Hepatitis B and circadian rhythm of the liver

Abstract

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.

The contribution of circadian clock to the biological processes

“…Studies have shown that an increasing number of diagnosed cases of hepatocellular carcinoma are thought to be related to circadian clock disorders, obesity and non-alcoholic fatty liver disease ( Crespo et al, 2021 ). The occurrence and progression of liver cancer relies on multiple molecular mechanisms, involving genetic and epigenetic alterations of oncogenes and tumor suppressor genes, as well as disorder control, abnormal functions and inappropriate interactions of key molecular cascades such as Hedgehog, MAPK and PI3K/AKT/mTOR signaling pathways ( Skrlec and Talapko, 2022 ). Studies have reported that decreased levels of melatonin or decreased excretion of its main metabolite, 6-thiooxidative melatonin, are associated with an increased risk of cancer, suggesting the anticancer effects of this indoleamine.…”

Circadian control of ConA-induced acute liver injury and inflammatory response via Bmal1 regulation of Junb

“…Among the core clock components, REV-ERB regulates HBV and HDV particle entry, and Bmal1 directly binds to HBV DNA, increasing the activity of the HBV promoter activity and thus promoting the production of viral particles in the liver. 12 , 13 On the contrary, Bmal1 depletion inhibits the replication of the HCV via disturbing the lipid signalling pathways. 14 …”