1
|
Li D, Ho V, Teng CF, Tsai HW, Liu Y, Bae S, Ajoyan H, Wettengel JM, Protzer U, Gloss BS, Rockett RJ, Al Asady R, Li J, So S, George J, Douglas MW, Tu T. Novel digital droplet inverse PCR assay shows that natural clearance of hepatitis B infection is associated with fewer viral integrations. Emerg Microbes Infect 2025; 14:2450025. [PMID: 39749570 PMCID: PMC11731057 DOI: 10.1080/22221751.2025.2450025] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2024] [Revised: 12/30/2024] [Accepted: 01/01/2025] [Indexed: 01/04/2025]
Abstract
Hepatitis B virus (HBV) DNA integration into the host cell genome is reportedly a major cause of liver cancer, and a source of hepatitis B surface antigen (HBsAg). High HBsAg levels can alter immune responses which therefore contributes to the progression of HBV-related disease. However, to what extent integration leads to the persistent circulating HBsAg is unclear. Here, we aimed to determine if the extent of HBV DNA integration is associated with the persistence of circulating HBsAg in people exposed to HBV. We established a digital droplet quantitative inverse PCR (dd-qinvPCR) method to quantify integrated HBV DNA in patients who had been exposed to HBV (anti-HBc positive and HBeAg-negative). Total DNA extracts from both liver resections (n = 32; 14 HBsAg-negative and 18 HBsAg-positive) and fine-needle aspirates (FNA, n = 10; 2 HBsAg-negative and 8 HBsAg-positive) were analysed. Using defined in vitro samples for assay establishment, we showed that dd-qinvPCR could detect integrations within an input of <80 cells. The frequency of integrated HBV DNA in those who had undergone HBsAg loss (n = 14, mean ± SD of 1.514 × 10-3 ± 1.839 × 10-3 integrations per cell) was on average 9-fold lower than those with active HBV infection (n = 18, 1.16 × 10-2 ± 1.76 × 10-2 integrations per cell; p = 0.0179). In conclusion, we have developed and validated a highly precise, sensitive and quantitative PCR-based method for the quantification of HBV integrations in clinical samples. Natural clearance of HBV is associated with fewer viral integrations. Future studies are needed to determine if dynamics of integrated HBV DNA can inform the development of curative therapies.
Collapse
Affiliation(s)
- Dong Li
- Storr Liver Centre, The Westmead Institute for Medical Research, Westmead Hospital and The University of Sydney, Westmead, NSW, Australia
| | - Vikki Ho
- Storr Liver Centre, The Westmead Institute for Medical Research, Westmead Hospital and The University of Sydney, Westmead, NSW, Australia
| | - Chiao-Fang Teng
- Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan
- Program for Cancer Biology and Drug Discovery, China Medical University, Taichung, Taiwan
- Organ Transplantation Center, China Medical University Hospital, Taichung, Taiwan
| | - Hung-Wen Tsai
- Department of Pathology, National Cheng Kung University Hospital, Tainan, Taiwan
| | - Yuanyuan Liu
- Storr Liver Centre, The Westmead Institute for Medical Research, Westmead Hospital and The University of Sydney, Westmead, NSW, Australia
| | - Sarah Bae
- Storr Liver Centre, The Westmead Institute for Medical Research, Westmead Hospital and The University of Sydney, Westmead, NSW, Australia
| | - Harout Ajoyan
- Storr Liver Centre, The Westmead Institute for Medical Research, Westmead Hospital and The University of Sydney, Westmead, NSW, Australia
| | - Jochen M. Wettengel
- Institute of Virology, Technische Universität München/Helmholtz Zentrum München, Munich, Germany
- German Center for Infection Research (DZIF), Munich Partner Site, Munich, Germany
| | - Ulrike Protzer
- Institute of Virology, Technische Universität München/Helmholtz Zentrum München, Munich, Germany
- German Center for Infection Research (DZIF), Munich Partner Site, Munich, Germany
| | - Brian S. Gloss
- Scientific Platforms, The Westmead Institute for Medical Research, The University of Sydney, Westmead, NSW, Australia
| | - Rebecca J. Rockett
- Centre for Infectious Diseases and Microbiology–Public Health, Westmead Hospital, Westmead, NSW, Australia
| | - Rafid Al Asady
- Department of Radiology, Westmead Hospital, Westmead, NSW, Australia
| | - Jane Li
- Department of Radiology, Westmead Hospital, Westmead, NSW, Australia
| | - Simon So
- Department of Radiology, Westmead Hospital, Westmead, NSW, Australia
| | - Jacob George
- Storr Liver Centre, The Westmead Institute for Medical Research, Westmead Hospital and The University of Sydney, Westmead, NSW, Australia
| | - Mark W. Douglas
- Storr Liver Centre, The Westmead Institute for Medical Research, Westmead Hospital and The University of Sydney, Westmead, NSW, Australia
| | - Thomas Tu
- Storr Liver Centre, The Westmead Institute for Medical Research, Westmead Hospital and The University of Sydney, Westmead, NSW, Australia
| |
Collapse
|
2
|
Oludoun O, Abiodun O, Gbadamosi B, Oladejo J, Akinola E, Emuoyibofarhe O, Adebimpe O. The role of spontaneous clearance on fractional analysis of HBV. Infect Dis Model 2025; 10:1019-1036. [PMID: 40520250 PMCID: PMC12167083 DOI: 10.1016/j.idm.2025.05.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2025] [Revised: 05/13/2025] [Accepted: 05/23/2025] [Indexed: 06/18/2025] Open
Abstract
Hepatitis B virus (HBV) remains a persistent global health concern, with recent research advancing our understanding of its transmission dynamics and potential interventions.The present study proposes a mathematical model of Hepatitis B Virus (HBV) epidemics using fractional calculus, with a special emphasis on the influence of spontaneous clearance across diverse population groups. Using the Atangana-Baleanu derivative, the model accounts for the complications of vertical and horizontal transmission, therapy, immunisation, and spontaneous clearance. Numerical simulations with different fractional orders demonstrate how spontaneous clearance affects the dynamics of susceptible, chronic, treated, and recovered populations. The findings indicate that in vulnerable populations, increasing spontaneous clearance reduces vulnerability because people either clear the illness naturally or gain resistance.However, in chronic populations, spontaneous clearance is insufficient for complete recovery without treatment. The combination of therapy and spontaneous clearance improves the treated population, demonstrating the beneficial effects of both medical intervention and natural immunity. Furthermore, increased spontaneous clearance boosts the restored population, demonstrating the immune system's ability to eliminate the virus over time. The fractional-order framework captures the memory effect of illness development, revealing how healing is time-dependent and how immune responses have a long-term impact. This study emphasises the need of combining spontaneous clearance with medical therapies to improve HBV management and public health consequences. Hepatitis B virus (HBV) remains a persistent global health concern, with recent research advancing our understanding of its transmission dynamics and potential interventions. This study presents a fractional mathematical model of HBV infection, employing the Atangana-Baleanu derivative with Mittag-Leffler kernels to capture memory-dependent and nonlocal transmission processes. The model integrates vertical and horizontal transmission pathways, treatment strategies, immunization efforts, and spontaneous clearance, providing a nuanced perspective compared to classical models. Stability conditions are analyzed through fixed-point theory, revealing the global stability of both disease-free and endemic states under specific values of the basic reproduction number R 0. Numerical simulations demonstrate the model's effectiveness in capturing the complex dynamics of HBV, with fractional-order parameters enhancing prediction accuracy. This approach offers valuable insights into optimizing public health interventions and treatment strategies for managing HBV infections effectively.
Collapse
Affiliation(s)
- O.Y. Oludoun
- Department of Mathematics, Bowen University, Iwo, Nigeria
| | - O. Abiodun
- Department of Mathematics and Statistics, First Technical University, Oyo State, Nigeria
| | - B. Gbadamosi
- Department of Mathematics and Statistics, First Technical University, Oyo State, Nigeria
| | - J.K. Oladejo
- Department of Mathematics, Ladoke Akintola University of Technology, Ogbomoso, Nigeria
| | - E.I. Akinola
- Department of Mathematics, Bowen University, Iwo, Nigeria
| | | | - O. Adebimpe
- Department of Mathematics and Statistics, First Technical University, Oyo State, Nigeria
| |
Collapse
|
3
|
Wang X, Lai C, Li R, Lei J, Xie Y, Li Z, Tang Q, He Q, Zhang H, Zhang Z, Wang F. High HBsAg clearance rate and viral dynamics in HBeAg-positive, ALT-normal children and adolescents with chronic HBV infection: results from the prospective sprout project. Emerg Microbes Infect 2025; 14:2516173. [PMID: 40469009 DOI: 10.1080/22221751.2025.2516173] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2025] [Revised: 04/22/2025] [Accepted: 05/30/2025] [Indexed: 06/28/2025]
Abstract
Hepatitis B e antigen (HBeAg)-positive chronic hepatitis B virus (HBV) infection in children and adolescents with normal alanine aminotransferase (ALT) levels constitutes a substantial population in China, yet the optimal timing for antiviral therapy remains unclear. This prospective, real-world study, conducted as the primary centre of the Sprout Project, evaluated the hepatitis B surface antigen (HBsAg) loss rate and viral-immune dynamics of pegylated interferon α (PEG-IFN-α) treatment in 85 chronic HBV patients aged 3-18 years over a 24-month period. A total of 27 HBeAg-positive, ALT-normal patients were selected for analysis. Patients were treated with a combination of PEG-IFN-α and entecavir. After 24 months, the overall HBsAg loss rate was 48.15%, with 47.37% in the immune-tolerant phase and 50% in the grey zone phase. Among those who cleared HBsAg, 84.62% had ALT elevation prior to anti-HBsAg antibody (HBsAb) seroconversion, which occurred 28-400 days before HBsAg loss. While HBsAg and HBV DNA were cleared by 24 months in the HBsAg loss group, 23.08% of children remained HBeAg-positive. Notably, 61.54% developed detectable HBsAb prior to HBsAg loss. Children aged 3-7 years had significantly higher clearance rates than those aged 8-18 years. These findings support the effectiveness of PEG-IFN-α combined with nucleos(t)ide analogs in achieving high HBsAg loss rates in young, HBeAg-positive, ALT-normal chronic HBV children and adolescents, with immune activation potentially preceding ALT elevation, and offers valuable insights into the viral-immune dynamics during treatment, highlighting the potential of antiviral therapy in this population.
Collapse
Affiliation(s)
- Xin Wang
- Institute for Hepatology, National Clinical Research Center for Infectious Disease, Shenzhen Third People's Hospital; The Second Affiliated Hospital, School of Medicine, Southern University of Science and Technology, Shenzhen, People's Republic of China
| | - Changxiang Lai
- Department of Liver Diseases, National Clinical Research Center for Infectious Disease, Shenzhen Third People's Hospital, Shenzhen, People's Republic of China
| | - Ruiling Li
- Department of Infectious Diseases, The Affiliated Hospital, Southwest Medical University, Luzhou, Sichuan, People's Republic of China
| | - Jia Lei
- Institute for Hepatology, National Clinical Research Center for Infectious Disease, Shenzhen Third People's Hospital; The Second Affiliated Hospital, School of Medicine, Southern University of Science and Technology, Shenzhen, People's Republic of China
| | - Yuyin Xie
- School of Intelligent Medicine and Biotechnology, Guilin Medical University, Guilin, Guangxi, People's Republic of China
| | - Zhiyu Li
- Department of Liver Diseases, National Clinical Research Center for Infectious Disease, Shenzhen Third People's Hospital, Shenzhen, People's Republic of China
| | - Qiyuan Tang
- Department of Liver Diseases, National Clinical Research Center for Infectious Disease, Shenzhen Third People's Hospital, Shenzhen, People's Republic of China
| | - Qing He
- Department of Liver Diseases, National Clinical Research Center for Infectious Disease, Shenzhen Third People's Hospital, Shenzhen, People's Republic of China
| | - Hongfei Zhang
- Beijing Chen Jumei Foundation, Beijing, People's Republic of China
| | - Zheng Zhang
- Institute for Hepatology, National Clinical Research Center for Infectious Disease, Shenzhen Third People's Hospital; The Second Affiliated Hospital, School of Medicine, Southern University of Science and Technology, Shenzhen, People's Republic of China
- Department of Infectious Diseases, The Affiliated Hospital, Southwest Medical University, Luzhou, Sichuan, People's Republic of China
| | - Fang Wang
- Department of Liver Diseases, National Clinical Research Center for Infectious Disease, Shenzhen Third People's Hospital, Shenzhen, People's Republic of China
| |
Collapse
|
4
|
Ding L, Huang J, Huang S. The significance of antibody to hepatitis B surface antigen in infection and clearance of hepatitis B virus. Hum Vaccin Immunother 2025; 21:2445283. [PMID: 39754388 DOI: 10.1080/21645515.2024.2445283] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2024] [Revised: 11/30/2024] [Accepted: 12/17/2024] [Indexed: 01/06/2025] Open
Abstract
One of the key features of chronic hepatitis B virus (HBV) infection is the inability to mount sufficient and coordinated adaptive immune responses against HBV. Recent studies on HBV-specific B cells and antibody to hepatitis B surface antigen (anti-HBs) have shed light on their role in the pathogenesis of chronic hepatitis B (CHB). Anti-HBs is recognized as a protective immune marker, both for HBV infection clearance and following vaccination, and it is also considered an important indicator of functional cure for CHB. Notably, functional impairment of HBV-specific B cells may be reversible. The restoration of HBV-specific B cell function, along with the induction of an anti-HBs antibody response, is regarded as pivotal for terminating chronic HBV infection and achieving functional cure. This article reviews the significance of anti-HBs in both the infection and clearance of HBV, and discusses the potential of neutralizing antibodies and therapeutic vaccines as promising future strategies.
Collapse
Affiliation(s)
- Ling Ding
- Department of General Practice, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Jiaquan Huang
- Department and Institute of Infectious Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Shuaiwen Huang
- Department of General Practice, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Division of Nephrology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Department of Nutrition, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| |
Collapse
|
5
|
Zhang L, Zhang Q, Liu J, Wu W, Jiang Z, Yan B, Cao Q, Liu H, Pan H, Lv J, Feng Y, Xu F, Huang S, Xu A. Immunogenicity and safety of HepE Hecolin® in chronic hepatitis B patients at clinically stable stage: An open-label study in China. Hum Vaccin Immunother 2025; 21:2448882. [PMID: 39797410 PMCID: PMC11730616 DOI: 10.1080/21645515.2024.2448882] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2024] [Revised: 12/24/2024] [Accepted: 12/28/2024] [Indexed: 01/15/2025] Open
Abstract
Acute hepatitis E infection could induce severe outcomes among chronic hepatitis B (CHB) patients. Between 2016 and 2017, an open-label study was conducted to evaluate the immunogenicity and safety of hepatitis E vaccine (HepE) in CHB patients, using healthy adults as parallel controls in China. Eligible participants who were aged ≥30 y were enrolled in the study. The CHB group included participants who had ever developed symptoms of hepatitis because of CHB but was currently at a clinically stable stage, which was defined as ALT ≤ 1.5 times of upper limit of the normal range (ULN) in this study. The control group included healthy adults who had hepatitis B surface antigen (HBsAg) negative. HepE was administered for 0, 1, 6 months for all participants. At 1 month after the third-dose vaccination (month 7), the seroconversion rates of anti-HEV IgG were >97% in both groups. The geometric mean concentration (GMC) of anti-HEV IgG in the CHB group was non-inferior to the healthy adult group (0.69 WU/mL, 95% CI 0.55-0.85). The proportion of the participants with adverse events ≥ grade 3 was similar in both groups (p = .99), and no vaccine-associated severe adverse events were identified. Changes in the liver function indicators were not of clinical significance. The HepE was highly immunogenic and well tolerated among clinically stable CHB patients and healthy adults.
Collapse
Affiliation(s)
- Li Zhang
- Academy of Preventive Medicine, Shandong University, Jinan, China
- Shandong Provincial Key Laboratory of Infectious Disease Control and Prevention, Shandong Center for Disease Control and Prevention, Jinan, China
| | - Qiufen Zhang
- Department of Medicine, Xiamen Innovax Biotech Co. Ltd, Xiamen, China
| | - Jiaye Liu
- School of Public Health, Shenzhen University Medical School, Shenzhen, China
| | - Wenlong Wu
- Shandong Provincial Key Laboratory of Infectious Disease Control and Prevention, Shandong Center for Disease Control and Prevention, Jinan, China
| | - Zechun Jiang
- Division of Expanded Program Immunization, Rushan Center for Disease Control and Prevention, Rushan, China
| | - Bingyu Yan
- Shandong Provincial Key Laboratory of Infectious Disease Control and Prevention, Shandong Center for Disease Control and Prevention, Jinan, China
| | - Qingfan Cao
- Division of Expanded Program Immunization, Rushan Center for Disease Control and Prevention, Rushan, China
| | - Haidong Liu
- Division of Expanded Program Immunization, Rushan Center for Disease Control and Prevention, Rushan, China
| | - Huirong Pan
- Department of Medicine, Xiamen Innovax Biotech Co. Ltd, Xiamen, China
| | - Jingjing Lv
- Shandong Provincial Key Laboratory of Infectious Disease Control and Prevention, Shandong Center for Disease Control and Prevention, Jinan, China
| | - Yi Feng
- Shandong Provincial Key Laboratory of Infectious Disease Control and Prevention, Shandong Center for Disease Control and Prevention, Jinan, China
| | - Fujie Xu
- Global Health Research Center, Duke Kunshan University, Kunshan, China
| | - Shoujie Huang
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, Strait Collaborative Innovation Center of Biomedicine and Pharmaceutics, School of Public Health, Xiamen University, China
| | - Aiqiang Xu
- Academy of Preventive Medicine, Shandong University, Jinan, China
- Shandong Provincial Key Laboratory of Infectious Disease Control and Prevention, Shandong Center for Disease Control and Prevention, Jinan, China
| |
Collapse
|
6
|
Coignard C, Vincent C, Lemée V, Plantier JC, Gautier J, Leboulaire F, Turini M, Demirdjian G, Karagueuzian M, Roulet V, Hey J, Rhodes DW. Performance evaluation of the access anti-HBc IgM Assay on the DxI 9000 access immunoassay analyzer. Diagn Microbiol Infect Dis 2025; 112:116862. [PMID: 40305958 DOI: 10.1016/j.diagmicrobio.2025.116862] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2025] [Revised: 04/15/2025] [Accepted: 04/16/2025] [Indexed: 05/02/2025]
Abstract
This study evaluated the diagnostic and analytical performances of the Access anti-HBc IgM assay (Access assay) for use on the DxI 9000 Access Immunoassay Analyzer. Prospectively and retrospectively collected samples were tested with Access and a comparator assay with use of a second comparator for discrepant resolution to determine final anti-HBc IgM sample status. Specificity of Access was 100.00 % (99.65 - 100.00 %) on 1,098 anti-HBc IgM negative blood donor samples, 100.00 % (98.74 - 100.00 %) on 300 anti-HBc IgM negative hospitalized patient samples and 94.08 % (89.45 - 96.75 %) on 169 anti-HBc IgM negative acute/recent and chronic HBV infected patient samples. Sensitivity was 100.00 % (98.42 - 100.00 %) on 239 anti-HBc IgM positive acute/recent and chronic HBV infected patient samples. Seroconversion panels showed mean first day of detection 3.2 days earlier with Access than with the comparator assay. Maximum reproducibility on positive samples was 8.6 % coefficient of variance (CV) and 0.048 S/CO standard deviation (SD) on negative samples. The Access anti-HBc IgM assay demonstrated excellent diagnostic and analytical performances comparable to other current CE-marked anti-HBc IgM assays.
