Update on the treatment navigation for functional cure of chronic hepatitis B: Expert consensus 2.0

Di Wu¹, Jia-Horng Kao², Teerha Piratvisuth³, Xiaojing Wang¹, Patrick T F Kennedy⁴, Motoyuki Otsuka⁵, Sang Hoon Ahn⁶, Yasuhito Tanaka⁷, Guiqiang Wang⁸, Zhenghong Yuan⁹, Wenhui Li¹⁰, Young-Suk Lim¹¹, Junqi Niu¹², Fengmin Lu¹³, Wenhong Zhang¹⁴, Zhiliang Gao¹⁵, Apichat Kaewdech¹⁶, Meifang Han¹, Weiming Yan¹, Hong Ren¹⁷, Peng Hu¹⁷, Sainan Shu¹⁸, Paul Yien Kwo¹⁹, Fu-Sheng Wang²⁰, Man-Fung Yuen²¹, Qin Ning¹

Affiliations

¹ Department of Infectious Diseases, Tongji Hospital, Tongji Medical College and State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Disease, Huazhong University of Science and Technology, Wuhan, China.
² Division of Gastroenterology and Hepatology, Department of Internal Medicine, Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan.
³ NKC Institute of Gastroenterology and Hepatology, Songklanagarind Hospital, Prince of Songkla University, Hat Yai, Thailand.
⁴ Barts Liver Centre, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
⁵ Department of Gastroenterology and Hepatology, Academic Fields of Medicine, Dentistry, and Pharmaceutical Science, Okayama University, Okayama, Japan.
⁶ Department of Internal Medicine, Yonsei University College of Medicine, Yonsei Liver Center, Severance Hospital, Seoul, Korea.
⁷ Department of Gastroenterology and Hepatology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
⁸ Department of Infectious Disease, Center for Liver Disease, Peking University First Hospital, Beijing, China.
⁹ Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), School of Basic Medical Sciences, Shanghai Medical College, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.
¹⁰ National Institute of Biological Sciences, Tsinghua Institute of Multidisciplinary Biomedical Research, Tsinghua University, Beijing, China.
¹¹ Department of Gastroenterology, Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
¹² Department of Hepatology, First Hospital of Jilin University, Jilin University, Jilin, China.
¹³ Department of Microbiology and Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China.
¹⁴ Department of Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, National Medical Center for Infectious Diseases, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China.
¹⁵ Department of Infectious Diseases, Guangdong Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.
¹⁶ Gastroenterology and Hepatology Unit, Division of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Hat Yai, Thailand.
¹⁷ Department of Infectious Diseases, Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China.
¹⁸ Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
¹⁹ Division of Gastroenterology and Hepatology, Stanford University Medical Center, Stanford University School of Medicine, Stanford, CA, USA.
²⁰ Department of Infectious Diseases, The Fifth Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Infectious Diseases, Beijing, China.
²¹ Department of Medicine, School of Clinical Medicine & State Key Laboratory of Liver Research, The University of Hong Kong, Queen Mary Hospital, Hong Kong SAR, China.

PMID: 39838828
PMCID: PMC11925436
DOI: 10.3350/cmh.2024.0780

Review

Update on the treatment navigation for functional cure of chronic hepatitis B: Expert consensus 2.0

Di Wu et al. Clin Mol Hepatol. 2025 Feb.

. 2025 Feb;31(Suppl):S134-S164.

doi: 10.3350/cmh.2024.0780. Epub 2025 Jan 22.

