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Novel Therapy for Functional Cure of Chronic Hepatitis B Virus Infection

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Hepatitis B Virus and Liver Disease

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Abstract

Functional cure is the currently preferable and optimal treatment endpoint, which refers to sustained seroclearance of HBsAg with or without seroconversion of antibody to HBsAg. Functional cure is associated with improved clinical outcomes. The unsatisfactorily low rate of functional cure achieved by currently approved therapies [i.e., nucleos(t)ide reverse transcriptase inhibitor (NRTI) or pegylated interferon] triggers the ongoing search for new treatment approaches. Cessation of long-term NRTI aiming at subsequent functional cure has led to heterogeneous results in patients with different baseline characteristics. Meticulous patient selection is required with efforts to identify patients with favorable factors including Caucasian ethnicity and low HBsAg level. For novel agents, reduction of viral burden and enhancement/restoration of host immunity are equally important. Most agents currently in clinical phase of development demonstrated favorable results in suppression of viral proteins and genomic materials, and some agents will enter phase 3 clinical trials for further evaluation. Safety data is of paramount importance. The future treatment regime will likely entail a combination of NRTI, virus-directing agent, and immune boosting agent. The best cocktail therapy is still unknown, and will need to be revealed by well-designed randomized controlled trials.

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  1. Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Pok Fu Lam, Hong Kong

    Lung-Yi Mak & Man-Fung Yuen

  2. State Key Laboratory of Liver Research, The University of Hong Kong, Pok Fu Lam, Hong Kong

    Lung-Yi Mak & Man-Fung Yuen

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  1. Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan

    Jia-Horng Kao

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MF Yuen serves as advisor/consultant for AbbVie, Assembly Biosciences, Aligos Therapeutics, Arbutus Biopharma, Bristol Myer Squibb, Clear B Therapeutics, Dicerna Pharmaceuticals, Finch Therapeutics, GlaxoSmithKline, Gilead Sciences, Immunocore, Janssen, Merck Sharp and Dohme, Hoffmann-La Roche and Springbank Pharmaceuticals, Vir Biotechnology and receives grant/research support from Assembly Biosciences, Aligos Therapeutics, Arrowhead Pharmaceuticals, Bristol Myer Squibb, Fujirebio Incorporation, Gilead Sciences, Immunocore, Merck Sharp and Dohme, Hoffmann-La Roche, Springbank Pharmaceuticals and Sysmex Corporation.LY Mak has nothing to disclose.

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Mak, LY., Yuen, MF. (2021). Novel Therapy for Functional Cure of Chronic Hepatitis B Virus Infection. In: Kao, JH. (eds) Hepatitis B Virus and Liver Disease. Springer, Singapore. https://doi.org/10.1007/978-981-16-3615-8_19

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