Collapse
Affiliation(s)
- Catherine Coignard
- Infectiology, Specialized CoreLab Department, Eurofins Biomnis, Ivry-Sur-Seine, France
| | - Claire Vincent
- Biomnis Sample Library Department, Eurofins Biomnis, Ivry-Sur-Seine, France
| | - Veronique Lemée
- CHU Rouen, Department of Virology, National Reference Center of HIV, F-76000 Rouen, France; Univ Rouen Normandie, Univ de Caen, INSERM, DYNAMICURE UMR 1311, Department of Virology, National Reference Center of HIV, CHU Rouen, F-76000 Rouen, France
| | - Jean-Christophe Plantier
- CHU Rouen, Department of Virology, National Reference Center of HIV, F-76000 Rouen, France; Univ Rouen Normandie, Univ de Caen, INSERM, DYNAMICURE UMR 1311, Department of Virology, National Reference Center of HIV, CHU Rouen, F-76000 Rouen, France
| | | | | | - Marc Turini
- R&D Department, Beckman Coulter, Immunotech, Marseille, France
| | | | | | - Vanessa Roulet
- Clinical Affairs Department, Beckman Coulter, Immunotech, Marseille, France
| | - Juliane Hey
- Clinical Affairs Department, Beckman Coulter, Immunotech, Marseille, France
| | - Dan W Rhodes
- Clinical Affairs Department, Beckman Coulter, Immunotech, Marseille, France.
| |
Collapse
|
7
|
Pfefferkorn M, Brehm J, Brehm M, Honshoven F, Deichsel D, Vernoux L, Pavlovic V, Wat C, Berg T, van Bömmel F. Overrange dilution for improvement of hepatitis B core related antigen as a biomarker: protocol validation and examples for application. Virology 2025; 609:110576. [PMID: 40393306 DOI: 10.1016/j.virol.2025.110576] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2024] [Revised: 04/14/2025] [Accepted: 05/14/2025] [Indexed: 05/22/2025]
Abstract
BACKGROUND Hepatitis B core related antigen (HBcrAg) measurement predicts treatment outcomes and reflects intrahepatic HBV replication. The commercially available automated assay for HBcrAg has a linear range of 3.0 - 7.0 logU/mL, with higher levels requiring dilution. However, using different diluents across studies may impact comparability and cross-reactivity, which has not been thoroughly investigated. This study aims to validate a dilution method for specimens above the upper limit of quantification (7.0 logU/mL) to improve comparability. METHODS The dilution procedure was two-site tested with three matrices for practicability, accuracy and repeatability using samples from HBV-infected patients with high HBcrAg levels. Samples were tested undiluted or diluted when overrange using Fujirebio's specific dilution reagent (SD1) with reflex testing of pre-treated samples, or manually diluted with fetal calf serum (FCS) or human serum (HS) of samples before restarting pre-treatment. Overrange dilution was further validated in three patient cohorts: untreated HBV-infected patients (n = 157) and patients treated with nucleos(t)ide analogues (NA, n = 19), or pegylated interferon-2alpha (PEG-IFN, n = 80) RESULTS: On-board dilution with SD1 showed higher background signals compared to HS or FCS. The dilution process was reproducible across sites, but SD1 underestimated HBcrAg levels. Dilution with FCS showed an early decrease in HBcrAg levels in patients with HBeAg SC during NA treatment (after 3 months, p = 0.022) and PEG-IFN treatment, whereas no change in HBcrAg levels was found without overrange dilution. CONCLUSION Validation showed high background and underestimating levels of HBcrAg with SD1, while FCS-based overrange dilution resulted in significant early HBcrAg decreases and better correlation with treatment response.
Collapse
Affiliation(s)
- Maria Pfefferkorn
- Division of Hepatology, Department of Medicine II, Leipzig University Medical Center, Leipzig, Germany.
| | | | | | | | - Danilo Deichsel
- Division of Hepatology, Department of Medicine II, Leipzig University Medical Center, Leipzig, Germany
| | | | | | | | - Thomas Berg
- Division of Hepatology, Department of Medicine II, Leipzig University Medical Center, Leipzig, Germany
| | - Florian van Bömmel
- Division of Hepatology, Department of Medicine II, Leipzig University Medical Center, Leipzig, Germany
| |
Collapse
|
8
|
Vinh DC. Host-directed immunotherapy for viral infections. Curr Opin Infect Dis 2025; 38:313-321. [PMID: 40396398 DOI: 10.1097/qco.0000000000001116] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/22/2025]
Abstract
PURPOSE OF REVIEW The limitations of pathogen-directed therapies include growing antimicrobial resistance or the complete lack of any effective antimicrobial agents. This review highlights the potential for host-directed immunotherapies. RECENT FINDINGS This review provides a current status of host-directed immunotherapies to fight infectious diseases (HIFI), defining the concept and existing modalities. Drawing on large-scale viral studies - most of which are historical with limited recent research - the review highlights key lessons for its future clinical application. SUMMARY HIFI represents a paradigm shift in infectious disease management, moving beyond pathogen-targeting to harnessing and modulating host immunity. This approach requires better mechanistic and pharmacologic understanding of existing modalities, development of newer agents based on tractable immunobiology, and robust clinical studies.
Collapse
Affiliation(s)
- Donald C Vinh
- Department of Medicine (Division of Infectious Diseases)
- Department of OptiLab (Division of Medical Microbiology, Division of Molecular Genetics-Immunology), McGill University Health Centre
- Department of Human Genetics, McGill University
- Centre of Reference for Genetic Research in Infection and Immunity, Research Institute - McGill University Health Centre, Montreal, Quebec, Canada
| |
Collapse
|
9
|
Yeap V, Liou WL, Morvil G, Kumar R. Real-world Prevalence of Hepatitis B Reactivation in Patients With Resolved Hepatitis B Receiving Rituximab and Non-rituximab-based Immunosuppressive Therapy Without Chemoprophylaxis. J Clin Exp Hepatol 2025; 15:102551. [PMID: 40276702 PMCID: PMC12018034 DOI: 10.1016/j.jceh.2025.102551] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/06/2024] [Accepted: 03/16/2025] [Indexed: 04/26/2025] Open
Abstract
Background Hepatitis B virus reactivation (HBVr) can occur in patients with resolved hepatitis B virus (HBV) infection receiving immunosuppressive therapy. The class of immunosuppression influences HBV reactivation (HBVr) risk, with B-cell depleting agents such as Rituximab conferring a higher risk. The presence of hepatitis B surface antibodies (HBsAb) may be protective against HBVr. Objective To compare the rates of HBVr amongst individuals with resolved HBV infection receiving rituximab and non-rituximab immunosuppressive therapy, without chemoprophylaxis. Our secondary objective was to explore the role of HBsAb in risk stratification for HBVr. Methods We retrospectively collected the data of patients with resolved HBV infection receiving immunosuppressants between 2014 and 2022. HBVr rates amongst patients receiving rituximab and non-rituximab therapy were compared. Logistic regression analysis was performed to identify risk factors for HBVr. Results 148 patients with resolved HBV infection did not receive chemoprophylaxis. Of the 20 (13.5%) patients who developed HBVr, none developed HBV flare. 42 of the 148 (28.3%) patients received rituximab-based therapy. Patients who received rituximab had a higher risk of HBVr, 12(28.6%) vs 8(7.5%), P = 0.001. This was confirmed on multivariable analysis (OR 4.19 [C.I. 1.47-11.9], P = 0.007). HBsAb titres of above 100 mIU/ml were protective against HBVr (OR 0.04 [CI 0.001-0.84], P = 0.039) in the rituximab exposed cohort, but not in the non-rituximab exposed cohort. Conclusion The risk of HBVr was higher in patients receiving rituximab; however, no patient developed HBV flare. In patients with resolved HBV infection, the presence of HBsAb titres above 100 mIU/ml may confer additional protection against HBVr and can be used as part of risk stratification for HBVr. In such patients, close surveillance with on-demand therapy instead of chemoprophylaxis may be considered.
Collapse
Affiliation(s)
- Valerie Yeap
- Department of Gastroenterology and Hepatology, Singapore General Hospital, Singapore
| | - Wei-Lun Liou
- Department of Gastroenterology and Hepatology, Singapore General Hospital, Singapore
| | - Gayathry Morvil
- Department of Gastroenterology and Hepatology, Singapore General Hospital, Singapore
| | - Rajneesh Kumar
- Department of Gastroenterology and Hepatology, Singapore General Hospital, Singapore
| |
Collapse
|
10
|
Pan X, Zhou L, Hu J, Zhai P, Ou X, He F, Pan CQ. Tenofovir Alafenamide Therapy Throughout Pregnancy in Mothers With Hepatitis B. Aliment Pharmacol Ther 2025; 62:159-167. [PMID: 40318163 DOI: 10.1111/apt.70173] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/03/2025] [Revised: 02/11/2025] [Accepted: 04/16/2025] [Indexed: 05/07/2025]
Abstract
BACKGROUND Mothers with chronic hepatitis B and advanced fibrosis may require antiviral therapy throughout pregnancy. Current guidelines recommend tenofovir disoproxil fumarate (TDF), which is unsuitable for mothers at risk of renal dysfunction or decreased bone mineral density. AIMS This study aimed to evaluate the safety of tenofovir alafenamide (TAF) therapy during pregnancy. METHODS Mothers with chronic hepatitis B treated with TAF or no therapy were retrospectively enrolled and categorised into three groups: (A) TAF-first trimester, (B) TAF-late trimester and (C) no treatment. Propensity score matching was applied to create comparable groups. Primary assessments included serious adverse events up to postpartum week 28, while secondary assessments examined predictors of such events and vertical transmission rates. RESULTS Among 284 mothers, 160 were selected. No significant differences were observed in foetal loss, low birth weight, preterm delivery or congenital abnormalities between groups A and B, or between groups A and C. Other adverse events were similar across groups, except for a higher incidence of gestational diabetes in the TAF-first trimester group. In vitro fertilisation was identified as the sole predictor of serious events. No infants were reported with hepatitis B virus infection at 28 weeks postpartum. CONCLUSIONS This study suggests that TAF treatment throughout pregnancy is safe for mothers with chronic hepatitis B and their infants. TAF therapy represents a viable treatment option for these mothers.
Collapse
Affiliation(s)
- Xingfei Pan
- Department of Infectious Diseases, Guangdong Provincial Key Laboratory of Major Obstetric Diseases; Guangdong Provincial Clinical Research Center for Obstetrics and Gynecology, The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou, China
| | - Liyang Zhou
- Department of Infectious Diseases, Guangdong Provincial Key Laboratory of Major Obstetric Diseases; Guangdong Provincial Clinical Research Center for Obstetrics and Gynecology, The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou, China
| | - Jing Hu
- Department of Obstetrics and Gynecology, Department of Obstetrics, Guangdong Provincial Key Laboratory of Major Obstetric Diseases; Guangdong Provincial Clinical Research Center for Obstetrics and Gynecology; Guangdong-Hong Kong-Macao Greater Bay Area Higher Education Joint Laboratory of Maternal-Fetal Medicine, The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou, China
| | - Panpan Zhai
- Department of Infectious Diseases, Guangdong Provincial Key Laboratory of Major Obstetric Diseases; Guangdong Provincial Clinical Research Center for Obstetrics and Gynecology, The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou, China
| | - Xueting Ou
- Department of Infectious Diseases, Guangdong Provincial Key Laboratory of Major Obstetric Diseases; Guangdong Provincial Clinical Research Center for Obstetrics and Gynecology, The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou, China
| | - Fang He
- Department of Obstetrics and Gynecology, Department of Obstetrics, Guangdong Provincial Key Laboratory of Major Obstetric Diseases; Guangdong Provincial Clinical Research Center for Obstetrics and Gynecology; Guangdong-Hong Kong-Macao Greater Bay Area Higher Education Joint Laboratory of Maternal-Fetal Medicine, The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou, China
- Department of Obstetrics and Gynecology, Guangdong Provincial Key Laboratory of Major Obstetric Diseases; Guangdong Provincial Clinical Research Center for Obstetrics and Gynecology; Guangdong-Hong Kong-Macao Greater Bay Area Higher Education Joint Laboratory of Maternal-Fetal Medicine, The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou, China
| | - Calvin Q Pan
- Guangzhou Medical University, Guangzhou, China
- Division of Gastroenterology and Hepatology, Department of Medicine, NYU Langone Health, NYU Grossman School of Medicine, New York, USA
| |
Collapse
|
11
|
Adlat S, Vázquez Salgado AM, Lee M, Yin D, Wangensteen KJ. Emerging and potential use of CRISPR in human liver disease. Hepatology 2025; 82:232-253. [PMID: 37607734 PMCID: PMC10881897 DOI: 10.1097/hep.0000000000000578] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/17/2023] [Accepted: 08/13/2023] [Indexed: 08/24/2023]
Abstract
CRISPR is a gene editing tool adapted from naturally occurring defense systems from bacteria. It is a technology that is revolutionizing the interrogation of gene functions in driving liver disease, especially through genetic screens and by facilitating animal knockout and knockin models. It is being used in models of liver disease to identify which genes are critical for liver pathology, especially in genetic liver disease, hepatitis, and in cancer initiation and progression. It holds tremendous promise in treating human diseases directly by editing DNA. It could disable gene function in the case of expression of a maladaptive protein, such as blocking transthyretin as a therapy for amyloidosis, or to correct gene defects, such as restoring the normal functions of liver enzymes fumarylacetoacetate hydrolase or alpha-1 antitrypsin. It is also being studied for treatment of hepatitis B infection. CRISPR is an exciting, evolving technology that is facilitating gene characterization and discovery in liver disease and holds the potential to treat liver diseases safely and permanently.
Collapse
Affiliation(s)
- Salah Adlat
- Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, Minnesota, USA
| | | | | | | | | |
Collapse
|
12
|
Romeo M, Dallio M, Cipullo M, Coppola A, Mazzarella C, Mammone S, Iadanza G, Napolitano C, Vaia P, Ventriglia L, Federico A. Nutritional and Psychological Support as a Multidisciplinary Coordinated Approach in the Management of Chronic Liver Disease: A Scoping Review. Nutr Rev 2025; 83:1327-1343. [PMID: 39992295 DOI: 10.1093/nutrit/nuaf001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/25/2025] Open
Abstract
OBJECTIVES This review emphasizes a novel, multidisciplinary, coordinated approach in the management of chronic liver diseases (CLDs). BACKGROUND Chronic liver diseases represent a significant global health burden, marked by a notable shift in the prevalence patterns from virus-related to metabolic and alcohol-related entities. Malnutrition, frailty, and sarcopenia exert a substantial impact on patients with cirrhosis, affecting 75%-90% of cases and escalating as the disease progresses. The European Association for the Study of the Liver recommends a comprehensive approach to nutritional care, emphasizing the need for detailed assessments in patients with cirrhosis, using diverse tools such as computed tomography scans, bioelectrical impedance analysis, and evaluations of muscle function. Considering the prevalence of nutritional and psychological disorders in the CLD population, the treatment of these patients should be founded indispensably on a multidisciplinary approach. METHODS A systematic search was conducted of the PubMed, MEDLINE, and SCOPUS databases to identify trials investigating the health effects of nutritional and psychological assessments in patients with CLD. RESULTS In dealing with the treatment of patients with CLD, an exploration of the psychological domain emerges as crucial, because psychological distress, especially depression, exerts a tangible influence on patient outcomes. Thus, the engagement of psychologists and/or psychotherapists, who might use techniques such as cognitive behavioral therapy, could enhance patients' comprehension of nutritional implications in their treatment and make them more aware of their illness. CONCLUSION The review emphasizes the relevance of both nutritional and psychological assessments in patients with CLD that could improve patient education on the pivotal role of nutrition in disease management. Randomized controlled trials evaluating the combined impact of nutritional and psychological support are recommended to further investigate this complex clinical landscape.
