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World J Gastroenterol. Jul 21, 2022; 28(27): 3282-3296
Published online Jul 21, 2022. doi: 10.3748/wjg.v28.i27.3282
Hepatitis B and circadian rhythm of the liver
Ivana Skrlec, Jasminka Talapko
Ivana Skrlec, Department of Biophysics, Biology, and Chemistry, Faculty of Dental Medicine and Health, J. J. Strossmayer University of Osijek, Osijek 31000, Croatia
Jasminka Talapko, Department of Anatomy Histology, Embryology, Pathology Anatomy and Pathology Histology, Faculty of Dental Medicine and Health, Osijek 31000, Croatia
Author contributions: Škrlec I did the majority of the writing and prepared the figures; Talapko J did some writing and prepared the tables; all authors have read and approved the final manuscript.
Conflict-of-interest statement: There are no conflicts of interest to report.
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: Ivana Skrlec, MSc, PhD, Assistant Professor, Department of Biophysics, Biology, and Chemistry, Faculty of Dental Medicine and Health, J. J. Strossmayer University of Osijek, 21 Crkvena, Osijek 31000, Croatia.
Received: January 11, 2022
Peer-review started: January 11, 2022
First decision: March 8, 2022
Revised: March 15, 2022
Accepted: June 13, 2022
Article in press: June 13, 2022
Published online: July 21, 2022

The circadian rhythm in humans is determined by the central clock located in the hypothalamus’s suprachiasmatic nucleus, and it synchronizes the peripheral clocks in other tissues. Circadian clock genes and clock-controlled genes exist in almost all cell types. They have an essential role in many physiological processes, including lipid metabolism in the liver, regulation of the immune system, and the severity of infections. In addition, circadian rhythm genes can stimulate the immune response of host cells to virus infection. Hepatitis B virus (HBV) infection is the leading cause of liver disease and liver cancer globally. HBV infection depends on the host cell, and hepatocyte circadian rhythm genes are associated with HBV replication, survival, and spread. The core circadian rhythm proteins, REV-ERB and brain and muscle ARNTL-like protein 1, have a crucial role in HBV replication in hepatocytes. In addition to influencing the virus’s life cycle, the circadian rhythm also affects the pharmacokinetics and efficacy of antiviral vaccines. Therefore, it is vital to apply antiviral therapy at the appropriate time of day to reduce toxicity and improve the effectiveness of antiviral treatment. For these reasons, understanding the role of the circadian rhythm in the regulation of HBV infection and host responses to the virus provides us with a new perspective of the interplay of the circadian rhythm and anti-HBV therapy. Therefore, this review emphasizes the importance of the circadian rhythm in HBV infection and the optimization of antiviral treatment based on the circadian rhythm-dependent immune response.

Keywords: Circadian rhythm, Clock genes, Hepatitis B virus, Immune system, Liver

Core Tip: Some studies in the literature contribute to the association of the circadian rhythm and liver pathophysiology associated with hepatitis B virus (HBV) infection. However, this is the first review to report the latest molecular mechanisms of HBV infection, including cellular circadian rhythm disorders, circadian clock-related immune response, therapeutic strategies in improving health outcomes, and the significance of personalized medicine and chronotherapy in treating chronic HBV infections.