Scientific and medical evidence informing expansion of hepatitis B treatment guidelines

Affiliations

¹ Immunobiology, Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK. Electronic address: p.kennedy@qmul.ac.uk.
² Medical Clinic and Polyclinic, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; German Center for Infection Research, Hamburg-Lübeck-Borstel-Riems Site, Hamburg, Germany.
³ Programme in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore.
⁴ Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, Germany; German Center for Infection Research, Partner Site Hannover-Braunschweig, Hannover, Germany; Centre for Individualised Infection Medicine, Hannover, Germany; Cluster of Excellence RESIST, Hannover, Germany.
⁵ Schwartz Reisman Liver Research Centre, Toronto General Hospital Research Institute, University Health Network, Toronto, ON, Canada; Toronto Centre for Liver Disease, Toronto General Hospital Research Institute, University Health Network, Toronto, ON, Canada; Department of Immunology, University of Toronto, Toronto, ON, Canada.
⁶ Division of Immunology, Transplantation, and Infectious Diseases, IRCCS San Raffaele Scientific Institute, Milan, Italy; Vita-Salute San Raffaele University, Milan, Italy.
⁷ Institute of Virology, Technical University of Munich/Helmholtz Center Munich, Munich, Germany; German Center for Infectious Research, Munich Partner Site, Munich, Germany.
⁸ Department of Metabolism Digestion and Reproduction-Liver Unit, St Mary's Hospital, London, UK.
⁹ INSERM U1052, CNRS UMR-5286, Cancer Research Center of Lyon, Lyon, France; University of Lyon, UMR_S1052, Cancer Research Center of Lyon, Lyon, France; The Lyon Hepatology Institute EVEREST, Lyon, France; Department of Hepatology, Croix Rousse Hospital, Hospices Civils de Lyon, Lyon, France; Department of Internal Medicine, Sapienza University, Rome, Italy; IIT Center for Life Nanoscience, Sapienza University, Rome, Italy.
¹⁰ Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Division of Gastroenterology and Hepatology, National University Health System, Singapore.
¹¹ Department of Molecular Microbiology and Immunology, Saint Louis University School of Medicine, Saint Louis, MO, USA; Institute for Drug and Biotherapeutic Development, Saint Louis University, Saint Louis, MO, USA.
¹² Université Claude-Bernard Lyon 1, INSERM, UMR 1350 PaThLiv, Lyon, France; The Lyon Hepatology Institute, IHU EVEREST, Lyon, France.
¹³ Westmead Institute for Medical Research, University of Sydney School of Medicine and Health, Sydney, NSW, Australia.

PMID: 40714040
DOI: 10.1016/S2468-1253(25)00053-6

Review

Scientific and medical evidence informing expansion of hepatitis B treatment guidelines

Patrick T Kennedy et al. Lancet Gastroenterol Hepatol. 2025 Oct.

. 2025 Oct;10(10):941-951.

doi: 10.1016/S2468-1253(25)00053-6. Epub 2025 Jul 23.