Collapse
Affiliation(s)
- Mario Romeo
- Hepatogastroenterology Division, Department of Precision Medicine, University of Campania "Luigi Vanvitelli," Naples 80138, Italy
| | - Marcello Dallio
- Hepatogastroenterology Division, Department of Precision Medicine, University of Campania "Luigi Vanvitelli," Naples 80138, Italy
| | - Marina Cipullo
- Hepatogastroenterology Division, Department of Precision Medicine, University of Campania "Luigi Vanvitelli," Naples 80138, Italy
| | - Annachiara Coppola
- Hepatogastroenterology Division, Department of Precision Medicine, University of Campania "Luigi Vanvitelli," Naples 80138, Italy
| | - Chiara Mazzarella
- Hepatogastroenterology Division, Department of Precision Medicine, University of Campania "Luigi Vanvitelli," Naples 80138, Italy
| | - Simone Mammone
- Hepatogastroenterology Division, Department of Precision Medicine, University of Campania "Luigi Vanvitelli," Naples 80138, Italy
| | - Giorgia Iadanza
- Hepatogastroenterology Division, Department of Precision Medicine, University of Campania "Luigi Vanvitelli," Naples 80138, Italy
| | - Carmine Napolitano
- Hepatogastroenterology Division, Department of Precision Medicine, University of Campania "Luigi Vanvitelli," Naples 80138, Italy
| | - Paolo Vaia
- Hepatogastroenterology Division, Department of Precision Medicine, University of Campania "Luigi Vanvitelli," Naples 80138, Italy
| | - Lorenzo Ventriglia
- Hepatogastroenterology Division, Department of Precision Medicine, University of Campania "Luigi Vanvitelli," Naples 80138, Italy
| | - Alessandro Federico
- Hepatogastroenterology Division, Department of Precision Medicine, University of Campania "Luigi Vanvitelli," Naples 80138, Italy
| |
Collapse
|
13
|
Ramier C, Carrat F, Beo VD, Parlati L, Lotto M, Marcellin F, Protopopescu C, Carrieri P, Bourliere M, ANRS/AFEF HEPATHER study group. Unhealthy Behaviours and All-Cause Mortality Among People With Chronic Hepatitis B, With and Without Hepatitis Delta (ANRS CO22 HEPATHER). J Viral Hepat 2025; 32:e70033. [PMID: 40448453 DOI: 10.1111/jvh.70033] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/04/2025] [Accepted: 05/05/2025] [Indexed: 06/02/2025]
Abstract
People infected with both hepatitis B virus (HBV) and hepatitis Delta virus (HDV) face a higher mortality risk than those mono-infected with HBV. As unhealthy behaviours can influence liver disease progression, we compared the effects of various behavioural factors on all-cause mortality among people with chronic hepatitis B (CHB), with or without chronic hepatitis Delta (CHD). We used 5-year follow-up data from people with CHB participating in the French ANRS CO22 HEPATHER cohort. A Cox proportional hazards model helped determine whether the pattern of risk factors for all-cause mortality differed according to CHD status. Of the 3884 people included, 183 had CHD and 154 died during follow-up. After multivariable adjustment, daily soft drink consumption significantly increased mortality risk in people with CHD and almost reached significance in those without CHD (adjusted hazard ratio (aHR) [95% CI]: 6.09 [2.40-15.48], p < 0.001, and 1.58 [0.97-2.56], p = 0.066 respectively). Moreover, past or current unhealthy alcohol use and tobacco smoking were both associated with a higher risk of mortality in all people with CHB (1.74 [1.09-2.79], p = 0.020, and 1.61 [1.13-2.31], p = 0.009 respectively). Daily soft drink consumption significantly increased all-cause mortality in people with CHD. Unhealthy alcohol use and tobacco smoking were associated with a higher mortality risk in all people with CHB. Education about healthy eating and support for smoking cessation and alcohol reduction could greatly improve health and survival of people with CHB, with and without CHD.
Collapse
Affiliation(s)
- Clémence Ramier
- Aix Marseille Univ, INSERM, IRD, SESSTIM, Sciences Économiques & Sociales de la Santé & Traitement de l'Information Médicale, ISSPAM, Marseille, France
| | - Fabrice Carrat
- Institut Pierre Louis d'Épidémiologie et de Santé Publique, Sorbonne Université, INSERM, Paris, France
- Hôpital Saint-Antoine, Unité de Santé Publique, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France
| | - Vincent Di Beo
- Aix Marseille Univ, INSERM, IRD, SESSTIM, Sciences Économiques & Sociales de la Santé & Traitement de l'Information Médicale, ISSPAM, Marseille, France
| | - Lucia Parlati
- Département d'Hépatologie/Addictologie, Université de Paris Cité; INSERM U1016; AP-HP, Hôpital Cochin, Paris, France
| | - Marta Lotto
- Aix Marseille Univ, INSERM, IRD, SESSTIM, Sciences Économiques & Sociales de la Santé & Traitement de l'Information Médicale, ISSPAM, Marseille, France
| | - Fabienne Marcellin
- Aix Marseille Univ, INSERM, IRD, SESSTIM, Sciences Économiques & Sociales de la Santé & Traitement de l'Information Médicale, ISSPAM, Marseille, France
| | - Camelia Protopopescu
- Aix Marseille Univ, INSERM, IRD, SESSTIM, Sciences Économiques & Sociales de la Santé & Traitement de l'Information Médicale, ISSPAM, Marseille, France
| | - Patrizia Carrieri
- Aix Marseille Univ, INSERM, IRD, SESSTIM, Sciences Économiques & Sociales de la Santé & Traitement de l'Information Médicale, ISSPAM, Marseille, France
| | - Marc Bourliere
- Aix Marseille Univ, INSERM, IRD, SESSTIM, Sciences Économiques & Sociales de la Santé & Traitement de l'Information Médicale, ISSPAM, Marseille, France
- Département d'Hépatologie et gastroentérologie, Hôpital Saint Joseph, Marseille, France
| | | |
Collapse
|
14
|
De Broucker C, Asselah T. Functional Cure in a Long-term Follow-up of Children With Chronic Hepatitis B. Clin Gastroenterol Hepatol 2025; 23:1303-1305. [PMID: 39426644 DOI: 10.1016/j.cgh.2024.09.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/20/2024] [Accepted: 09/23/2024] [Indexed: 10/21/2024]
Affiliation(s)
- Chloe De Broucker
- Université de Paris, Cité CRI, INSERM UMR 1149, Department of Hepatology, Hôpital Beaujon, APHP, Clichy, France
| | - Tarik Asselah
- Université de Paris, Cité CRI, INSERM UMR 1149, Department of Hepatology, Hôpital Beaujon, APHP, Clichy, France.
| |
Collapse
|
15
|
Choi Y, Park YK, Hur W, Kim G, Bae S. D-cycloserine, a potential candidate for reducing Hepatitis B virus cccDNA in vitro. J Virol Methods 2025; 336:115172. [PMID: 40306580 DOI: 10.1016/j.jviromet.2025.115172] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2024] [Revised: 04/19/2025] [Accepted: 04/27/2025] [Indexed: 05/02/2025]
Abstract
Hepatitis B virus (HBV) is a 3.2 kb hepatotropic DNA that possesses a unique episomal DNA form known as covalently closed circular DNA (cccDNA). cccDNA is the major risk factor for persistent HBV infection and consequently causes chronic liver diseases such as hepatitis, cirrhosis, and hepatocellular carcinoma. To prevent the progression of liver disease, eradication of HBV, especially cccDNA, is essential. In this study, we established a drug screening system using artificial recombinant HBV cccDNA (rcccDNA), which is regulated by a loxP-HBV genome and CRE expression. To identify potential drugs targeting cccDNA, a total of 379 antiviral reagents were tested. Among them, several chemicals including danoprevir, L- and D-cycloserine, phenytoin sodium, amantadine, and germacrone showed a decrease in cccDNA levels. Especially, D-cycloserine diminished the secretion of HBV antigens and induced cccDNA degradation in the HBV infection system. This screening system helps to develop the therapeutic drug target to cccDNA This screening system may help develop therapeutic drugs targeting cccDNA.
Collapse
Affiliation(s)
- Yongwook Choi
- Division of Chronic Viral Disease Research, Center for Emerging Virus Research, National Institute of Infectious Diseases, National Institute of Health, Chungbuk, South Korea.
| | - Yong Kwang Park
- Division of Chronic Viral Disease Research, Center for Emerging Virus Research, National Institute of Infectious Diseases, National Institute of Health, Chungbuk, South Korea
| | - Wonhee Hur
- Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77030, USA
| | - Gahee Kim
- Division of Chronic Viral Disease Research, Center for Emerging Virus Research, National Institute of Infectious Diseases, National Institute of Health, Chungbuk, South Korea
| | - Songmee Bae
- Division of Chronic Viral Disease Research, Center for Emerging Virus Research, National Institute of Infectious Diseases, National Institute of Health, Chungbuk, South Korea
| |
Collapse
|
16
|
Maung ST, Chaiteerakij R. Scoping Review on Strategies for Safe Nucleot(s)ide Analogue Discontinuation and Optimising Functional Cure in Chronic Hepatitis B. J Viral Hepat 2025; 32:e70040. [PMID: 40478218 DOI: 10.1111/jvh.70040] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/05/2025] [Revised: 05/05/2025] [Accepted: 05/22/2025] [Indexed: 06/11/2025]
Abstract
Chronic hepatitis B (CHB) remains a global health challenge, contributing to significant morbidity and mortality. While long-term nucleos(t)ide analogue (NA) therapy effectively suppresses viral replication, achieving a functional cure remains rare. Current treatment guidelines primarily recommend indefinite therapy. However, long-term NA use poses many challenges, prompting interest in finite therapy. Recent studies suggest that carefully selected patients may safely discontinue NAs, leading to a functional cure in some cases. This review evaluates the latest evidence on NA discontinuation, highlighting key factors influencing outcomes. This review synthesises established and emerging evidence on NA discontinuation in CHB. It explores early studies that identified quantitative HBsAg (qHBsAg) as a predictor of sustained response and HBsAg seroclearance, followed by systematic reviews and meta-analyses reinforcing finite therapy as a feasible approach. Advances in predictive modelling, incorporating biomarkers, have refined patient selection for safe NA withdrawal. Additionally, this review assesses the risks associated with NA discontinuation, highlighting the importance of identifying high-risk patients for hepatic decompensation. Ethnicity-specific qHBsAg cut-offs are also discussed, recognising variations in treatment response between Asian and Caucasian populations. Finite NA therapy is emerging as a viable approach for achieving functional cure. Future strategies should integrate liver fibrosis assessment to enhance patient selection before NA discontinuation. Optimising re-treatment approaches requires balancing timing, immune response, and qHBsAg kinetics to maximise HBsAg seroclearance. Clinical perspectives on NA discontinuation remain a key research priority, necessitating standardised guidelines and improved post-NA monitoring strategies to ensure safe and effective finite therapy in CHB management.
Collapse
Affiliation(s)
- Soe Thiha Maung
- Division of Graduate Affairs, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
- Ma Har Myaing Hospital, Yangon, Myanmar
| | - Roongruedee Chaiteerakij
- Integrated Innovation and Digital Technologies Affairs, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| |
Collapse
|
17
|
Lee HL, Lee SK, Han JW, Yang H, Nam H, Sung PS, Kim HY, Lee SW, Song DS, Kwon JH, Kim CW, Bae SH, Choi JY, Yoon SK, Jang JW. Prediction of long-term HBsAg seroclearance in patients with HBeAg-negative chronic hepatitis B. JHEP Rep 2025; 7:101391. [PMID: 40524695 PMCID: PMC12167479 DOI: 10.1016/j.jhepr.2025.101391] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/08/2024] [Revised: 02/23/2025] [Accepted: 03/07/2025] [Indexed: 06/19/2025] Open
Abstract
Background & Aims Predicting the long-term HBsAg seroclearance, an ideal endpoint, is relevant for decision-making regarding antiviral therapy for patients with chronic hepatitis B (CHB). This study aimed to identify predictors and develop a prediction model for HBsAg seroclearance in patients with HBeAg-negative CHB. Methods A total of 2,032 untreated HBeAg-negative patients who underwent a 2-year baseline observation period were enrolled. Prediction models were developed using independent predictors of seroclearance, and their performance was evaluated through internal and external validation using an independent cohort of 753 patients, along with sensitivity analyses. Results The estimated annual incidence of HBsAg seroclearance was 2.22% (15,508 person-years). Hepatitis B virus DNA Level (Low-to-intermittently high-level viremia), Old age, male Sex, and hepatitis B Surface antigen level <250 IU/ml independently predicted seroclearance. Subsequently, two prediction models were developed: HepBLOSS-1 and a simplified version, HepBLOSS-2. These models demonstrated excellent performance in predicting seroclearance at 5, 10, and 15 years, with C-indices and time-dependent area under the receiver operating characteristics curve (AUROC) values of 0.81-0.89. The 10-year cumulative incidence rate in patients with scores of ≥13 in HepBLOSS-1 and those with scores of 8 in HepBLOSS-2 was over 50%. Both models underwent rigorous internal and external validation, demonstrating good predictability with time-dependent AUROCs exceeding 0.80. The predicted seroclearance rate closely aligned with the observed rate in both models. Conclusions The HepBLOSS models for HBsAg seroclearance exhibited an outstanding ability to stratify the probability of seroclearance over a 15-year period. These models hold promising potential to guide treatment decisions, aiming to achieve a functional cure in patients with CHB. Impact and implications Achieving a functional cure for chronic hepatitis B, defined as HBsAg seroclearance, is a realistic treatment endpoint, especially given the virus's lifelong persistence in hepatocytes and its significant association with improved prognosis. This study identified independent predictors of seroclearance, including HBV DNA levels, age, sex, and HBsAg levels, and developed a robust prediction model based on these factors. The models demonstrated strong predictive accuracy over a 15-year period, offering valuable guidance for clinicians in establishing treatment strategies and predicting patient prognosis.
Collapse
Affiliation(s)
- Hae Lim Lee
- Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
- The Catholic University Liver Research Center, Seoul, Republic of Korea
| | - Soon Kyu Lee
- Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
- The Catholic University Liver Research Center, Seoul, Republic of Korea
| | - Ji Won Han
- Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
- The Catholic University Liver Research Center, Seoul, Republic of Korea
| | - Hyun Yang
- Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
- The Catholic University Liver Research Center, Seoul, Republic of Korea
| | - Heechul Nam
- Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
- The Catholic University Liver Research Center, Seoul, Republic of Korea
| | - Pil Soo Sung
- Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
- The Catholic University Liver Research Center, Seoul, Republic of Korea
| | - Hee Yeon Kim
- Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
- The Catholic University Liver Research Center, Seoul, Republic of Korea
| | - Sung Won Lee
- Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
- The Catholic University Liver Research Center, Seoul, Republic of Korea
| | - Do Seon Song
- Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
- The Catholic University Liver Research Center, Seoul, Republic of Korea
| | - Jung Hyun Kwon
- Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
- The Catholic University Liver Research Center, Seoul, Republic of Korea
| | - Chang Wook Kim
- Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
- The Catholic University Liver Research Center, Seoul, Republic of Korea
| | - Si Hyun Bae
- Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
- The Catholic University Liver Research Center, Seoul, Republic of Korea
| | - Jong Young Choi
- Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
- The Catholic University Liver Research Center, Seoul, Republic of Korea
| | - Seung Kew Yoon
- Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
- The Catholic University Liver Research Center, Seoul, Republic of Korea
| | - Jeong Won Jang
- Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
- The Catholic University Liver Research Center, Seoul, Republic of Korea
| |
Collapse
|
18
|
Kim DH, Lee HW. Letter on 'Association Between Viral Replication Activity and Postoperative Recurrence of HBV-Related Hepatocellular Carcinoma'. Aliment Pharmacol Ther 2025; 62:236-237. [PMID: 40474542 DOI: 10.1111/apt.70210] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/28/2025] [Revised: 05/15/2025] [Accepted: 05/15/2025] [Indexed: 06/29/2025]
Affiliation(s)
| | - Hye Won Lee
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Korea
| |
Collapse
|
19
|
Lin M, Xie Y, Wu J, Zhang C, Shi S, Lin N, Tong X, Li Y. Review Article: Drug-Induced Liver Injury Associated With Antibody-Based Therapies in Haematologic Malignancies. Aliment Pharmacol Ther 2025. [PMID: 40566645 DOI: 10.1111/apt.70228] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/28/2025] [Revised: 03/24/2025] [Accepted: 06/01/2025] [Indexed: 06/28/2025]
Abstract
BACKGROUND Drug-induced liver injury (DILI) is a leading cause of liver damage. It is especially prevalent in haematologic malignancies, complicating treatment regimens and posing a risk for severe outcomes such as acute liver failure. Antibody-based therapies have significantly improved treatment outcomes. However, these therapies are increasingly associated with liver injury, posing challenges in clinical management. AIMS This review aims to examine the DILI associated with antibody-based therapies in haematologic malignancies, highlighting key mechanisms, risk factors, clinical management strategies, and identifying areas that require further research. METHODS We conducted a comprehensive review of the literature on DILI induced by antibody-based therapies, including monoclonal antibodies, antibody-drug conjugates, and T-cell redirecting antibodies, specifically in the context of haematologic malignancies. RESULTS DILI associated with antibody-based therapies varies from mild transaminase elevations to severe liver injury. Risk factors include pre-existing liver disease, genetic predisposition, and therapy-specific mechanisms such as immune-mediated liver damage or direct hepatotoxic effects. Current management strategies involve routine liver function monitoring, dose modifications, and therapy discontinuation in severe cases. However, standardised guidelines remain lacking. CONCLUSIONS DILI remains a major challenge in the use of antibody-based therapies for haematologic malignancies. While progress has been made in understanding risk factors and management strategies, further research is essential to optimise patient care and balance therapeutic efficacy with liver toxicity risks.
Collapse
Affiliation(s)
- Mengmeng Lin
- Department of Clinical Pharmacy, Key Laboratory of Clinical Cancer Pharmacology and Toxicology Research of Zhejiang Province, Affiliated Hangzhou First People's Hospital, School of Medicine, Westlake University, Hangzhou, China
| | - Yaping Xie
- Department of Hematology, Affiliated Hangzhou First People's Hospital, School of Medicine, Westlake University, Zhejiang, Hangzhou, China
| | - Jiahe Wu
- Department of Clinical Pharmacy, Key Laboratory of Clinical Cancer Pharmacology and Toxicology Research of Zhejiang Province, Affiliated Hangzhou First People's Hospital, School of Medicine, Westlake University, Hangzhou, China
| | - Chong Zhang
- School of Medicine, Hangzhou City University, Zhejiang, Hangzhou, China
| | - Shanshan Shi
- School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, China
| | - Nengming Lin
- Department of Clinical Pharmacy, Key Laboratory of Clinical Cancer Pharmacology and Toxicology Research of Zhejiang Province, Affiliated Hangzhou First People's Hospital, School of Medicine, Westlake University, Hangzhou, China
| | - Xiangmin Tong
- Department of Hematology, Affiliated Hangzhou First People's Hospital, School of Medicine, Westlake University, Zhejiang, Hangzhou, China
| | - Yangling Li
- Department of Clinical Pharmacy, Key Laboratory of Clinical Cancer Pharmacology and Toxicology Research of Zhejiang Province, Affiliated Hangzhou First People's Hospital, School of Medicine, Westlake University, Hangzhou, China
| |
Collapse
|
20
|
Moreau J, Chikhoune L, Poggi C, Stabler S, Letarouilly JG, Hachulla É, Launay D. Safety profile of JAK inhibitors in inflammatory or autoimmune diseases. Rev Med Interne 2025:S0248-8663(25)00651-4. [PMID: 40562664 DOI: 10.1016/j.revmed.2025.06.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2024] [Revised: 05/25/2025] [Accepted: 06/08/2025] [Indexed: 06/28/2025]
Abstract
Over the past decade, Janus kinase inhibitors (JAKi) have emerged as a promising treatment for inflammatory and autoimmune diseases. Concurrently, there has been increasing attention to their potential side effects, particularly infectious and cardiovascular risks. In this review, we outline the various adverse effects of these treatments and emphasize the importance of their prevention. First, we examine the risk of infection and the preventive measures through screening, vaccination, and prophylaxis. Subsequently, we explore the risk of developing malignant tumors, venous thromboembolism, and major cardiovascular events. Although the data are sometimes inconsistent, they indicate the existence of a subpopulation at increased risk of JAKi side effects, including patients over 65years of age, those with cardiovascular and malignancy risk factors, and smokers. Finally, we discuss the risk and prevention strategies for gastrointestinal perforation, as well as the risk of biological abnormalities, such as cytopenias, cytolysis, dyslipidemia, and elevated CPK levels.