Authors

Affiliations

¹ Department of Infectious Diseases, Tongji Hospital, Tongji Medical College and State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Disease, Huazhong University of Science and Technology, Wuhan, China.
² Division of Gastroenterology and Hepatology, Department of Internal Medicine, Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan.
³ NKC Institute of Gastroenterology and Hepatology, Songklanagarind Hospital, Prince of Songkla University, Hat Yai, Thailand.
⁴ Barts Liver Centre, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
⁵ Department of Gastroenterology and Hepatology, Academic Fields of Medicine, Dentistry, and Pharmaceutical Science, Okayama University, Okayama, Japan.
⁶ Department of Internal Medicine, Yonsei University College of Medicine, Yonsei Liver Center, Severance Hospital, Seoul, Korea.
⁷ Department of Gastroenterology and Hepatology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
⁸ Department of Infectious Disease, Center for Liver Disease, Peking University First Hospital, Beijing, China.
⁹ Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), School of Basic Medical Sciences, Shanghai Medical College, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.
¹⁰ National Institute of Biological Sciences, Tsinghua Institute of Multidisciplinary Biomedical Research, Tsinghua University, Beijing, China.
¹¹ Department of Gastroenterology, Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
¹² Department of Hepatology, First Hospital of Jilin University, Jilin University, Jilin, China.
¹³ Department of Microbiology and Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China.
¹⁴ Department of Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, National Medical Center for Infectious Diseases, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China.
¹⁵ Department of Infectious Diseases, Guangdong Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.
¹⁶ Gastroenterology and Hepatology Unit, Division of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Hat Yai, Thailand.
¹⁷ Department of Infectious Diseases, Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China.
¹⁸ Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
¹⁹ Division of Gastroenterology and Hepatology, Stanford University Medical Center, Stanford University School of Medicine, Stanford, CA, USA.
²⁰ Department of Infectious Diseases, The Fifth Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Infectious Diseases, Beijing, China.
²¹ Department of Medicine, School of Clinical Medicine & State Key Laboratory of Liver Research, The University of Hong Kong, Queen Mary Hospital, Hong Kong SAR, China.

PMID: 39838828
PMCID: PMC11925436
DOI: 10.3350/cmh.2024.0780

Abstract

As new evidence emerges, treatment strategies toward the functional cure of chronic hepatitis B are evolving. In 2019, a panel of national hepatologists published a Consensus Statement on the functional cure of chronic hepatitis B. Currently, an international group of hepatologists has been assembled to evaluate research since the publication of the original consensus, and to collaboratively develop the updated statements. The 2.0 Consensus was aimed to update the original consensus with the latest available studies, and provide a comprehensive overview of the current relevant scientific literatures regarding functional cure of hepatitis B, with a particular focus on issues that are not yet fully clarified. These cover the definition of functional cure of hepatitis B, its mechanisms and barriers, the effective strategies and treatment roadmap to achieve this endpoint, in particular new surrogate biomarkers used to measure efficacy or to predict response, and the appropriate approach to pursuing a functional cure in special populations, the development of emerging antivirals and immunomodulators with potential for curing hepatitis B. The statements are primarily intended to offer international guidance for clinicians in their practice to enhance the functional cure rate of chronic hepatitis B.

Keywords: Antiviral Agents; Chronic hepatitis B; Consensus; HBsAg; Immunologic Factors.

PubMed Disclaimer

Conflict of interest statement

Conflicts of Interest

DW: Nothing to disclose. JHK: Nothing to disclose. TP: Research grants: Roche Diagnostic, Janssen, VIR, GSK, Sysmex; Honoraria: Roche, Takeda, DKSH, Viatris, Eisai, Astra Zeneca, Sysmex and American Taiwan Biopharm. XJW: Nothing to disclose. PTFK: Research grants: VIR Biotechnology Inc and Gilead Sciences; Consulting fees: Abbott Diagnostics, Aligos, BlueJay, Gilead Sciences, GSK, and Assembly Biosciences; Honoraria: Gilead Sciences and GSK. MO: Nothing to disclose. SHA: Nothing to disclose. YT: Research grants: Gilead Sciences, FUJIREBIO Inc, Sysmex Corp, Janssen Pharmaceutical K.K. and GSK; Honoraria: Gilead Sciences, GSK, and HU frontier. GQW: Nothing to disclose. ZHY: Nothing to disclose.

