Chronic hepatitis B virus (HBV) infection is a common cause of liver disease globally, with a disproportionately high burden in South-East Asia. Vaccines and nucleoside or nucleotide drugs are available and reduce both new infection rates and the development of liver disease in HBV-positive persons who adhere to long-term suppressive treatment. Although there is still considerable value in optimizing access to virus-suppressing regimens, the scientific and medical communities have embarked on a concerted journey to identify new antiviral drugs and immune interventions aimed at curing infection. The mechanisms and drug targets being explored are diverse; however, the field universally recognizes the importance of addressing the persistence of episomal covalently closed circular DNA, the existence of integrated HBV DNA in the host genome and the large antigen load, particularly of hepatitis B surface antigen. Another major challenge is to reinvigorate the exhausted immune response within the liver microenvironment. Ultimately, combinations of new drugs will be required to cure infection. Here we critically review the recent literature that describes the rationale for curative therapies and the resulting compounds that are being tested in clinical trials for hepatitis B.
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G.C.F. is an employee of Janssen Pharmaceuticals. A.B. participates in advisory boards/consultancy on hepatitis B virus (HBV) immune therapy for Gilead, Janssen, Vir, Jiangsu Simcere Pharmaceutical and Humabs BioMed; is the scientific founder of Lion TCR Pte. Ltd.; is an advisor for Arbutus, Assembly, Gilead, Janssen, Myr Pharma, Roche, Transgene and Vir Biotech; and has received research grants from Evotec and Roche. F.Z. participates in advisory boards on HBV for AbbVie, Aligos, Gilead, Janssen, Myr Pharma, Spring Bank, Roche, Transgene and Vir Biotech; and has received research grants from Evotec and Roche. J.H. participates in advisory boards/consultancy for AbbVie, Arbutus, Bristol–Myers Squibb, Gilead Sciences, Johnson & Johnson and Roche, and has received grants from Bristol–Myers Squibb and Johnson & Johnson.
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Fanning, G.C., Zoulim, F., Hou, J. et al. Therapeutic strategies for hepatitis B virus infection: towards a cure. Nat Rev Drug Discov 18, 827–844 (2019). https://doi.org/10.1038/s41573-019-0037-0
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