Collapse
Affiliation(s)
- Julie Moreau
- CHU de Lille, service de médecine interne et immunologie clinique, centre de référence des maladies auto-immunes et auto-inflammatoires systémiques rares de l'adulte du Nord, Nord-Ouest, Méditerranée et Guadeloupe (CeRAINOM), 59000 Lille, France
| | - Liticia Chikhoune
- CHU de Lille, service de médecine interne et immunologie clinique, centre de référence des maladies auto-immunes et auto-inflammatoires systémiques rares de l'adulte du Nord, Nord-Ouest, Méditerranée et Guadeloupe (CeRAINOM), 59000 Lille, France
| | - Claire Poggi
- CHU de Lille, service de médecine interne et immunologie clinique, centre de référence des maladies auto-immunes et auto-inflammatoires systémiques rares de l'adulte du Nord, Nord-Ouest, Méditerranée et Guadeloupe (CeRAINOM), 59000 Lille, France
| | - Sarah Stabler
- Service des maladies infectieuses, 59000 Lille, France; Université de Lille, U1019, UMR 9017, Center for Infection and Immunity of Lille (CIIL), 59000 Lille, France
| | - Jean-Guillaume Letarouilly
- Université de Lille, CHU de Lille, FHU PRECISE, service de rhumatologie, 59000 Lille, France; U1286-INFINITE-Institute for Translational Research in Inflammation, université de Lille, 59000 Lille, France; Inserm, 59000 Lille, France
| | - Éric Hachulla
- CHU de Lille, service de médecine interne et immunologie clinique, centre de référence des maladies auto-immunes et auto-inflammatoires systémiques rares de l'adulte du Nord, Nord-Ouest, Méditerranée et Guadeloupe (CeRAINOM), 59000 Lille, France; U1286-INFINITE-Institute for Translational Research in Inflammation, université de Lille, 59000 Lille, France; Inserm, 59000 Lille, France
| | - David Launay
- CHU de Lille, service de médecine interne et immunologie clinique, centre de référence des maladies auto-immunes et auto-inflammatoires systémiques rares de l'adulte du Nord, Nord-Ouest, Méditerranée et Guadeloupe (CeRAINOM), 59000 Lille, France; U1286-INFINITE-Institute for Translational Research in Inflammation, université de Lille, 59000 Lille, France; Inserm, 59000 Lille, France.
| |
Collapse
|
21
|
Tseng TC, Huang SC, Pan MH, Liu CJ, Chen CJ, Yang WT, Tsai CH, Su TH, Yang HC, Liu CH, Chen PJ, Yang HI, Kao JH. Hepatitis B surface antigen level identifies patients with inactive chronic hepatitis B from Asia with HCC risk below surveillance threshold. Gut 2025:gutjnl-2025-334911. [PMID: 40541298 DOI: 10.1136/gutjnl-2025-334911] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/30/2025] [Accepted: 05/30/2025] [Indexed: 06/22/2025]
Abstract
BACKGROUND Chronic hepatitis B (CHB) is a major global health concern primarily due to hepatocellular carcinoma (HCC) development. OBJECTIVE This study aimed to identify patients with inactive CHB with negligible HCC risk using hepatitis B surface antigen (HBsAg) levels, which is the key to define partial HBV cure. DESIGN Data from 2674 patients with inactive CHB (non-cirrhotic, hepatitis B e antigen negative, normal alanine transaminase (ALT), HBV DNA <2000 IU/mL) in the ERADICATE-B and REVEAL-HBV cohorts were analysed. The primary endpoint was HCC development, with HBsAg levels used to identify patients with annual HCC risk <0.2%. Results were validated using the NTUH-iMD cohort. RESULTS Over a median follow-up of 26.3 years, 76 patients developed HCC. Among 989 patients with inactive CHB with HBsAg<100 IU/mL, the annual HCC incidence was 0.08% (95% CI 0.05% to 0.13%), lower than those with HBsAg≥100 IU/mL (adjusted HR 0.35, 95% CI 0.21 to 0.61). Their HCC risk was lower than the recommended threshold for HCC surveillance and was close to the risk of the general population. Even for older patients recommended for HCC surveillance, those with HBsAg levels <100 IU/mL were associated with HCC risk lower than the surveillance threshold. Moreover, patients with inactive CHB with negligible HCC risk could be identified by combining HBsAg <100 IU/mL and normal ALT levels, without the need for HBV DNA testing, as validated in the NTUH-iMD cohort. CONCLUSION Serum HBsAg levels <100 IU/mL effectively identify patients with inactive CHB with negligible HCC risk and limited viral activity, which is important in optimising surveillance strategies and defining partial HBV cure.
Collapse
Affiliation(s)
- Tai-Chung Tseng
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
- Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan
| | - Shang-Chin Huang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
- Department of Internal Medicine, National Taiwan University Hospital Bei-Hu Branch, Taipei, Taiwan
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Mei-Hung Pan
- Genomics Research Center, Academia Sinica, Taipei, Taiwan
| | - Chun-Jen Liu
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Chien-Jen Chen
- Genomics Research Center, Academia Sinica, Taipei, Taiwan
| | - Wan-Ting Yang
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Cheng-Hsueh Tsai
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Tung-Hung Su
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Hung-Chih Yang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
- Department of Microbiology, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Chen-Hua Liu
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Pei-Jer Chen
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
- Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
- Department of Microbiology, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Hwai-I Yang
- Genomics Research Center, Academia Sinica, Taipei, Taiwan
- Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Biomedical Translation Research Center, Academia Sinica, Taipei, Taiwan
- Doctoral Program of Clinical and Experimental Medicine, National Sun Yat-Sen University, Kaohsiung, Taiwan
- Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Jia-Horng Kao
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
- Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
| |
Collapse
|
22
|
Wang J, Hu T, Chi X, Wang H, Liu Y, Xie W, Han J, Qiu Q, Yu K, Huang C, Zhang J, Fu Q, Miao Q, Du Z, Zhu H, Zhang J. Unveiling the clinical spectrum of Porto-Sinusoidal Vascular Disorder (PSVD) with chronic HBV infection: insights from a retrospective Chinese cohort. Dig Liver Dis 2025:S1590-8658(25)00801-1. [PMID: 40541511 DOI: 10.1016/j.dld.2025.05.028] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/01/2025] [Revised: 05/23/2025] [Accepted: 05/26/2025] [Indexed: 06/22/2025]
Abstract
BACKGROUND Porto-Sinusoidal Vascular Disorder (PSVD) is a non-cirrhotic vascular liver disease associated with or without signs of portal hypertension (PH). Chronic hepatitis B virus (HBV) infection frequently coexists with PSVD, but its clinical impact remains unclear. This study investigates the clinical and histopathological features of PSVD with and without chronic HBV infection. METHODS Liver biopsy records of 2007 patients from Huashan Hospital, Shanghai, China (2017-2024), were reviewed, identifying 73 cases of PSVD, of which 31 had concurrent chronic HBV infection. Clinical, histological, and imaging data were analyzed from diagnosis to follow-up. A matched analysis by age and gender compared PSVD patients with and without HBV infection. RESULTS HBV prevalence among PSVD patients (43.1%) was significantly higher than in the general population (6.1%, < 0.0001). HBV-positive patients had lower nodular regenerative hyperplasia (p = 0.008) and higher nonzonal sinusoidal dilation (p = 0.068). The HBV-negative group had higher BMI and more severe PH manifestations, including varices and portosystemic collaterals (p < 0.0001). Liver enzyme levels differed significantly between groups (p < 0.05). CONCLUSION HBV-infected PSVD patients exhibit milder PH and distinct histopathological features. Routine PSVD screening is recommended in long-term HBV management.
Collapse
Affiliation(s)
- Jinyu Wang
- Department of Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, National Medical Center for Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China
| | - Tiantian Hu
- Department of Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, National Medical Center for Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China
| | - Xiangyu Chi
- Department of Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, National Medical Center for Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China
| | - Hao Wang
- Department of Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, National Medical Center for Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China
| | - Yuqi Liu
- Department of Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, National Medical Center for Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China
| | - Wentao Xie
- Department of Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, National Medical Center for Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China
| | - Jiajia Han
- Department of Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, National Medical Center for Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China
| | - Qian Qiu
- Department of Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, National Medical Center for Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China
| | - Kangkang Yu
- Department of Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, National Medical Center for Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China
| | - Chong Huang
- Department of Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, National Medical Center for Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China
| | - Jubo Zhang
- Department of Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, National Medical Center for Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China
| | - Qingchun Fu
- Department of Hepatology, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China
| | - Qi Miao
- Department of Pathology, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China
| | - Zunguo Du
- Department of Pathology, Huashan Hospital, Fudan University, Shanghai, China.
| | - Haoxiang Zhu
- Department of Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, National Medical Center for Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China.
| | - Jiming Zhang
- Department of Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, National Medical Center for Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China; Shanghai Institute of Infectious Diseases and Biosecurity, Key Laboratory of Medical Molecular Virology (MOE/MOH), Shanghai Medical College, Fudan University, Shanghai, China; Department of Infectious Diseases, Jing'An Branch of Huashan Hospital, Fudan University, Shanghai, China.
| |
Collapse
|
23
|
Chen J, Ji D, Jia J, Zhuang H, Zhang X, Wang FS, Zhang W, Dou X, Tanwandee T, Sarin SK, Maiwall R, Kumar M, Goh GBB, Ghazinyan H, Chutaputti A, Chen PJ, You H, Yu ML, George J, Omata M, Wang GQ, Lau G, APASL Viral Elimination Taskforce. Functional cure with new antiviral therapy for hepatitis B virus: a systematic review and meta-analysis. Hepatol Int 2025:10.1007/s12072-025-10823-5. [PMID: 40528088 DOI: 10.1007/s12072-025-10823-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/26/2024] [Accepted: 03/08/2025] [Indexed: 06/20/2025]
Abstract
BACKGROUND Achieving a "functional" cure for chronic hepatitis B (HBV) is primary goal for novel antiviral treatments. We sought to evaluate efficacy and safety of these novel treatments and identified emerging barriers to achieving a functional cure. APPROACH We systematically reviewed clinical trials from 2018 to 2023, identifying 244 trials from clinicaltrials.gov records on HBV. The primary outcome was functional cure rate at the end of follow-up (EOF). Secondary outcomes included changes in HBsAg levels, HBsAg loss rates, HBV DNA rebound, and adverse events. Meta-analysis was performed. RESULTS Our meta-analysis of 19 studies involving 1789 non-cirrhotic HBV patients found a minimal functional cure rate (0.0%, 95%CI 0.0-0.4%) and low HBsAg loss rates (0.9% at the end of treatment [EOT] and 0.1% at EOF). HBsAg levels declined at EOT (-0.41 log10 IU/mL, 95%CI -0.45 to -0.37, p < 0.001) but this reduction was not sustained to EOF. Virological relapse occurred in 20.5% of cases off-treatment. Although novel treatments were well-tolerated, they had higher adverse event rates (OR = 1.77, 95%CI 1.26-2.48). Challenges to achieving a functional cure include complex trial designs and unknown confounding factors. CONCLUSION Novel antiviral treatments showed limited effectiveness in achieving HBsAg loss and reduction, highlighting the need to address identified barriers in future research.
Collapse
Affiliation(s)
- Jing Chen
- School of Public Health and Primary Care, Faculty of Medicine, Chinese University of Hong Kong, Hong Kong SAR, China.
| | - Dong Ji
- Senior Department of Hepatology, Fifth Medical Center of Chinese, PLA General Hospital, Beijing, 100039, China
| | - Jidong Jia
- Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Hui Zhuang
- Department of Microbiology and Centre for Infectious Diseases, Peking University Health Science Centre, Beijing, China
| | - Xinxin Zhang
- Research Laboratory of Clinical Virology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No.197 Ruijin 2nd Road, Shanghai, 200025, China
| | - Fu-Sheng Wang
- Treatment and Research Center for Infectious Diseases, The Fifth Medical Center of PLA General Hospital, National Clinical Research Center for Infectious Diseases, Beijing, 100039, China
| | - Wenhong Zhang
- Department of Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, National Medical Center for Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, 200040, China
| | - Xiaoguang Dou
- Department of Infectious Diseases, Shengjing Hospital of China Medical University, Shenyang, 110000, China
| | - Tawesak Tanwandee
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Salaya, Thailand
| | - Shiv Kumar Sarin
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Rakhi Maiwall
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Manoj Kumar
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - George Boon-Bee Goh
- Department of Gastroenterology & Hepatology, Duke-NUS Graduate Medical School, Singapore General Hospital, Singapore, Singapore
| | - Hasmik Ghazinyan
- Gastroenterology and Hepatology Service, Yerevan Medical Scientific Center, Yerevan, Armenia
| | - Anuchit Chutaputti
- Section of Digestive and Liver Diseases, Department of Medicine, Phramongkutklao Hospital, Bangkok, Thailand
| | - Pei-Jer Chen
- Graduate Institute of Clinical Medicine, National Taiwan University, Taipei, Taiwan
| | - Hong You
- Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Ming-Lung Yu
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Center of Hepatitis Research, College of Medicine and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Jacob George
- Storr Liver Centre, The Westmead Institute for Medical Research, Westmead Hospital and University of Sydney, Sydney, NSW, Australia
| | - Masao Omata
- Yamanashi Hospitals (Central and Kita) Organization, Kofu-shi, Yamanashi, Japan
| | - Gui-Qiang Wang
- Department of Infectious Disease, Center for Liver Disease, Peking University First Hospital, Beijing, China
- Department of Infectious Disease, Peking University International Hospital, Beijing, China
| | - George Lau
- Humanity and Health Clinical Trial Center, Humanity and Health Medical Group, 9 Queen's Road Central, Central, Hong Kong SAR, China.
- Zhongshan Hospital, Fudan University, Shanghai, China.
| | | |
Collapse
|
24
|
Pinchera B, Trucillo E, D'Agostino A, Di Fusco A, Iuliano A, Ametrano L, Esposito N, Buonomo AR, Gentile I. Update on the management of HDV infection: current events and perspectives. Microb Pathog 2025; 206:107805. [PMID: 40516886 DOI: 10.1016/j.micpath.2025.107805] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2024] [Revised: 05/24/2025] [Accepted: 06/12/2025] [Indexed: 06/16/2025]
Abstract
HDV infection has long been, and continues to be, a significant challenge. Chronic liver disease related to HDV is one of the most aggressive forms of liver disease, carrying a high risk of progression to cirrhosis and decompensated liver disease. Although an estimated 12 to 72 million people worldwide have been exposed to HDV, the prevalence of HDV-related conditions is believed to be underreported, and further epidemiological studies are needed to better understand its scope. In this context, screening for anti-HDV in all HBsAg-positive individuals could help identify undiagnosed cases of HDV, regardless of known risk factors. While certain groups are at higher risk for HDV infection, more than half of individuals with HDV infection have no identifiable risk factors. Simultaneously, the risk factors for severe disease progression remain poorly defined, although persistent and/or high viral load, along with elevated cytolysis indices, appear to be linked to a more severe disease prognosis. Once HDV infection is diagnosed, treatment becomes necessary, especially given the limited therapeutic options available. Until recently, interferon-α was the only treatment option, but it came with challenges, including poor tolerability and suboptimal virological response rates. In July 2020, the European Medicines Agency (EMA) approved Bulevirtide, a new drug for the treatment of HDV. Bulevirtide not only offered a novel therapeutic option for HDV but also marked a milestone in the history of HDV treatment. However, while this new drug represents a significant advance, there are still several aspects that need further clarification and exploration.