Affiliations

¹ Immunobiology, Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK. Electronic address: p.kennedy@qmul.ac.uk.
² Medical Clinic and Polyclinic, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; German Center for Infection Research, Hamburg-Lübeck-Borstel-Riems Site, Hamburg, Germany.
³ Programme in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore.
⁴ Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, Germany; German Center for Infection Research, Partner Site Hannover-Braunschweig, Hannover, Germany; Centre for Individualised Infection Medicine, Hannover, Germany; Cluster of Excellence RESIST, Hannover, Germany.
⁵ Schwartz Reisman Liver Research Centre, Toronto General Hospital Research Institute, University Health Network, Toronto, ON, Canada; Toronto Centre for Liver Disease, Toronto General Hospital Research Institute, University Health Network, Toronto, ON, Canada; Department of Immunology, University of Toronto, Toronto, ON, Canada.
⁶ Division of Immunology, Transplantation, and Infectious Diseases, IRCCS San Raffaele Scientific Institute, Milan, Italy; Vita-Salute San Raffaele University, Milan, Italy.
⁷ Institute of Virology, Technical University of Munich/Helmholtz Center Munich, Munich, Germany; German Center for Infectious Research, Munich Partner Site, Munich, Germany.
⁸ Department of Metabolism Digestion and Reproduction-Liver Unit, St Mary's Hospital, London, UK.
⁹ INSERM U1052, CNRS UMR-5286, Cancer Research Center of Lyon, Lyon, France; University of Lyon, UMR_S1052, Cancer Research Center of Lyon, Lyon, France; The Lyon Hepatology Institute EVEREST, Lyon, France; Department of Hepatology, Croix Rousse Hospital, Hospices Civils de Lyon, Lyon, France; Department of Internal Medicine, Sapienza University, Rome, Italy; IIT Center for Life Nanoscience, Sapienza University, Rome, Italy.
¹⁰ Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Division of Gastroenterology and Hepatology, National University Health System, Singapore.
¹¹ Department of Molecular Microbiology and Immunology, Saint Louis University School of Medicine, Saint Louis, MO, USA; Institute for Drug and Biotherapeutic Development, Saint Louis University, Saint Louis, MO, USA.
¹² Université Claude-Bernard Lyon 1, INSERM, UMR 1350 PaThLiv, Lyon, France; The Lyon Hepatology Institute, IHU EVEREST, Lyon, France.
¹³ Westmead Institute for Medical Research, University of Sydney School of Medicine and Health, Sydney, NSW, Australia.

PMID: 40714040
DOI: 10.1016/S2468-1253(25)00053-6

Abstract

Chronic hepatitis B treatment relies on nucleoside or nucleotide analogue drugs that suppress hepatitis B virus (HBV) replication, normalise liver enzymes, and slow disease progression with excellent safety profiles. Treatment is not curative, and patients remain at risk of cirrhosis and hepatocellular carcinoma. Treatment guidelines have generally restricted antiviral therapy to individuals with high HBV DNA and elevated ALT or hepatic fibrosis, often requiring longitudinal testing that can be scarcely available in resource-limited settings. Consequently, fewer than 3% of people living with HBV infection are receiving antiviral therapy. Guidelines from China and WHO recently broadened access criteria to antiviral therapy, but there are people who fall outside these guidelines who could still benefit from treatment initiation. The pathological processes induced by HBV infection are still active in these patients. We present the benefits and risks of expanding treatment eligibility. We believe that the benefits of reduced hepatic damage and carcinogenic stimuli greatly outweigh the risks.

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Conflict of interest statement

