaiman@yahoo.com
Research Domain of This Article
Gastroenterology & Hepatology
Article-Type of This Article
Review
Open-Access Policy of This Article
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/
World J Hepatol. May 27, 2023; 15(5): 585-608 Published online May 27, 2023. doi: 10.4254/wjh.v15.i5.585
Current and novel modalities for management of chronic hepatitis B infection
Iman Ibrahim Salama, Samia M Sami, Somaia I Salama, Ghada A Abdel-Latif, Fatma A Shaaban, Walaa A Fouad, Aida M Abdelmohsen, Hala M Raslan
Iman Ibrahim Salama, Somaia I Salama, Ghada A Abdel-Latif, Walaa A Fouad, Aida M Abdelmohsen, Department of Community Medicine Research, National Research Centre, Giza 12411, Dokki, Egypt
Samia M Sami, Fatma A Shaaban, Department of Child Health, National Research Centre, Giza 12411, Dokki, Egypt
Hala M Raslan, Department of Internal Medicine, National Research Centre, Giza 12411, Dokki, Egypt
Author contributions: Salama II designed the review and implementation; Salama II, Salama SI, Abdel-Latif GA, and Raslan HA were responsible for writing the manuscript; Sami SM, Shaaban FA, Abdelmohsen AM, and Fouad WA were responsible for the first review; and all authors reviewed and approved the manuscript.
Conflict-of-interest statement: All authors report having 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: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Iman Ibrahim Salama, MD, Academic Research, Research Scientist, Department of Community Medicine Research, National Research Centre, El bouhoth street, Giza 12411, Dokki, Egypt. salamaiman@yahoo.com
Received: November 19, 2022 Peer-review started: November 19, 2022 First decision: February 1, 2023 Revised: March 13, 2023 Accepted: April 12, 2023 Article in press: April 12, 2023 Published online: May 27, 2023
Abstract
Over 296 million people are estimated to have chronic hepatitis B viral infection (CHB), and it poses unique challenges for elimination. CHB is the result of hepatitis B virus (HBV)-specific immune tolerance and the presence of covalently closed circular DNA as mini chromosome inside the nucleus and the integrated HBV. Serum hepatitis B core-related antigen is the best surrogate marker for intrahepatic covalently closed circular DNA. Functional HBV “cure” is the durable loss of hepatitis B surface antigen (HBsAg), with or without HBsAg seroconversion and undetectable serum HBV DNA after completing a course of treatment. The currently approved therapies are nucleos(t)ide analogues, interferon-alpha, and pegylated-interferon. With these therapies, functional cure can be achieved in < 10% of CHB patients. Any variation to HBV or the host immune system that disrupts the interaction between them can lead to reactivation of HBV. Novel therapies may allow efficient control of CHB. They include direct acting antivirals and immunomodulators. Reduction of the viral antigen load is a crucial factor for success of immune-based therapies. Immunomodulatory therapy may lead to modulation of the host immune system. It may enhance/restore innate immunity against HBV (as toll-like-receptors and cytosolic retinoic acid inducible gene I agonist). Others may induce adaptive immunity as checkpoint inhibitors, therapeutic HBV vaccines including protein (HBsAg/preS and hepatitis B core antigen), monoclonal or bispecific antibodies and genetically engineered T cells to generate chimeric antigen receptor-T or T-cell receptor-T cells and HBV-specific T cells to restore T cell function to efficiently clear HBV. Combined therapy may successfully overcome immune tolerance and lead to HBV control and cure. Immunotherapeutic approaches carry the risk of overshooting immune responses causing uncontrolled liver damage. The safety of any new curative therapies should be measured in relation to the excellent safety of currently approved nucleos(t)ide analogues. Development of novel antiviral and immune modulatory therapies should be associated with new diagnostic assays used to evaluate the effectiveness or to predict response.
Core Tip: Chronic hepatitis B virus (HBV) infection is a result of immune tolerance and the presence of covalently closed circular DNA and the integrated HBV. The currently approved therapies are nucleos(t)ide analogues, interferon-alpha, and pegylated-interferon-alpha, with functional cure achieved in < 10% of patients. Disruption of the interaction between HBV or the host immune system can lead to HBV reactivation. Novel therapies include direct acting antivirals and immunomodulators. Immunomodulators may enhance/restore innate and adaptive immunity against HBV (as toll-like-receptors and retinoic acid inducible gene-1 agonist), checkpoint inhibitors, therapeutic HBV vaccines, and genetically engineered T cells to restore T cell function.