Collapse
Affiliation(s)
- Biagio Pinchera
- Division of Infectious Diseases, Department of Clinical Medicine and Surgery, University of Naples "Federico II", Naples, Italy.
| | - Emilia Trucillo
- Division of Infectious Diseases, Department of Clinical Medicine and Surgery, University of Naples "Federico II", Naples, Italy
| | - Alessia D'Agostino
- Division of Infectious Diseases, Department of Clinical Medicine and Surgery, University of Naples "Federico II", Naples, Italy
| | - Antonio Di Fusco
- Division of Infectious Diseases, Department of Clinical Medicine and Surgery, University of Naples "Federico II", Naples, Italy
| | - Antonio Iuliano
- Division of Infectious Diseases, Department of Clinical Medicine and Surgery, University of Naples "Federico II", Naples, Italy
| | - Luigi Ametrano
- Division of Infectious Diseases, Department of Clinical Medicine and Surgery, University of Naples "Federico II", Naples, Italy
| | - Nunzia Esposito
- Division of Infectious Diseases, Department of Clinical Medicine and Surgery, University of Naples "Federico II", Naples, Italy
| | - Antonio Riccardo Buonomo
- Division of Infectious Diseases, Department of Clinical Medicine and Surgery, University of Naples "Federico II", Naples, Italy
| | - Ivan Gentile
- Division of Infectious Diseases, Department of Clinical Medicine and Surgery, University of Naples "Federico II", Naples, Italy
| |
Collapse
|
25
|
Wang L, Ma S, Malhi LR, Wu X, Liu L, Wan X, Zhang Y, Li X, Ge S. Improvement in renal function after switching from entecavir to tenofovir alafenamide in chronic hepatitis B patients with low estimated glomerular filtration rates. Ann Hepatol 2025:101925. [PMID: 40513882 DOI: 10.1016/j.aohep.2025.101925] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/10/2024] [Revised: 03/16/2025] [Accepted: 04/06/2025] [Indexed: 06/16/2025]
Abstract
INTRODUCTION AND OBJECTIVES Tenofovir alafenamide (TAF) and entecavir (ETV) are both considered renal-friendly nucleoside/nucleotide analogs (NAs). However, the difference between ETV and TAF in terms of renal function remains unclear. This study aims to compare the renal safety profiles of two antiviral medications directly and evaluate the impact of switching from ETV to TAF treatment on renal function in chronic hepatitis B (CHB) patients with low estimated glomerular filtration rates (eGFR). PATIENTS AND METHODS A total of 179 CHB patients who received TAF (n=84) or ETV (n = 95) between 2019 and 2023 were included in the study. Changes in eGFR levels between two treatment groups from baseline to 72 weeks were compared to measure the influence of these NAs on renal function. RESULTS At baseline, 84 patients were included in each treatment group after a 1:1 propensity score matching process. At week 48, a notable different changes in eGFR were observed between the two groups. Gender, baseline eGFR, and medication (TAF/ETV) were significantly correlated with eGFR abnormalities. Furthermore, eGFR abnormalities at week 48 led to the transition of 6 patients in the ETV group to TAF. eGFR significantly increased (83.60 ± 5.45 vs. 93.39 ± 9.88 mL/min/1.73 m2; p=0.031) and serum creatinine significantly decreased (81.47±11.36 vs. 74.9±10.67 μmol/L; p=0.046) from week 48 to 60. At week 48, the incidence of low-level viremia (LLV) was 19.0% in the ETV group and 16.7% in the TAF group, respectively (p>0.05). Pairwise comparisons revealed no significant difference in the percentage of LLV between the ETV continued group and the TAF continued group at week 48, 60, and 72. Additionally, there was also no significant difference in the proportion of LLV between the ETV+TAF combination group and the TAF+ETV combination group at week 48, 60, and 72. CONCLUSIONS There was a substantial difference in eGFR between ETV and TAF treatments at week 48. Gender, baseline eGFR, and medication (TAF/ETV) were all remarkably positive indicators of eGFR abnormalities. In patients receiving ETV, an early switch to TAF may result in the reversal of early-stage renal damage.
Collapse
Affiliation(s)
- Liang Wang
- Department of Infectious Diseases, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330000, China; Key Laboratory of Liver Regenerative Medicine of Jiangxi Province. Nanchang 330000, China
| | - Shipeng Ma
- Department of Infectious Diseases, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330000, China
| | | | - Xiaoping Wu
- Department of Infectious Diseases, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330000, China; Key Laboratory of Liver Regenerative Medicine of Jiangxi Province. Nanchang 330000, China
| | - Liping Liu
- Department of Infectious Diseases, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330000, China
| | - Xin Wan
- Department of Infectious Diseases, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330000, China
| | - Yuliang Zhang
- Department of Infectious Diseases, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330000, China
| | - Xiaopeng Li
- Department of Infectious Diseases, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330000, China; Key Laboratory of Liver Regenerative Medicine of Jiangxi Province. Nanchang 330000, China
| | - Shanfei Ge
- Department of Infectious Diseases, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330000, China; Key Laboratory of Liver Regenerative Medicine of Jiangxi Province. Nanchang 330000, China.
| |
Collapse
|
26
|
Vo-Quang E, Rosse D, Ortonne V, Garrigou O, Ingiliz P, Leroy V, Pawlotsky JM, Chevaliez S. Performance of the cobas 5800 System for Hepatitis B virus DNA and Hepatitis C virus RNA quantification. Diagn Microbiol Infect Dis 2025; 112:116753. [PMID: 40031380 DOI: 10.1016/j.diagmicrobio.2025.116753] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2025] [Revised: 01/31/2025] [Accepted: 02/17/2025] [Indexed: 03/05/2025]
Abstract
Hepatitis B and C infections are an underdiagnosed global health problem. Measurement of HBV DNA or HCV RNA levels using nucleic acid-based molecular diagnostic assays has been established as the standard of care for assessing diagnosis, guiding the treatment decision, and evaluating responses to antiviral therapy. In the present study, we examined the performance of the cobas 5800 System for HBV DNA and HCV RNA quantification in a large series of patients chronically infected. Specificity of the cobas HBV and HCV Tests on the 5800 System was high (99.1 % and 100 %, respectively). Linearity using the AcroMetrix panels was excellent. Repeatability and intermediate precision coefficients of variation were within 5 %. Of the 334 clinical specimens tested in parallel on the cobas 5800 and cobas 4800 Systems for HBV and the m2000 RealTime or Alinity m Systems for HCV, only 12 (3.6 %) yielded discrepant results that were at or near the limit of quantification of the cobas 5800 assays. The correlation between viral load results was extremely high, and only weak bias were observed across the entire range of concentrations tested without clinical impact in patients who are eligible for antiviral therapy. This comparison study demonstrated equivalent performance of the new cobas 5800 System compared with other molecular platforms widely used in clinical practice for HBV DNA and HCV RNA quantification. The cobas 5800 System can be confidently used in clinical practice. A few clinical specimens with low viral loads may be missed. Further studies are warranted to confirm or refute this finding.
Collapse
Affiliation(s)
- Erwan Vo-Quang
- Department of Hepatology, Hôpital Henri Mondor, Créteil, France; Team Viruses, Hepatology, Cancer", Institut de Recherche Biomédicale, INSERM U955, Créteil, France
| | - Delphine Rosse
- French National Reference Center for Hepatitis B, C and Delta Viruses, Department of Virology, Hôpital Henri Mondor (AP-HP), Créteil, France; Team Viruses, Hepatology, Cancer", Institut de Recherche Biomédicale, INSERM U955, Créteil, France
| | - Valérie Ortonne
- French National Reference Center for Hepatitis B, C and Delta Viruses, Department of Virology, Hôpital Henri Mondor (AP-HP), Créteil, France; Team Viruses, Hepatology, Cancer", Institut de Recherche Biomédicale, INSERM U955, Créteil, France
| | - Olivia Garrigou
- French National Reference Center for Hepatitis B, C and Delta Viruses, Department of Virology, Hôpital Henri Mondor (AP-HP), Créteil, France; Team Viruses, Hepatology, Cancer", Institut de Recherche Biomédicale, INSERM U955, Créteil, France
| | - Patrick Ingiliz
- Department of Hepatology, Hôpital Henri Mondor, Créteil, France; Team Viruses, Hepatology, Cancer", Institut de Recherche Biomédicale, INSERM U955, Créteil, France
| | - Vincent Leroy
- Department of Hepatology, Hôpital Henri Mondor, Créteil, France; Team Viruses, Hepatology, Cancer", Institut de Recherche Biomédicale, INSERM U955, Créteil, France
| | - Jean-Michel Pawlotsky
- French National Reference Center for Hepatitis B, C and Delta Viruses, Department of Virology, Hôpital Henri Mondor (AP-HP), Créteil, France; Team Viruses, Hepatology, Cancer", Institut de Recherche Biomédicale, INSERM U955, Créteil, France
| | - Stéphane Chevaliez
- French National Reference Center for Hepatitis B, C and Delta Viruses, Department of Virology, Hôpital Henri Mondor (AP-HP), Créteil, France; Team Viruses, Hepatology, Cancer", Institut de Recherche Biomédicale, INSERM U955, Créteil, France.
| |
Collapse
|
27
|
Shin YE, Kim JY, Yoo JJ, Kim SG, Kim YS. Evaluating fracture risk with TDF in elderly patients with hepatitis B: A Korean perspective. J Hepatol 2025; 82:e301-e303. [PMID: 39577472 DOI: 10.1016/j.jhep.2024.11.022] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/16/2024] [Revised: 11/06/2024] [Accepted: 11/12/2024] [Indexed: 11/24/2024]
Affiliation(s)
- Yoon E Shin
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, College of Medicine, Soon Chun Hyang University, Bucheon, Republic of Korea
| | - Jae Young Kim
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, College of Medicine, Soon Chun Hyang University, Bucheon, Republic of Korea
| | - Jeong Ju Yoo
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, College of Medicine, Soon Chun Hyang University, Bucheon, Republic of Korea.
| | - Sang Gyune Kim
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, College of Medicine, Soon Chun Hyang University, Bucheon, Republic of Korea
| | - Young Seok Kim
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, College of Medicine, Soon Chun Hyang University, Bucheon, Republic of Korea
| |
Collapse
|
28
|
Degasperi E, Scholtes C, Testoni B, Renteria SU, Anolli MP, Charre C, Facchetti F, Plissonnier ML, Sambarino D, Perbellini R, Monico S, Callegaro A, García-Pras E, Lens S, Cortese MF, Forns X, Pérez-Del-Pulgar S, Heil M, Levrero M, Zoulim F, Lampertico P. Differential HBV RNA and HBcrAg patterns in untreated patients with chronic hepatitis delta. J Hepatol 2025; 82:1004-1011. [PMID: 39662705 DOI: 10.1016/j.jhep.2024.11.051] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/05/2024] [Revised: 10/02/2024] [Accepted: 11/27/2024] [Indexed: 12/13/2024]
Abstract
BACKGROUND & AIMS Serum HBV RNA and hepatitis B core-related antigen (HBcrAg) levels have been proposed as useful biomarkers in the management of patients with HBV; however, their role in chronic hepatitis delta (CHD) is currently unknown. METHODS Consecutive untreated patients with CHD were enrolled in a cross-sectional study in three EU centers. Clinical and virological characteristics were collected. Serum HBV RNA and HBcrAg levels were quantified by an automated real-time investigational assay (Cobas® 6800, Roche Diagnostics, Pleasanton, Ca, USA) and by LUMIPULSE® G HBcrAg assay (Fujirebio Europe), respectively. In 18 patients with available liver biopsies, intrahepatic analyses were performed. RESULTS Overall, 240 patients with HDV were enrolled: median age 46 years, 62% male, 53% with cirrhosis, 57% nucleos(t)ide analogue treated, median ALT 70 U/L, median HBsAg 3.8 log10 IU/ml, 88% HBeAg negative, and median HDV RNA 4.9 log10 IU/ml. HBV RNA was positive (>10 copies/ml) in only 8% of patients (median 40 [13-82,000] copies/ml), whereas HBcrAg was ≥3 log10 U/ml in 77% (median 4.2 [3.0-8.0] log10 U/ml). By combining these biomarkers, three categories were identified: 23% double negative (HBV RNA/HBcrAg), 9% double positive (HBV RNA/HBcrAg) and 68% HBV RNA negative/HBcrAg positive. HBV RNA levels positively correlated with male sex and detectable HBV DNA, while positive HBcrAg correlated with higher HBsAg levels. Double-positive patients were younger, non-European, with elevated ALT and HDV RNA levels and detectable HBV DNA. Intrahepatic HDV RNA and HBV RNA were positive in most samples, while intrahepatic levels of covalently closed circular DNA were low. CONCLUSIONS In untreated CHD, most patients had undetectable HBV RNA but quantifiable HBcrAg ("divergent pattern") in the absence of HBeAg. Additional studies aiming to unravel the molecular mechanisms underlying these findings are warranted. IMPACT AND IMPLICATIONS Serum HBV RNA and HBcrAg (hepatitis B core-related antigen) are promising biomarkers of the transcriptional activity of covalently closed circular DNA in chronic HBV infection; however, their role in patients with HBV-HDV coinfection is unknown. At variance with what is commonly observed in HBV-monoinfected patients, HBV RNA was undetectable and HBcrAg detectable in the serum of most patients with HDV ("divergent pattern"). The understanding of the viral interplay between HBV and HDV is crucial to dissect the pathogenic mechanisms associated with the distinct phenotypes of patients with HDV.
Collapse
Affiliation(s)
- Elisabetta Degasperi
- Division of Gastroenterology and Hepatology, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Caroline Scholtes
- Virology Department, Hospices Civils de Lyon (HCL) and Université Claude-Bernard Lyon 1 (UCBL1), Lyon, France; INSERM U1052, CNRS UMR-5286, Cancer Research Center of Lyon (CRCL), Lyon, France; University of Lyon, Université Claude-Bernard (UCBL), Lyon, France; The Lyon Hepatology Institute (IHU EVEREST), Lyon, France
| | - Barbara Testoni
- INSERM U1052, CNRS UMR-5286, Cancer Research Center of Lyon (CRCL), Lyon, France; University of Lyon, Université Claude-Bernard (UCBL), Lyon, France; The Lyon Hepatology Institute (IHU EVEREST), Lyon, France
| | - Sara Uceda Renteria
- Microbiology and Virology Unit, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Maria Paola Anolli
- Division of Gastroenterology and Hepatology, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Caroline Charre
- INSERM U1016, CNRS, UMR8104, Paris France; Virology Department, Hôpital Cochin, APHP, Paris France
| | - Floriana Facchetti
- Division of Gastroenterology and Hepatology, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Marie-Laure Plissonnier
- INSERM U1052, CNRS UMR-5286, Cancer Research Center of Lyon (CRCL), Lyon, France; University of Lyon, Université Claude-Bernard (UCBL), Lyon, France; The Lyon Hepatology Institute (IHU EVEREST), Lyon, France
| | - Dana Sambarino
- Division of Gastroenterology and Hepatology, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Riccardo Perbellini
- Division of Gastroenterology and Hepatology, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Sara Monico
- Division of Gastroenterology and Hepatology, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Annapaola Callegaro
- Microbiology and Virology Unit, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Ester García-Pras
- Liver Unit, Hospital Clínic, University of Barcelona, IDIBAPS, CIBEREHD, Barcelona, Spain
| | - Sabela Lens
- Liver Unit, Hospital Clínic, University of Barcelona, IDIBAPS, CIBEREHD, Barcelona, Spain
| | - Maria Francesca Cortese
- Liver unit, Group of Microbiology, Vall d'Hebron Institut de Recerca (VHIR), Vall d'Hebron Hospital Universitari, Vall d'Hebron Barcelona Hospital Campus, Universitat Autònoma de Barcelona, CIBEREHD, Barcelona, Spain
| | - Xavier Forns
- Liver Unit, Hospital Clínic, University of Barcelona, IDIBAPS, CIBEREHD, Barcelona, Spain
| | - Sofía Pérez-Del-Pulgar
- Liver Unit, Hospital Clínic, University of Barcelona, IDIBAPS, CIBEREHD, Barcelona, Spain
| | - Marintha Heil
- Roche Molecular Diagnostics, Pleasanton, California, USA
| | - Massimo Levrero
- INSERM U1052, CNRS UMR-5286, Cancer Research Center of Lyon (CRCL), Lyon, France; University of Lyon, Université Claude-Bernard (UCBL), Lyon, France; The Lyon Hepatology Institute (IHU EVEREST), Lyon, France; Department of Internal Medicine, SCIAC and the IIT Center for Life Nanoscience, Sapienza University, Rome, Italy; Hepatology Department, Hospices Civils de Lyon (HCL), France
| | - Fabien Zoulim
- INSERM U1052, CNRS UMR-5286, Cancer Research Center of Lyon (CRCL), Lyon, France; University of Lyon, Université Claude-Bernard (UCBL), Lyon, France; The Lyon Hepatology Institute (IHU EVEREST), Lyon, France; Hepatology Department, Hospices Civils de Lyon (HCL), France
| | - Pietro Lampertico
- Division of Gastroenterology and Hepatology, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy; CRC "A. M. and A. Migliavacca" Center for Liver Disease, Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy; D-SOLVE consortium, an EU Horizon Europe funded project (No 101057917), Italy.
| |
Collapse
|
29
|
Hirode G, Kilany M, Pi S, Kim A, Bhat M, Van Uum R, Lilly LB, Hansen BE, Feld JJ, Selzner N, Janssen HLA. Chronic Hepatitis B Patients Referred for Liver Transplantation After Nucleos(t)ide Analog Cessation. J Viral Hepat 2025; 32:e70031. [PMID: 40372086 PMCID: PMC12080295 DOI: 10.1111/jvh.70031] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/22/2025] [Revised: 04/22/2025] [Accepted: 04/30/2025] [Indexed: 05/16/2025]
Abstract
Nucleos(t)ide analogs (NAs) provide prolonged viral suppression with favourable clinical outcomes in chronic hepatitis B (CHB) patients. Characterisation of adverse hepatic events after NA cessation leading to liver transplantation (LT) is vital to the improvement of patient management and safety considerations. This is a retrospective case series of CHB patients who developed hepatic decompensation due to NA discontinuation and were referred for LT. Patients with hepatocellular carcinoma or coinfection were excluded. Of 11 CHB patients included (81.8% clinical jaundice, 63.6% ascites, 54.5% hepatic encephalopathy and 18.2% variceal bleeding), 45.5% underwent LT, 36.4% were waitlisted (1 active, 1 died, 2 delisted of whom 1 died), and 18.2% died after referral during the assessment period. Median age was 55.1 years, 81.8% were male, and 72.7% had cirrhosis at NA cessation. Reasons for NA withdrawal included nonadherence (81.8%) and physician discretion (18.2%). Median time from NA cessation to a decompensating event was 3.2 months, and from the decompensating event to referral was 16.0 days. This study shows that most patients experience decompensations soon after NA cessation and reinforces that patients should not discontinue treatment themselves. Physicians should very carefully select non-cirrhotic, adherent patients for NA withdrawal, after which close monitoring and timely retreatment are crucial.