Declaration of Interests PTK receives grants and/or contracts from Aligos and Vir Biotechnology; consulting fees from AssemblyBio, Bluejay Therapeutics, GlaxoSmithKline (GSK), and Gilead Sciences; honoraria from GSK and Gilead Sciences; and has a leadership role in the British Viral Hepatitis Group (Chair). MC receives funding from the Deutsche Zentrum für Infektionsforshung and the German Research Foundation; consulting fees from AbbVie (consulting; advisory board [hepatitis C]), AiCuris (consulting; advisory board [hepatitis B]), GSK (consulting; advisory board [hepatitis B]), Merck Sharpe and Dohme (consulting; advisory board [Covid and hepatitis B]), Roche (consulting; advisory board [hepatitis B]), AstraZeneca (consulting; advisory board [Covid]), and Gilead Sciences (consulting; advisory board [hepatitis B]); and honoraria from Abbvie (hepatitis C), Gilead Sciences (hepatitis D), and Falk (hepatitis); participates on an advisory board for Novartis; and has stock options in Biontech, unrelated to HBV. AJG receives support from Aligos Therapeutics, Bluejay Therapeutics, GSK, Roche, Vir Biotechnology, and EVOQ Therapeutics; and has participated in data safety monitoring boards or advisory boards to Aligos Therapeutics, Arbutus Biopharma, Assembly Biosciences, Bluejay Therapeutics, Gilead Sciences, GSK, Roche, Vir Biotechnology, and Virion therapeutics. LGG receives research funding from the Italian Ministry for University and Research (PE00000007 [INF-ACT], PRIN 20224NMLXK, and PRIN P2022Z8HNC), the Fondazione SAME Italy donation to support HBV research, and the Fondazione Prossimo Mio Italy donation to support HBV research; Sponsored Research Agreement (SRA) support from Gilead Sciences, Takis Biotechnology, and Avalia Immunotherapies; royalties from Scripps Research (payments to LGG as the creator of HBV transgenic mice) and license fees from Antios Therapeutics (for the selling of intellectual property related to CAMs; no longer active); consulting fees from Aligos Therapeutics, Ananda Immunotherapies, Antios Therapeutics, Arbutus Biopharma, Avalia Immunotherapies Chroma Medicine, Epsilen Bio, Genenta Science, and Gilead Sciences; has patents or planned patents UK 2018657.3 (Agents and methods for increasing liver immune response) and WO2021/160617 (Spirocyclic inhibitors of hepatitis B virus; at present the intellectual property is back to the investors [San Raffaele Hospital, LGG, and the Italian institutions Istituto Nazionale Genetica Molecolare and Istituto di Ricerca Biomedica]; the assets are no longer in development and not being marketed, and in the case of any future remuneration from it, including license fees and royalties, those would be shared between the inventors and the institutions they belong to); and stock or options from Genenta Science and Ananda Immunotherapies unrelated to HBV. HAK is Director of Operations for the International Coalition to Eliminate HBV. MLem has received consulting fees from Abbott Laboratories, Cepheid, and Gilead Sciences. MLev has received honoraria from AbbVie and Gilead Sciences, and travel support from AbbVie and Gilead Sciences. SGL receives research funding from Gilead Sciences, Abbott, and Sysmex through his institution; consulting fees from Gilead Sciences, Abbott, Roche, GSK, Janssen, Sysmex, Arbutus Biopharma, Assembly Biosciences, Grifols, AusperBio, and Aligos; honoraria from Gilead Sciences, Janssen, Roche, Sysmex, and GSK; travel support from GSK and Abbott; serves on a data safety monitoring board for Roche; and has unpaid leadership roles in ICE-HBV, AASLD, and Agence Nationale de Recherche sur le Sida et les hépatites–Maladies Infectieuses Emergentes. JET has unpaid roles on the Executive Committee of ICE-HBV and the Scientific and Medical Advisory Board to the Hepatitis B Foundation. BT receives research funding from Assembly Biosciences, Bluejay Therapeutics, Aligos, and Beam Therapeutics; has received fees for expert testimony from the International Hepatology Education Program; and has a patent pending with Beam Therapeutics for gRNA sequences targeting the HBV genome (not yet on the market; if the product reaches the market, remunerations would be split between Beam, INSERM, and the inventors [of note, the entire HBV programme including the development of this therapeutic strategy was stopped by Beam in 2023]). TT receives support through a Paul & Valeria Ainsworth Fellowship; research funding from Gilead Biosciences, ACH4, GESA, NSW Ministry of Health, National Health and Medical Research Council, and the Stephan Urban Foundation; consulting fees from Excision BioTherapeutics, Kerna Ventures, Gilead Sciences, and GSK; has received honoraria from GSK, ASHM, and the Science of HBV Cure Meeting 2024 in Singapore; has received travel support from GSK and the Science of HBV Cure Meeting; and has leadership roles in the Australian Centre for Hepatitis Virology, HepB Voices Australia, HepBcommunity.org, Hepatitis B Forum for Collaborative Research, Australian WHO Collaborating Centre, NSW Hepatitis B Strategy Implementation Program, the Hepatitis B Foundation, Australian National Hepatitis B Strategy Targets Workshop, the Australian Centre for HIV and Hepatitis Virology Research, ICE-HBV, ASHM, and Parramatta District Men's Shed. LA and AB declare no competing interests.

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Scientific and medical evidence informing expansion of hepatitis B treatment guidelines

Affiliations

Scientific and medical evidence informing expansion of hepatitis B treatment guidelines

Authors

Affiliations

Abstract

Conflict of interest statement

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