WHL: Nothing to disclose. YSL: Research grants, consulting fees and honoraria: Gilead Sciences. JQN: Nothing to disclose. FML: Nothing to disclose. WHZ: Nothing to disclose. ZLG: Nothing to disclose. AK: Research grants: Roche, Roche Diagnostics, and Abbott Laboratories; Honoraria: Roche, Roche Diagnostics, Abbott Laboratories, and Esai. MFH: Nothing to disclose. WMY: Nothing to disclose. HR: Nothing to disclose. PH: Nothing to disclose. SNS: Nothing to disclose. PYK: Research grants: Altimmune, Arrowhead, Gilead, Novo Nordisk, Target Registries, Ultragenyx, Salix, Madrigal, Ausper Bio, Takeda; Consulting fees: Abbvie, Aligos, Ausper Bio, Durect, Generon, Genentch, Gilead, Drug Farm, HepQuant, Inventiva, Mallinckrodt, Mirum, NovoNordisk, Surrozen. FSW: Nothing to disclose. MFY: Research grants: AbbVie, Assembly Biosciences, Arrowhead Pharmaceuticals, Fujirebio Incorporation, Gilead Sciences, Immunocore, Sysmex Corporation and Roche; Consulting fees: AbbVie, Abbott Diagnotics, Aligos Therapeutics, AiCuris, Antios Therapeutics, Arbutus Biopharma, Arrowhead Pharmaceuticals, Assembly Biosciences, Clear B Therapeutics, Dicerna Pharmaceuticals, Finch Therapeutics, Fujirebio Incorporation, GlaxoSmith-Kline, Gilead Sciences, Immunocore, Janssen, Precision BioSciences, Roche, Sysmex Corporation, Tune Therapeutics, Vir Biotechnology and Visirna Therapeutics; Honoraria: Fujirebio Incorporation, Gilead Sciences, Roche, Sysmex Corporation. QN: Research grants: MSD, Roche, NOVARTIS, BMS, Gilead Sciences and GSK; Consulting fees: MSD, Roche, NOVARTIS, BMS, Gilead Sciences and GSK.

Figures

**Figure 1.**
Navigation for combination of NA and Peg-IFN towards functional cure of hepatitis B.

**Figure 2.**
Proposed navigations for novel combination towards functional cure of hepatitis B. NA, nucleos(t)ide analogue; Peg-IFN, pegylated interferon-a; siRNA, small interfering RNA; ASO, antisense oligonucleotide; CpAM, core protein allosteric modulator; PD-1, Programmed Death-1, PD-L1, Programmed Death-Ligand 1; NAP, nucleic acid polymer; TLR, Toll-like receptor; HBsAg, hepatitis B surface antigen; HBeAg; hepatitis B e antigen; HBsAb, hepatitis B surface antibody.

See this image and copyright information in PMC

References

1. GBD 2019 Hepatitis B Collaborators Global, regional, and national burden of hepatitis B, 1990-2019: a systematic analysis for the Global Burden of Disease Study 2019. Lancet Gastroenterol Hepatol. 2022;7:796–829. - PMC - PubMed
1. WHO. Hepatitis B. WHO web site, < https://www.who.int/news-room/fact-sheets/detail/hepatitis-b> Accessed 1 Jan 2025.
1. Ning Q, Wu D, Wang GQ, Ren H, Gao ZL, Hu P, et al. Roadmap to functional cure of chronic hepatitis B: An expert consensus. J Viral Hepat. 2019;26:1146–1155. - PubMed
1. Yip TC, Wong GL, Chan HL, Tse YK, Lam KL, Lui GC, et al. HBsAg seroclearance further reduces hepatocellular carcinoma risk after complete viral suppression with nucleos(t)ide analogues. J Hepatol. 2019;70:361–370. - PubMed
1. Kim MA, Kim SU, Sinn DH, Jang JW, Lim YS, Ahn SH, et al. Discontinuation of nucleos(t)ide analogues is not associated with a higher risk of HBsAg seroreversion after antiviral-induced HBsAg seroclearance: a nationwide multicentre study. Gut. 2020;69:2214–2222. - PubMed

Publication types

Actions
Actions

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

Update on the treatment navigation for functional cure of chronic hepatitis B: Expert consensus 2.0

Affiliations

Update on the treatment navigation for functional cure of chronic hepatitis B: Expert consensus 2.0

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

Publication types

MeSH terms

Substances

Grants and funding

LinkOut - more resources

Full Text Sources

Research Materials