Collapse
Affiliation(s)
- Grishma Hirode
- Toronto Centre for Liver Disease, Toronto General HospitalUniversity Health NetworkTorontoOntarioCanada
| | - Mai Kilany
- Toronto Centre for Liver Disease, Toronto General HospitalUniversity Health NetworkTorontoOntarioCanada
| | - Steven Pi
- Division of GastroenterologyUniversity of British ColumbiaVancouverBritish ColumbiaCanada
| | - Audrey Kim
- Multi‐Organ Transplant ProgramToronto General HospitalTorontoOntarioCanada
| | - Mamatha Bhat
- Multi‐Organ Transplant ProgramToronto General HospitalTorontoOntarioCanada
| | - Rafique Van Uum
- Toronto Centre for Liver Disease, Toronto General HospitalUniversity Health NetworkTorontoOntarioCanada
| | - Leslie B. Lilly
- Multi‐Organ Transplant ProgramToronto General HospitalTorontoOntarioCanada
| | - Bettina E. Hansen
- Toronto Centre for Liver Disease, Toronto General HospitalUniversity Health NetworkTorontoOntarioCanada
- Department of Epidemiology and BiostatisticsErasmus MC University Medical CenterRotterdamthe Netherlands
| | - Jordan J. Feld
- Toronto Centre for Liver Disease, Toronto General HospitalUniversity Health NetworkTorontoOntarioCanada
| | - Nazia Selzner
- Multi‐Organ Transplant ProgramToronto General HospitalTorontoOntarioCanada
| | - Harry L. A. Janssen
- Toronto Centre for Liver Disease, Toronto General HospitalUniversity Health NetworkTorontoOntarioCanada
- Department of Gastroenterology and HepatologyErasmus MC University Medical CenterRotterdamthe Netherlands
| |
Collapse
|
30
|
Block PD, Lim JK. Unmet needs in the clinical management of chronic hepatitis B infection. J Formos Med Assoc 2025; 124:502-507. [PMID: 39155176 DOI: 10.1016/j.jfma.2024.08.020] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2023] [Revised: 08/13/2024] [Accepted: 08/14/2024] [Indexed: 08/20/2024] Open
Abstract
The hepatitis B virus (HBV) remains a global problem despite effective tools to prevent, diagnosis, and control it. Unmet needs are identifiable across its clinical care cascade, underlining the challenges providers face in delivering effective care for patients with chronic hepatitis B. The review herein will focus on three timely clinical issues in HBV. This includes efforts to optimize delivery of perinatal HBV care, improve HBV-related hepatocellular carcinoma risk stratification models, and clarify the role of finite therapy in the HBV treatment algorithm. Important developments within these three topics will be addressed with the goal to motivate further investigation and optimization of these treatment strategies for HBV.
Collapse
Affiliation(s)
- Peter D Block
- Section of Digestive Diseases and Yale Liver Center, Yale School of Medicine, USA
| | - Joseph K Lim
- Section of Digestive Diseases and Yale Liver Center, Yale School of Medicine, USA.
| |
Collapse
|
31
|
Seremba E, Ssekitoleko R, Ocanit A, Kagimu M, Waiswa M, Nankya-Mutyoba J, Akweny E, Bakainaga A, Lawrence M, Kabugo C, Ocama P. Management of chronic hepatitis B in Uganda: A five-year experience following the initiation of a national sensitization and care campaign. J Virus Erad 2025; 11:100588. [PMID: 40182694 PMCID: PMC11964627 DOI: 10.1016/j.jve.2025.100588] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2025] [Revised: 03/03/2025] [Accepted: 03/04/2025] [Indexed: 04/05/2025] Open
Abstract
Despite having the highest Hepatitis B Virus (HBV)-related mortality globally, sub-Saharan Africa (SSA) has been slow in its disease elimination campaign. We describe a 5-year experience in HBV management at a large facility in Uganda and how it can inform future management strategies. HBV-related patient data were abstracted from clinic records. Of 2664 patients, 1828 (68.6 %) had documented chronic HBV infection. Participants were young, mean age (±SD) 31.3 (±10.6) and equally split by gender. Overall, 423 (23.1 %) were on antiviral medications including 158/229 (69.0 %) with a sonographic diagnosis of cirrhosis and 130/282 (46.1 %) with Aspartate aminotransferase to Platelet Ratio Index (APRI) score ≥0.5.48/1828 (2.6 %) had Hepatocellular Carcinoma (HCC). In multivariable analysis, APRI score ≥0.5 [OR (95 % CI) = 1.76 (1.26-2.46), p < 0.01], elevated alanine aminotransferase (ALT) [OR (95 % CI) = 2.25 (1.35-4.47), p = 0.04], and HBV viral load ≥2,000IU/mL [OR (95 % CI) = 2.97 (1.68-5.22), p < 0.01] were predictors of cirrhosis/HCC. Also, an APRI score of ≥0.5 [OR (95 % CI) = 1.62 (1.19-2.22), p = 0.01], elevated ALT [OR (95 % CI) = 2.60 (1.23-5.49), p = 0.02], cirrhosis [OR (95 % CI) = 21.65 (9.26-50.59), p < 0.01], and viral load ≥2,000IU/mL [OR (95 % CI) = 6.62 (3.93-11.15), p < 0.01] were associated with antiviral use. Cirrhosis/HCC apparently occur at lower APRI scores in SSA suggesting need for urgent adoption of the 2024 WHO guidelines which provide for earlier initiation of anti-HBV therapy.
Collapse
Affiliation(s)
- E. Seremba
- Kiruddu National Referral Hospital, Uganda
- School of Medicine, Makerere University College of Health Sciences, Kampala, Uganda
| | - R. Ssekitoleko
- School of Medicine, Makerere University College of Health Sciences, Kampala, Uganda
- World Health Organization, Uganda
| | - A. Ocanit
- Kiruddu National Referral Hospital, Uganda
- School of Medicine, Makerere University College of Health Sciences, Kampala, Uganda
| | - M.M. Kagimu
- Kiruddu National Referral Hospital, Uganda
- School of Medicine, Makerere University College of Health Sciences, Kampala, Uganda
| | - M. Waiswa
- School of Medicine, Makerere University College of Health Sciences, Kampala, Uganda
| | - J. Nankya-Mutyoba
- School of Public Health, Makerere University College of Health Sciences, Kampala, Uganda
| | - E. Akweny
- Kiruddu National Referral Hospital, Uganda
| | | | - M.R. Lawrence
- University of Virginia School of Medicine, Charlottesville, VA, United States
| | - C. Kabugo
- Kiruddu National Referral Hospital, Uganda
- School of Medicine, Makerere University College of Health Sciences, Kampala, Uganda
| | - P. Ocama
- Kiruddu National Referral Hospital, Uganda
- School of Medicine, Makerere University College of Health Sciences, Kampala, Uganda
| |
Collapse
|
32
|
van Bömmel F, Degasperi E, van Bömmel A, Facchetti F, Sambarino D, Deichsel D, Brehm J, Kamga Wouambo R, Maier M, Pfefferkorn M, Berg T, Lampertico P. Dynamics of HBV biomarkers during nucleos(t)ide analog treatment: A 14-year study. Hepatol Commun 2025; 9:e0708. [PMID: 40377494 PMCID: PMC12088637 DOI: 10.1097/hc9.0000000000000708] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/01/2024] [Accepted: 01/02/2025] [Indexed: 05/18/2025] Open
Abstract
BACKGROUND Circulating HBsAg, HBV RNA, and hepatitis B core-related antigen (HBcrAg) are potential biomarkers for the response to nucleos(t)ide analog (NA) treatment discontinuation in patients with chronic hepatitis B (CHB). We retrospectively investigated the long-term kinetics of HBsAg, HBV RNA, and HBcrAg in HBeAg-negative patients treated with NA for up to 14 years in a prospective cohort study. METHODS Ninety-six patients (mean age 65 y, 77% male, 52% with cirrhosis, all HBV genotype D) who were undergoing first (n=33, group A) or second-line (n=63, group B) treatment with tenofovir disoproxil fumarate were included. HBV biomarkers collected during tenofovir disoproxil fumarate treatment were measured in 384 serum samples stored at -20 °C. The combined biomarker endpoints associated with functional cure following NA discontinuation included HBsAg <1000 IU/mL, HBV RNA <54 copies/mL, and HBcrAg <2 log U/mL. RESULTS Before NA treatment, HBV RNA and HBcrAg were detectable in 85% (mean 3.9±2.3 [range, 0-9.2] log10 copies/mL) and 80% (mean 4.3±1.9 [2-8.9] log10 U/mL), respectively, of the patients in group A. In groups A and B, the percentages of patients with detectable HBV RNA levels decreased to 53% and 34%, respectively, during years 8-10 of NA treatment, and to 29% in group B during years 11-14 to 29%. HBcrAg could be quantified in 2% of patients in group B NA treatment years 8-10. Combined biomarker endpoints were met at baseline and at years 1-4, 5-7, 8-10, and 11-14 of treatment by 3.3%, 12% and 14%, 13% and 38%, 26% and 29%, and 41% of patients, respectively. CONCLUSIONS HBV biomarker endpoints are associated with functional cure after the discontinuation of NA increase during long-term NA treatment.
Collapse
Affiliation(s)
- Florian van Bömmel
- Department of Medicine II, Division of Hepatology, Leipzig University Medical Center, Leipzig, Germany
| | - Elisabetta Degasperi
- Division of Gastroenterology and Hepatology, Foundation IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Alena van Bömmel
- Computational Biology Group, Leibniz Institute on Aging—Fritz Lipmann Institute, Jena, Germany
| | - Floriana Facchetti
- Division of Gastroenterology and Hepatology, Foundation IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Dana Sambarino
- Division of Gastroenterology and Hepatology, Foundation IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Danilo Deichsel
- Department of Medicine II, Division of Hepatology, Leipzig University Medical Center, Leipzig, Germany
| | - Jessica Brehm
- MVZ Medizinische Labore Dessau, Dessau-Roßlau, Germany
| | - Rodrigue Kamga Wouambo
- Department of Medicine II, Division of Hepatology, Leipzig University Medical Center, Leipzig, Germany
| | - Melanie Maier
- Department of Virology, Institute of Medical Microbiology and Virology, Leipzig University Medical Center, Leipzig, Germany
| | - Maria Pfefferkorn
- Department of Medicine II, Division of Hepatology, Leipzig University Medical Center, Leipzig, Germany
| | - Thomas Berg
- Department of Medicine II, Division of Hepatology, Leipzig University Medical Center, Leipzig, Germany
| | - Pietro Lampertico
- Division of Gastroenterology and Hepatology, Foundation IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy
- Department of Pathophysiology and Transplantation, CRC “A. M. and A. Migliavacca” Center for Liver Disease, University of Milan, Milan, Italy
| |
Collapse
|
33
|
Lai JCT, Wong GLH, Tse YK, Hui VWK, Lai MSM, Chan HLY, Wong VWS, Yip TCF. Histological severity, clinical outcomes and impact of antiviral treatment in indeterminate phase of chronic hepatitis B: A systematic review and meta-analysis. J Hepatol 2025; 82:992-1003. [PMID: 39577468 DOI: 10.1016/j.jhep.2024.11.018] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/29/2024] [Revised: 11/10/2024] [Accepted: 11/13/2024] [Indexed: 11/24/2024]
Abstract
BACKGROUND & AIMS Current international guidelines recommend close monitoring and evaluation of patients with chronic hepatitis B (CHB) in the indeterminate phase, and treatment of patients at high risk of adverse outcomes. Clinical outcomes and the effect of antiviral therapy on the indeterminate phase remain unclear. We performed a systematic review and meta-analysis to study the incidence of adverse clinical outcomes including hepatocellular carcinoma (HCC), cirrhosis, and hepatic decompensation, and the effect of antiviral therapy, in the indeterminate phase. METHODS Two investigators independently searched Embase, MEDLINE, Web of Science and China National Knowledge Infrastructure from 1/1/2007 to 31/12/2023. Three investigators independently assessed study eligibility and quality. We included cohort studies and a randomised-controlled trial, allowing for calculation of the incidence rate of adverse clinical outcomes, and cross-sectional studies that reported the prevalence of moderate-to-severe inflammation and different degrees of fibrosis. Incidence rates and prevalence were pooled using generalised linear mixed-effects models and random-effects models, respectively. RESULTS One hundred and three studies (70 case-control studies [18,739 patients], 32 cohort studies [15,118 patients], and one RCT [160 patients]) were included. The annual incidence rate of HCC in patients in the indeterminate phase was 0.32% (95% CI 0.21-0.48%, I2 = 85.7%), and those of cirrhosis and hepatic decompensation were 0.67% (95% CI 0.30-1.49%, I2 = 94.3%) and 0.34% (95% CI 0.17-0.69%, I2 = 51.8%), respectively. The pooled prevalence of moderate-to-severe liver inflammation, significant fibrosis, advanced fibrosis, and cirrhosis was 40.7%, 39.7%, 17.9%, and 7.2%, respectively. Use of antiviral therapy was associated with a lower risk of HCC in patients in the indeterminate phase (adjusted incidence rate ratio 0.38, 95% CI 0.18-0.79, p = 0.009). CONCLUSIONS Patients in the indeterminate phase are at risk of developing advanced liver disease and HCC. Although inherent heterogeneity across studies limited the evidence to support expanding treatment to all patients in the indeterminate phase, antiviral therapy may reduce the risk of HCC development in high-risk subgroups. IMPACT AND IMPLICATIONS Current international guidelines recommend close monitoring and evaluation of patients with chronic hepatitis B (CHB) in the indeterminate phase, in whom antiviral treatment is not always indicated. Based on the systematic review and meta-analysis with significant heterogeneity across studies, patients in the indeterminate phase are at risk of developing hepatocellular carcinoma, cirrhosis, and hepatic decompensation. Meta-regression findings on platelet count, positive HBeAg, and age highlighted the importance of liver fibrosis assessment, accurate phase classification, and timely detection of phase transition to identify antiviral treatment indications, supporting current guideline recommendations. Antiviral treatment may reduce the risk of hepatocellular carcinoma in the high-risk subgroups of patients in the indeterminate phase. PROSPERO REGISTRATION NUMBER CRD42024537095.
Collapse
Affiliation(s)
- Jimmy Che-To Lai
- Medical Data Analytics Centre, The Chinese University of Hong Kong, Hong Kong Special Administrative Region of China; Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong Special Administrative Region of China; State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong Special Administrative Region of China; Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong Special Administrative Region of China
| | - Grace Lai-Hung Wong
- Medical Data Analytics Centre, The Chinese University of Hong Kong, Hong Kong Special Administrative Region of China; Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong Special Administrative Region of China; State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong Special Administrative Region of China
| | - Yee-Kit Tse
- Medical Data Analytics Centre, The Chinese University of Hong Kong, Hong Kong Special Administrative Region of China; Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong Special Administrative Region of China; State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong Special Administrative Region of China
| | - Vicki Wing-Ki Hui
- Medical Data Analytics Centre, The Chinese University of Hong Kong, Hong Kong Special Administrative Region of China; Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong Special Administrative Region of China; State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong Special Administrative Region of China
| | - Mandy Sze-Man Lai
- Medical Data Analytics Centre, The Chinese University of Hong Kong, Hong Kong Special Administrative Region of China; Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong Special Administrative Region of China
| | - Henry Lik-Yuen Chan
- Medical Data Analytics Centre, The Chinese University of Hong Kong, Hong Kong Special Administrative Region of China; Department of Internal Medicine, Union Hospital, Hong Kong Special Administrative Region of China
| | - Vincent Wai-Sun Wong
- Medical Data Analytics Centre, The Chinese University of Hong Kong, Hong Kong Special Administrative Region of China; Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong Special Administrative Region of China; State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong Special Administrative Region of China
| | - Terry Cheuk-Fung Yip
- Medical Data Analytics Centre, The Chinese University of Hong Kong, Hong Kong Special Administrative Region of China; Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong Special Administrative Region of China; State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong Special Administrative Region of China; Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong Special Administrative Region of China.
| |
Collapse
|
34
|
Ogawa E, Enomoto M. Blowin' in the Wind: Air Pollution and the Risk of Hepatocellular Carcinoma. Liver Int 2025; 45:e16171. [PMID: 40423520 DOI: 10.1111/liv.16171] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/27/2024] [Accepted: 11/04/2024] [Indexed: 05/28/2025]
Affiliation(s)
- Eiichi Ogawa
- Department of General Internal Medicine, Kyushu University Hospital, Fukuoka, Japan
| | - Masaru Enomoto
- Department of Hepatology, Osaka Metropolitan University Hospital, Osaka, Japan
| |
Collapse
|
35
|
Yang S. Letter: Association Between Viral Replication Activity and Postoperative Recurrence of HBV-Related Hepatocellular Carcinoma. Aliment Pharmacol Ther 2025; 61:1973-1974. [PMID: 40205956 DOI: 10.1111/apt.70136] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/21/2025] [Revised: 03/30/2025] [Accepted: 03/30/2025] [Indexed: 04/11/2025]
Affiliation(s)
- Sifu Yang
- Cancer Center, Department of Medical Oncology, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hang Zhou, Zhejiang, China
| |
Collapse
|
36
|
Wen X, Liu M, Fan Y, Xu J, Wang Z, Mao L, Gu W, Shi X, Xu J. Depalmitoylase ABHD16A negatively regulates the anti-hepatitis B virus activity of IFITM1. Microbiol Spectr 2025:e0309524. [PMID: 40434075 DOI: 10.1128/spectrum.03095-24] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2024] [Accepted: 04/25/2025] [Indexed: 05/29/2025] Open
Abstract
Interferon-inducible transmembrane (IFITM) proteins have been widely reported as antiviral factors against various viral pathogens. However, the mechanisms of IFITM regulation on hepatitis B virus (HBV), which induces chronic infection resulting in cirrhosis as well as liver cancer, remain poorly characterized. In the present study, we identified that HBV infection significantly increased the expression of IFITM1. To dissect the role of IFITM1 in HBV infection, we overexpressed IFITM1 in HepG2.215 cells and revealed that the replication of HBV was restricted by IFITM1. Recently, we demonstrated that the anti-RNA virus activity of IFITM proteins depends on palmitoylation modification, and the depalmitoylase α/β-hydrolase domain-containing 16A (ABHD16A) negatively regulates IFITM1 against RNA virus infection in human and porcine cells. However, whether ABHD16A-IFITM1 regulates DNA virus infection has not been researched. Here, by using co-immunoprecipitation (Co-IP) and acyl-PEGyl exchange gel-shift assay, ABHD16A-catalyzed depalmitoylation of IFITM1 was verified in HepG2.215 cells. In addition, we respectively knocked out IFITM1 and ABHD16A via CRISPR/Cas9 and showed that the anti-HBV activity of IFITM1 was negatively regulated by ABHD16A through depalmitoylation. Collectively, our findings demonstrated for the first time that ABHD16A catalyzes the depalmitoylation of IFITM1 to regulate its antiviral activity against HBV, which expands the biological functions of ABHD16A in immune regulation and provides potential targets for HBV infection-related disease therapy.IMPORTANCENowadays, hepatitis B virus (HBV) infection remains a major global public health problem, with over 375 million people worldwide having been infected. Chronic HBV infection leads to serious liver diseases, such as liver cirrhosis and hepatocellular carcinoma. Therefore, it is urgent to reveal the mechanism of HBV infection and uncover novel drug targets. Interferon and interferon-stimulated genes are responsible for the inhibition of HBV infection. Interferon-inducible transmembrane (IFITM) is distributed on plasma membrane, restricting various virus invasions. Nevertheless, whether and how IFITM regulates HBV infection remains unclear. Here, we show that IFITM1 inhibited the replication of HBV, which depended on palmitoylation modification. In addition, the depalmitoylase α/β-hydrolase domain-containing 16A (ABHD16A) negatively regulates the anti-HBV activity of IFITM1. Overall, our findings provided ABHD16A as a potential target for interfering with HBV replication.
