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World J Clin Cases. Jun 16, 2022; 10(17): 5518-5530
Published online Jun 16, 2022. doi: 10.12998/wjcc.v10.i17.5518
Occult hepatitis B — the result of the host immune response interaction with different genomic expressions of the virus
George Sebastian Gherlan
George Sebastian Gherlan, Department of Infectious Diseases, “Carol Davila” University of Medicine and Pharmacy, Bucharest 030303, Romania
George Sebastian Gherlan, Department of Infectious Diseases, “Dr. Victor Babes” Hospital of Infectious and Tropical Diseases, Bucharest 030303, Romania
Author contributions: Gherlan GS reviewed the literature, wrote the paper and elaborated the figures.
Conflict-of-interest statement: Gherlan GS has no conflict of interest to declare.
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: George Sebastian Gherlan, MD, PhD, Lecturer, Department of Infectious Diseases, “Carol Davila” University of Medicine and Pharmacy, 281 Mihai Bravu Street, Bucharest 030303, Romania. george.gherlan@umfcd.ro
Received: January 5, 2022
Peer-review started: January 5, 2022
First decision: January 27, 2022
Revised: January 30, 2022
Accepted: April 4, 2022
Article in press: April 4, 2022
Published online: June 16, 2022
Processing time: 154 Days and 23.4 Hours
Abstract

With over 40 years of history, occult hepatitis B infection (OBI) continues to remain an important and challenging public health problem. Defined as the presence of replication-competent hepatitis B virus (HBV) DNA (i.e., episomal HBV covalently closed circular DNA) in the liver and/or HBV DNA in the blood of people who test negative for hepatitis B surface antigen (HBsAg) in currently available assays, OBI is currently diagnosed using polymerase chain reaction (PCR) and real-time PCR assays. However, all efforts should be made to exclude a false negative HBsAg in order to completely follow the definition of OBI. In recent years, significant advances have been made in understanding the HBV lifecycle and the molecular mechanisms that lead to the persistence of the virus in the occult form. These factors are mainly related to the host immune system and, to a smaller proportion, to the virus. Both innate and adaptive immune responses are important in HBV infection management, and epigenetic changes driven by host mechanisms (acetylation, methylation, and microRNA implication) are added to such actions. Although greater genetic variability in the S gene of HBV isolated from OBIs was found compared with overt infection, the mechanisms of OBI are not mainly viral mutations.

Keywords: Hepatitis B virus; Occult hepatitis B; Covalently closed circular DNA; Epigenetic factors; Immune factors; MicroRNA

Core Tip: Every year, our knowledge of occult hepatitis B infection becomes richer with new information. This review is an up-to-date analysis of the viral and host factors that interact and lead to an occult form of hepatitis B virus infection. The latest discoveries in microRNA involvement, epigenetic mechanisms, immune system factors, and viral variants have been included for a comprehensive understanding of this challenging problem. We emphasize that occult hepatitis B infection is not only and not primarily a virus-driven condition; host immune and epigenetic mechanisms are also its important determinants.