Collapse
Affiliation(s)
- Xin Wen
- College of Life Science, Zhengdong New District Longzi Lake Campus, Henan Agricultural University, Zhengzhou, Henan, China
| | - Mingyang Liu
- College of Life Science, Zhengdong New District Longzi Lake Campus, Henan Agricultural University, Zhengzhou, Henan, China
| | | | - Junfei Xu
- College of Life Science, Zhengdong New District Longzi Lake Campus, Henan Agricultural University, Zhengzhou, Henan, China
| | - Zhaoyan Wang
- College of Life Science, Zhengdong New District Longzi Lake Campus, Henan Agricultural University, Zhengzhou, Henan, China
| | - Lin Mao
- College of Life Science, Zhengdong New District Longzi Lake Campus, Henan Agricultural University, Zhengzhou, Henan, China
| | - Weizhen Gu
- College of Life Science, Zhengdong New District Longzi Lake Campus, Henan Agricultural University, Zhengzhou, Henan, China
| | - Xuemeng Shi
- College of Life Science, Zhengdong New District Longzi Lake Campus, Henan Agricultural University, Zhengzhou, Henan, China
| | - Jun Xu
- College of Life Science, Zhengdong New District Longzi Lake Campus, Henan Agricultural University, Zhengzhou, Henan, China
| |
Collapse
|
37
|
Duong H, Ngo M, Dao T, Hoang T, Nguyen U, Ho T. Sensitive Detection of Plasma Fibrinogen Chain A mRNA in Hepatocellular Carcinoma Using Semi-Nested RT-PCR. Diagnostics (Basel) 2025; 15:1364. [PMID: 40506936 PMCID: PMC12155491 DOI: 10.3390/diagnostics15111364] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2025] [Revised: 05/20/2025] [Accepted: 05/27/2025] [Indexed: 06/16/2025] Open
Abstract
Background/Objectives: Hepatocellular carcinoma (HCC) remains a major cause of cancer-related mortality, with diagnostic limitations of existing biomarkers such as alpha-fetoprotein (AFP). This study evaluates plasma Fibrinogen chain A mRNA (FGA mRNA), alone and combined with AFP, for improving HCC diagnosis. Methods: A semi-nested RT-PCR assay was developed to quantify plasma FGA mRNA in 80 HCC patients and 74 controls (57 chronic liver disease [CLD] and 17 healthy donors [HDs]). Receiver operating characteristic (ROC) analysis was used to assess diagnostic performance, and logistic regression evaluated the combined biomarker model. Results: Plasma FGA mRNA levels were significantly higher in HCC patients than in CLD and HD controls (p < 0.0001). The area under the curve (AUC) for HCC vs. the combined control group (CLD + HD) was 0.721 (95% CI: 0.643-0.790), improving to 0.866 (95% CI: 0.782-0.927) when comparing HCC to HDs alone but declining for HCC vs. CLD (AUC = 0.678, 95% CI: 0.592-0.755). Combining FGA mRNA with AFP significantly enhanced diagnostic accuracy for HCC vs. CLD (AUC = 0.859, 95% CI: 0.790-0.913), with a sensitivity of 87.50% and specificity of 71.93%. In patients with low AFP levels (<20 ng/mL), the combined model identified 68.75% of HCC cases, outperforming AFP alone. Conclusions: FGA mRNA alone provides moderate diagnostic utility but substantially improves accuracy when combined with AFP, especially in low-AFP cases. This multi-biomarker approach holds promise for improving HCC detection and warrants further validation in larger cohorts.
Collapse
Affiliation(s)
- Huy Duong
- Department of Gastroenterology and Hepatology, 103 Military Hospital, Vietnam Military Medical University, Hanoi 100000, Vietnam; (H.D.)
| | - Minh Ngo
- Department of Gastroenterology and Hepatology, 103 Military Hospital, Vietnam Military Medical University, Hanoi 100000, Vietnam; (H.D.)
- Radiology Center, 103 Military Hospital, Vietnam Military Medical University, Hanoi 100000, Vietnam
| | - Trang Dao
- Department of Genomics and Cytogenetics, Institute of Biomedicine and Pharmacy (IBP), Vietnam Military Medical University, No. 222, Phung Hung, Ha Dong, Hanoi 100000, Vietnam
| | - Trang Hoang
- Department of Genomics and Cytogenetics, Institute of Biomedicine and Pharmacy (IBP), Vietnam Military Medical University, No. 222, Phung Hung, Ha Dong, Hanoi 100000, Vietnam
| | - Ung Nguyen
- Department of Translational Clinical Research, Institute of Biomedicine and Pharmacy (IBP), Vietnam Military Medical University, Hanoi 100000, Vietnam
| | - Tho Ho
- Department of Genomics and Cytogenetics, Institute of Biomedicine and Pharmacy (IBP), Vietnam Military Medical University, No. 222, Phung Hung, Ha Dong, Hanoi 100000, Vietnam
- Department of Microbiology, 103 Military Hospital, Vietnam Military Medical University, Hanoi 100000, Vietnam
| |
Collapse
|
38
|
Praguylertluck W, Kaewdech A, Chamroonkul N, Piratvisuth T, Sripongpun P. Effect of switching from prior Nucleos(t)ide Analogue(s) to Tenofovir alafenamide on lipid profile and cardiovascular risk in patients with Chronic Hepatitis B. PLoS One 2025; 20:e0324897. [PMID: 40424405 PMCID: PMC12112372 DOI: 10.1371/journal.pone.0324897] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2025] [Accepted: 05/04/2025] [Indexed: 05/29/2025] Open
Abstract
INTRODUCTION Tenofovir alafenamide (TAF) is recommended for chronic hepatitis B (CHB) treatment in international guidelines according to its efficacy and safety. However, in phase III study, an increased LDL-c was observed in those who were switched from Tenofovir disoproxil fumarate (TDF) to TAF. Limited data exists on whether lipid profiles change only in individuals who switched to TAF from TDF or from any nucleoside/nucleotide analogues (NUC). We investigated how switching to TAF affected lipid and cardiovascular outcomes in Thai CHB patients. MATERIALS AND METHODS We conducted a prospective observational study including CHB patients who had to switch from their prior NUC to TAF according to the national reimbursement policy in late 2022. All enrolled patients had lipid tests and transient elastography (TE) done at 0 and 48-week post-switch to TAF. Demographic data, prior NUC, liver biochemistry, controlled attenuated parameter (CAP) and liver stiffness (elastic modulus; E) data measured by TE were collected. The changes in lipid, Thai cardiovascular (CV) risk score, and TE results between 0 and 48-week were compared. RESULTS A total of 110 patients who were switched to TAF and completed 48-week follow-up were analyzed. The prior NUCs were as follows: 47 Lamivudine (LAM), 22 Entecavir (ETV), and 41 TDF-based. Baseline characteristics were similar between the three groups except for underlying hypertension was more frequent and baseline total cholesterol was lower in the TDF-based group. At 48-week post-switch, the median LDL-c changes were -2.45, -5.9 and +8.8 mg/dL (p<0.001), and total cholesterol changes were -4.5, -4 and +17 mg/dL (p<0.001), in the ETV, LAM, and TDF-based group, respectively. Whereas the changes in hepatic steatosis (measured by CAP), and liver stiffness (measured by E) as well as Thai CV risk score were not significantly different. No cardiovascular events occurred during follow-up. CONCLUSION Significant increase in LDL-c and total cholesterol after switching to TAF were observed only in patients with prior TDF, but not in those with prior ETV or LAM. Careful monitoring of lipids after the switch may not be universally needed. Data regarding long-term cardiovascular outcomes are warrant.
Collapse
Affiliation(s)
| | - Apichat Kaewdech
- Gastroenterology and Hepatology Unit, Division of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Hat Yai, Thailand
| | - Naichaya Chamroonkul
- Gastroenterology and Hepatology Unit, Division of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Hat Yai, Thailand
| | - Teerha Piratvisuth
- Gastroenterology and Hepatology Unit, Division of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Hat Yai, Thailand
- NKC Institute of Gastroenterology and Hepatology, Songklanagarind Hospital, Prince of Songkla University, Hat Yai, Thailand
| | - Pimsiri Sripongpun
- Gastroenterology and Hepatology Unit, Division of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Hat Yai, Thailand
| |
Collapse
|
39
|
Yang B, Yang T, Hou C, Li Y, Wang Q. Patients with chronic hepatitis B exhibiting significant inflammation and fibrosis should pay particular attention to the status of hepatic steatosis during antiviral therapy. Virol J 2025; 22:164. [PMID: 40420107 DOI: 10.1186/s12985-025-02703-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2024] [Accepted: 03/11/2025] [Indexed: 05/28/2025] Open
Abstract
OBJECTIVE This study aims to explore the effects of various hepatic steatosis conditions on histological outcomes in patients with significant inflammation and fibrosis in chronic hepatitis B (CHB) and analyze their impact on HBV virological suppression outcomes and biochemical improvement. METHOD This retrospective study included 219 chronic hepatitis B (CHB) patients receiving nucleos(t)ide analogues therapy. Each of these patients underwent two liver biopsies. Patients were categorized into four groups based on hepatic steatosis status: sustained non-hepatic steatosis (n = 118), new-onset hepatic steatosis (n = 33), sustained hepatic steatosis (n = 37), and disappeared hepatic steatosis (n = 31). We compared the liver biochemical parameters and histological changes before and after treatment. Logistic regression analysis was performed to evaluate characteristics associated with the improvement of significant liver inflammation (G ≥ 2), significant fibrosis (S ≥ 2), and the persistence of hepatic steatosis. RESULTS After treatment, the sustained non-steatosis group exhibited the highest rate of improvement in baseline significant inflammation (75.31%), while the sustained steatosis group had the lowest (42.31%, p = 0.008). The sustained steatosis group also had the highest rate of inflammation progression (15.38%, p = 0.020) and was identified as a risk factor for inadequate baseline inflammation improvement (p = 0.006, OR = 0.244, 95% CI 0.090-0.665). In terms of baseline significant liver fibrosis improvement, the sustained non-hepatic steatosis group showed the highest improvement rate (67.14%), while the sustained hepatic steatosis group had the lowest (28.00%, p = 0.006). The new-onset steatosis group had the highest rate of liver fibrosis progression (15.00%, p = 0.027), and sustained hepatic steatosis was a risk factor for poor baseline fibrosis improvement (p = 0.001, OR = 0.180, 95% CI 0.064-0.507). Furthermore, the sustained hepatic steatosis group showed the smallest decrease in liver enzyme markers ALT, GGT, and ALP post-treatment, with reductions of 22.11% (p = 0.023), 13.86% (p = 0.003), and 1.98% (p = 0.025), respectively. Logistic regression analysis revealed that high baseline BMI and LDL-C levels were significantly associated with persistent fatty liver, with high BMI (p = 0.042, OR = 1.109, 95% CI 1.004-1.226) and high LDL-C (p < 0.001, OR = 2.570, 95% CI 1.524-4.332). CONCLUSION In CHB patients with significant inflammation and fibrosis, the persistence of hepatic steatosis during antiviral treatment may impede the improvement of inflammation and fibrosis, leading to disease progression and biochemical abnormalities.
Collapse
Affiliation(s)
- Bingqing Yang
- Center of Liver Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, China
| | - Tianyuan Yang
- Center of Liver Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, China
| | - Chenxue Hou
- Laboratory Department, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Yue Li
- Laboratory Department, Beijing Ditan Hospital, Capital Medical University, Beijing, China.
| | - Qi Wang
- Center of Liver Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, China.
| |
Collapse
|
40
|
Li W, Huang R, Wang J, Zhang B, Wang Q, Feng J, Xing T. Development and validation of a new predictive model for the immune tolerance stage of chronic HBV infection based on the liver histopathological changes. BMC Gastroenterol 2025; 25:408. [PMID: 40426052 PMCID: PMC12107786 DOI: 10.1186/s12876-025-03999-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/01/2024] [Accepted: 05/15/2025] [Indexed: 05/29/2025] Open
Abstract
OBJECTIVE To identify clinical and viral indicators for the development of a new model to accurately differentiate the stages of chronic hepatitis B virus (HBV) infection based on histopathological changes in the liver. METHODS Clinical and liver pathology data from chronic hepatitis B (CHB) patients who underwent liver biopsy were retrospectively collected. The patients were allocated into test and validation groups. The area under the receiver operating characteristic (ROC) curve (AUC) was calculated to idneitfy the optimal diagnostic value for differentiating the stages of chronic HBV infection. RESULTS A total of 118 patients and 73 patients who met the diagnostic and inclusion criteria were selected as the test group and validation group, respectively. Multivariate analysis revealed that HBeAg was independently correlated with the IT and IC stages. The cutoff value of HBeAg used to quantitatively differentiate between IT and IC was 1335 S/CO. The AUC values were 0.921 (95% confidence interval (CI): 0.836-0.971) and 0.846 (95% CI: 0.726-0.967) in the test and validation groups, respectively. A new prediction model of the IT stage was established by using three indicators, namely, HBeAg, HBsAg and HBV DNA. The AUC values were 0.923 (95% CI: 0.864-0.982, p < 0.001) and 0.89 (95% CI: 0.787-0.994, p < 0.01) in the test and validation groups, respectively, when this prediction model was used. For the new model, CMA guidelines (2019 version), EASL guidelines (2017 version) and AASLD guidelines (2018 version), the error rates in the test group were 4.65%, 11.62%, 23.26%, and 46.51%, respectively, while the errors rates in the validation group were 20.0%, 25.0%, 40.0%, and 45.0%, respectively. CONCLUSIONS High levels of HBeAg, rather than HBeAg positivity, may serve as a predictor of the IT stage. A predictive model for the immune tolerance stage was established by combining three indicators. Compared with the recommended standards from multiple current guidelines, the new prediction model has a significantly lower error rate.
Collapse
Affiliation(s)
- Wentao Li
- Taizhou Hospital of Zhejiang Province affiliated to Wenzhou Medical University, Linhai, Zhejiang Province, China
| | - Rui Huang
- Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu Province, China
| | - Jian Wang
- Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu Province, China
| | - Binhao Zhang
- Taizhou Hospital of Zhejiang Province affiliated to Wenzhou Medical University, Linhai, Zhejiang Province, China
| | | | - Jiang Feng
- Taizhou Hospital of Zhejiang Province affiliated to Wenzhou Medical University, Linhai, Zhejiang Province, China
| | - Tongjing Xing
- Taizhou Hospital of Zhejiang Province affiliated to Wenzhou Medical University, Linhai, Zhejiang Province, China.
| |
Collapse
|
41
|
Lu Y, Li T, Song L, Fan Q, Wang D, Wang P, Han Y, Zhou X. MDSCs in Chronic Liver Disease: Updates and Future Challenges. J Gastroenterol Hepatol 2025. [PMID: 40405825 DOI: 10.1111/jgh.17008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/18/2025] [Revised: 04/14/2025] [Accepted: 05/09/2025] [Indexed: 05/24/2025]
Abstract
Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of pathologically expanded immature myeloid cells originating from bone marrow precursors, characterized by their potent immunosuppressive activity through mechanisms such as T cell inhibition, cytokine dysregulation, and metabolic interference. These cells are critically implicated in diverse pathological contexts, including cancer progression, chronic infections, and inflammatory disorders. In chronic liver diseases, MDSCs contribute to the pathogenesis of multiple conditions, such as chronic viral hepatitis, alcoholic liver disease (ALD), nonalcoholic fatty liver disease (NAFLD), and autoimmune liver diseases (AILD). Emerging evidence highlights their dual roles in both exacerbating tissue injury and modulating immune responses, positioning MDSCs as pivotal regulators of disease progression and potential therapeutic targets. In this review, we summarize the biological roles of MDSCs in a variety of chronic inflammatory liver diseases and explore the therapeutic potential of targeting these diseases to provide new insight for the treatment of chronic liver diseases.
Collapse
Affiliation(s)
- Yi Lu
- Shaanxi University of Chinese Medicine, Xianyang, Shaanxi, China
- Department of Digestive Diseases, Xijing Hospital of Air Force Military Medical University, Xi'an, Shaanxi, China
| | - Ting Li
- Department of Digestive Diseases, Xijing Hospital of Air Force Military Medical University, Xi'an, Shaanxi, China
| | - Liang Song
- Shaanxi University of Chinese Medicine, Xianyang, Shaanxi, China
| | - Qingling Fan
- Department of Digestive Diseases, Xijing Hospital of Air Force Military Medical University, Xi'an, Shaanxi, China
| | - Danlin Wang
- Shaanxi University of Chinese Medicine, Xianyang, Shaanxi, China
| | - Punan Wang
- Department of Digestive Diseases, Xijing Hospital of Air Force Military Medical University, Xi'an, Shaanxi, China
| | - Ying Han
- Department of Digestive Diseases, Xijing Hospital of Air Force Military Medical University, Xi'an, Shaanxi, China
| | - Xinmin Zhou
- Department of Digestive Diseases, Xijing Hospital of Air Force Military Medical University, Xi'an, Shaanxi, China
| |
Collapse
|
42
|
Jin C, Hu B, Liu H, Wang R, Jang J, Su M. Cystathionine gamma-lyase as an inflammatory factor and its link with immune inflammation in hepatitis B virus-related liver disease. Sci Rep 2025; 15:17777. [PMID: 40404804 PMCID: PMC12098708 DOI: 10.1038/s41598-025-98922-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2024] [Accepted: 04/15/2025] [Indexed: 05/24/2025] Open
Abstract
We aimed to explore the effectiveness of CTH as a serum inflammation biomarker for HCC. Enzyme-linked immunosorbent assay was used to detect serum levels of CTH, interleukin-6 (IL-6), C-reactive protein (CRP), and IL-10. The Scheuer scoring system was used to assess the liver inflammation grading (significant liver inflammation: ≥ G2 grade). CTH levels in the HCC group were significantly elevated (P < 0.0001). Of 146 patients, 58.22% exhibited significant liver inflammation. CTH levels in patients with significant liver inflammation were significantly higher than those in patients with no or mild liver inflammation (< G 2) (p < 0.0001). The area under the Receiver Operating Characteristic (ROC) curve for CTH in predicting significant hepatitis was 0.77 (sensitivity, 81.2%; specificity,62.3%). There was a significant positive correlation (r = 0.50, p < 0.05) between serum CTH levels and histopathological parameter G. The area under the ROC curve for CTH in predicting hepatocellular carcinoma was 0.83 (sensitivity, 64.6%; specificity, 83.3%). CTH and AFP improved the diagnostic accuracy of HCC. CTH levels significantly decreased 6 months post-operation (p < 0.05). The recurrence of HCC caused significant increases in CTH levels. Thus, CTH can serve as a serum inflammation marker for HCC.
Collapse
Affiliation(s)
- Chao Jin
- Infectious Diseases Department, The First Affiliated Hospital of Guangxi Medical University, Shuangyong Road, Nanning, 530021, China
| | - Bobin Hu
- Infectious Diseases Department, The First Affiliated Hospital of Guangxi Medical University, Shuangyong Road, Nanning, 530021, China
| | - Hongyu Liu
- Infectious Diseases Department, The First Affiliated Hospital of Guangxi Medical University, Shuangyong Road, Nanning, 530021, China
| | - Rongming Wang
- Infectious Diseases Department, The First Affiliated Hospital of Guangxi Medical University, Shuangyong Road, Nanning, 530021, China
| | - Jianning Jang
- Infectious Diseases Department, The First Affiliated Hospital of Guangxi Medical University, Shuangyong Road, Nanning, 530021, China
| | - Minghua Su
- Infectious Diseases Department, The First Affiliated Hospital of Guangxi Medical University, Shuangyong Road, Nanning, 530021, China.
| |
Collapse
|
43
|
Jian W, Yin Y, Xue J, Chen R, Feng J, Zeng J, He R, Zhou T. Hepatitis surface B antigen clearance induced by long-term tenofovir disoproxil fumarate monotherapy in chronic hepatitis B treatment: a meta-analysis and longitudinal modeling analysis. Virol J 2025; 22:158. [PMID: 40405187 PMCID: PMC12100987 DOI: 10.1186/s12985-025-02788-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2025] [Accepted: 05/12/2025] [Indexed: 05/24/2025] Open
Abstract
BACKGROUND Chronic hepatitis B (CHB) is a significant global health challenge, with tenofovir disoproxil fumarate (TDF) widely used as an effective treatment option. Despite TDF's efficacy in suppressing hepatitis B virus (HBV) DNA, it rarely achieves functional cure, requiring hepatitis B surface antigen (HBsAg) clearance or seroconversion, which are an optimal goal of CHB treatment. This study aimed to evaluate the long-term effects of TDF monotherapy on HBsAg clearance rates through a systematic review and meta-analysis, combined with a longitudinal modeling analysis to investigate HBsAg dynamics. METHODS Eligible studies published between January 1st, 2008, and September 28th, 2023, in PubMed, EMBASE, and Web of Science were included in the systematic review and meta-analysis. The longitudinal model was developed based on data from 123 subjects in a Phase III trial cohort. RESULTS Twenty-three studies were selected for meta-analysis. The summarized HBsAg clearance rate was near zero and unlikely to increase with extended treatment. The longitudinal model of HBsAg dynamic in CHB patients receiving TDF monotherapy showed a good fitting performance and extrapolation predictive ability. Model-based simulation confirmed that HBsAg clearance remained unlikely with prolonged therapy, with median HBsAg levels reducing by 21% after 168 weeks. CONCLUSIONS The consistency between meta-analysis and model simulation outcomes indicated that TDF monotherapy can achieve a limited reduction in HBsAg levels but did not result in functional cure, which reinforced the limited role of TDF monotherapy in comprehensive CHB management.
Collapse
Affiliation(s)
- Weizhe Jian
- Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Beijing, China
| | - Yalin Yin
- Xiamen Amoytop Biotech Co., LTD, Xiamen, China
| | - Junsheng Xue
- Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Beijing, China
| | - Rong Chen
- Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Beijing, China
| | | | - Jiayao Zeng
- Xiamen Amoytop Biotech Co., LTD, Xiamen, China
| | - Ruoyi He
- Xiamen Amoytop Biotech Co., LTD, Xiamen, China.
| | - Tianyan Zhou
- Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Beijing, China.
| |
Collapse
|
44
|
Huang R, Do AT, Toyoda H, Li J, Yasuda S, Tsai PC, Yeh ML, Trinh H, Chau A, Huang DQ, Ogawa E, Ito T, Kozuka R, Atsukawa M, Marciano S, Honda T, Watanabe T, Itokawa N, Preda CM, Tseng CH, Barreira A, Inoue K, Takahashi H, Uojima H, Kawashima K, Hsu YC, Marin RI, Sandra I, Ishigami M, Li J, Zhang J, Do S, Maeda M, Lee DH, Chuang WL, Dai CY, Huang JF, Huang CF, Cheung R, Buti M, Tanaka Y, Yuen MF, Enomoto M, Gadano A, Lim SG, Yu ML, Wu C, Nguyen MH. Distribution, Characteristics, and Natural History of Diverse Types of Indeterminate Chronic Hepatitis B: A REAL-B Study. Aliment Pharmacol Ther 2025. [PMID: 40395146 DOI: 10.1111/apt.70194] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/05/2025] [Revised: 03/12/2025] [Accepted: 05/05/2025] [Indexed: 05/22/2025]
Abstract
BACKGROUND AND AIMS Chronic hepatitis B (CHB) with indeterminate phase comprises a heterogeneous group of patients. We determined the prevalence of indeterminate CHB overall and characterised novel types and phase transition probabilities of novel types of indeterminate CHB. METHODS CHB patients were enrolled retrospectively from 24 centres (9 countries/regions). Indeterminate phase was defined based on the AASLD 2018 guidance. RESULTS The cohort included 8375 patients with a mean age of 45.0 ± 13.7 years, 22.5% HBeAg-positive, and median ALT and HBV DNA of 30 U/L and 4.3 ± 2.2 log10IU/mL, respectively. Of the total cohort, half (47.2%) were in the indeterminate phase; and of these, the most prevalent group among HBeAg-positive patients was Type 2 (ALT 1-2 × ULN, HBV DNA≥ 20,000 IU/mL; 12.6%), while in HBeAg-negative patients it was Type 6 (ALT CONCLUSIONS Indeterminate CHB can be classified into 10 types, with the most prevalent type being those with HBeAg-negative, HBV DNA ≥ 2000 IU/mL and ALT
Collapse
Affiliation(s)
- Rui Huang
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, California, USA
- Department of Infectious Disease, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China
- Institute of Viruses and Infectious Diseases, Nanjing University, Nanjing, China
| | - Ai-Thien Do
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, California, USA
- Digestive Health Associates of Texas, Dallas, Texas, USA
- The University of North Texas Health Science Center at Fort Worth, Fort Worth, Texas, USA
| | - Hidenori Toyoda
- Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Jie Li
- Department of Infectious Disease, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China
- Institute of Viruses and Infectious Diseases, Nanjing University, Nanjing, China
| | - Satoshi Yasuda
- Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Pei-Chien Tsai
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Ming-Lun Yeh
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Hepatitis Research Center, College of Medicine and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Huy Trinh
- San Jose Gastroenterology, San Jose, California, USA
| | - Angela Chau
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, California, USA
- Weill Cornell Medical College, New York, New York, USA
| | - Daniel Q Huang
- Division of Gastroenterology and Hepatology, National University Hospital, Singapore, Singapore
- Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Eiichi Ogawa
- Department of General Internal Medicine, Kyushu University Hospital, Fukuoka, Japan
| | - Takanori Ito
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Ritsuzo Kozuka
- Department of Hepatology, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan
| | - Masanori Atsukawa
- Division of Gastroenterology and Hepatology, Nippon Medical School, Tokyo, Japan
| | | | - Takashi Honda
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Tsunamasa Watanabe
- Division of Gastroenterology and Hepatology, St. Marianna University School of Medicine, Kawasaki, Japan
| | - Norio Itokawa
- Division of Gastroenterology and Hepatology, Nippon Medical School, Tokyo, Japan
| | - Carmen Monica Preda
- Department of Gastroenterology and Hepatology, Clinic Fundeni Institute, University of Medicine and Pharmacy "Carol Davila", Romania
| | - Cheng-Hao Tseng
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, E-Da Cancer Hospital/I-Shou University, Kaohsiung, Taiwan
| | - Ana Barreira
- Liver Unit, Hospital Universitari Valle D'hebron and Universitat Autònoma de Barcelona, Barcelona, and CIBEREHD del Instituto Carlos III, Spain
| | - Kaori Inoue
- Liver Center, Saga University Hospital, Saga, Japan
| | - Hirokazu Takahashi
- Liver Center, Saga University Hospital, Saga, Japan
- Division of Metabolism and Endocrinology, Faculty of Medicine, Saga University, Saga, Japan
| | - Haruki Uojima
- Department of Gastroenterology, Internal Medicine, Kitasato University School of Medicine, Sagamihara, Japan
- Genome Medical Sciences Project, Research Institute, National Center for Global Health and Medicine, Tokyo, Japan
| | | | - Yao-Chun Hsu
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, E-Da Cancer Hospital/I-Shou University, Kaohsiung, Taiwan
| | - Raluca Ioana Marin
- Department of Gastroenterology and Hepatology, Clinic Fundeni Institute, University of Medicine and Pharmacy "Carol Davila", Romania
| | - Irina Sandra
- Department of Gastroenterology and Hepatology, Clinic Fundeni Institute, University of Medicine and Pharmacy "Carol Davila", Romania
| | - Masatoshi Ishigami
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Jiayi Li
- Palo Alto Medical Foundation, Mountain View Division, Mountain View, California, USA
| | - Jian Zhang
- Chinese Hospital, San Francisco, California, USA
| | - Son Do
- The University of North Texas Health Science Center at Fort Worth, Fort Worth, Texas, USA
| | - Mayumi Maeda
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, California, USA
| | - Dong-Hyun Lee
- Division of Gastroenterology, Department of Internal Medicine, Good Gang-An Hospital, Busan, South Korea
| | - Wan-Long Chuang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Hepatitis Research Center, College of Medicine and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Chia-Yen Dai
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Hepatitis Research Center, College of Medicine and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Jee-Fu Huang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Hepatitis Research Center, College of Medicine and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Chung-Feng Huang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Hepatitis Research Center, College of Medicine and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Ramsey Cheung
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, California, USA
- Gastroenterology and Hepatology, The Palo Alto Veterans Affairs Health Care System, Palo Alto, California, USA
| | - Maria Buti
- Liver Unit, Hospital Universitari Valle D'hebron and Universitat Autònoma de Barcelona, Barcelona, and CIBEREHD del Instituto Carlos III, Spain
| | - Yasuhito Tanaka
- Department of Virology and Liver Unit, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
- Department of Gastroenterology and Hepatology, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan
| | - Man-Fung Yuen
- Department of Medicine, School of Clinical Medicine, The University of Hong Kong, Hong Kong, China
- State Key Laboratory of Liver Research, The University of Hong Kong, Hong Kong, China
| | - Masaru Enomoto
- Department of Hepatology, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan
- Department of Transfusion Medicine, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan
| | - Adrian Gadano
- Liver Unit Hospital Italiano de Buenos Aires, Buenos Aires, Argentina
| | - Seng Gee Lim
- Director of Hepatology, Division of Gastroenterology and Hepatology, National University Health System, Singapore, Singapore
| | - Ming-Lung Yu
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Hepatitis Research Center, College of Medicine and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Chao Wu
- Department of Infectious Disease, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China
- Institute of Viruses and Infectious Diseases, Nanjing University, Nanjing, China
| | - Mindie H Nguyen
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, California, USA
- Department of Epidemiology and Population Health, Stanford University, Stanford, California, USA
| |
Collapse
|
45
|
Hu Q, Zhang X, Cao X, Tao S, Chen C, Lu M, Zhao C, Chen L, Li Q, Qi X, Huang Y. Long-term effects of peginterferon-based therapy versus nucleos(t)ide analogue monotherapy in non-cirrhotic HBeAg-positive chronic hepatitis B patients. Antiviral Res 2025; 240:106192. [PMID: 40403849 DOI: 10.1016/j.antiviral.2025.106192] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2025] [Revised: 05/07/2025] [Accepted: 05/19/2025] [Indexed: 05/24/2025]
Abstract
BACKGROUND & AIMS The long-term clinical benefits of interferon (IFN)-based therapy compared to nucleos(t)ide analogue (NA) monotherapy in HBeAg-positive chronic hepatitis B (CHB) have not been well defined. This study aimed to evaluate the cumulative incidence of new-onset cirrhosis, serological responses, and hepatocellular carcinoma (HCC) development between these treatment strategies. METHODS Two independent cohorts of non-cirrhotic, HBeAg-positive CHB patients were analyzed: a treatment-naïve cohort (n = 686) and an NA-experienced cohort (n = 531). Patients received either IFN-based therapy or NA monotherapy. Propensity score matching (PSM) was employed to minimize intergroup heterogeneity. The primary endpoint was the cumulative incidence of new-onset cirrhosis. RESULTS After PSM, the 10-year cumulative incidence of new-onset cirrhosis was significantly lower in the IFN-based therapy group compared to the NA monotherapy group in both the treatment-naïve (3.3 % vs 20.0 %, p = 0.005) and NA-experienced (4.9 % vs 20.9 %, p = 0.034) cohorts. IFN-based therapy also resulted in significantly higher serological response rates across both cohorts, including HBeAg loss (treatment-naïve: 84.7 % vs 55.6 %; NA-experienced: 60.4 % vs 43.6 %, both p < 0.001) and HBsAg loss (treatment-naïve: 14.3 % vs 5.7 %, p = 0.006; NA-experienced: 10.2 % vs 1.3 %, p < 0.001). Subgroup analysis showed that patients receiving IFN-based therapy who achieved HBeAg loss within 96 weeks had the greatest long-term benefits, with lower cirrhosis incidence and higher HBsAg loss rates. Although the incidence of HCC was lower in the IFN-based group, the difference did not reach statistical significance (both p > 0.05). CONCLUSIONS IFN-based therapy provides superior long-term benefits over NA monotherapy in reducing cirrhosis risk and enhancing serological responses in HBeAg-positive CHB patients.
Collapse
Affiliation(s)
- Qiankun Hu
- Department of Liver Diseases, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China
| | - Xueyun Zhang
- Department of Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, National Medical Center for Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China
| | - Xiongyue Cao
- Department of Liver Diseases, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China
| | - Shuai Tao
- Department of Liver Diseases, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China
| | - Chong Chen
- Department of Infectious Diseases, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China
| | - Mengxin Lu
- Department of Liver Diseases, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China
| | - Conglin Zhao
- Department of Liver Diseases, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China
| | - Liang Chen
- Department of Liver Diseases, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China
| | - Qiang Li
- Department of Liver Diseases, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.
| | - Xun Qi
- Department of Liver Diseases, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.
| | - Yuxian Huang
- Department of Liver Diseases, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China; Department of Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, National Medical Center for Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China.
| |
Collapse
|
46
|
Chang LJ, Hao CQ, Rao GR, Xu LL, Li J, Cheng Y, Zheng LJ, Wu CW, Chen HX, Chen ZR, Lian JQ, Wu SH, Luo LM, Zhang WL, Zhang Y. Recurrence risk factors for chronic hepatitis B virus-infected patients who achieve functional cure with pegylated interferon-α-2b-based therapy: a multicenter pilot study. Virol J 2025; 22:146. [PMID: 40390028 PMCID: PMC12087174 DOI: 10.1186/s12985-025-02761-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2025] [Accepted: 04/25/2025] [Indexed: 05/21/2025] Open
Abstract
BACKGROUND Hepatitis B surface antigen (HBsAg) clearance is an achievable treatment endpoint for chronic hepatitis B virus (HBV)-infected patients. Pegylated interferon-α (PEG-IFN-α) induces higher rate of HBsAg clearance than nucleos(t)ide analogues. However, the influencing factors associated with HBsAg recurrence have not been fully elucidated. The aim of this study was to evaluate the risk factors for recurrence in chronic HBV-infected patients who achieved functional cure with PEG-IFN-α-2b-based treatment. METHODS A multicenter retrospective study was conducted. All patients received PEG-IFN-α-2b-based therapy, achieved HBV DNA negativity and HBsAg clearance, and were followed-up for at least 48 weeks after discontinuation of medications. The demographic data, as well as virological, serological, and biochemical indicators, were collected at baseline, therapy cessation, and during followed-up. Logistic regression analysis was subsequently performed. RESULTS A total of 101 chronic HBV-infected patients who achieved HBsAg loss with PEG-IFN-α-2b-based therapy were enrolled. The median treatment time was 24.00 (14.50, 37.50) weeks, and the median consolidation time was 11.00 (0.00, 24.00) weeks. HBsAg recurrence was found in 16 patients after a median 70.00 (48.00, 96.00) week follow-up, with a cumulative recurrence rate of 15.84%. A higher platelet count was associated with a slightly increased HBsAg recurrence risk at therapy cessation, whereas a shorter consolidation time was associated with an elevated HBsAg recurrence risk during followed-up. The appearance of anti-HBs presented a robustly reduced HBsAg recurrence risk at both therapy cessation and followed-up. No HBV DNA positivity or occurrence of end-stage liver disease was observed during treatment or followed-up. CONCLUSION The cumulative HBsAg recurrence rate was 15.84% after discontinuation of medications in chronic HBV-infected patients who achieved functional cure with PEG-IFN-α-2b-based therapy. The presence of anti-HBs reduced the HBsAg recurrence risk. CLINICAL TRIAL REGISTRATION This trial is a part of ZhuFeng Project (ClinicalTrials.gov, identifier NCT04035837) and a part of E-Cure Study (ClinicalTrials.gov, identifier NCT05182463).
Collapse
Affiliation(s)
- Li-Jun Chang
- Department of Infectious Diseases, Yuncheng Central Hospital Affiliated to Shanxi Medical University, 3690 Hedong East Rd, Yuncheng, Shanxi Province, 044000, China
| | - Chun-Qiu Hao
- Department of Infectious Diseases, Tangdu Hospital, Fourth Military Medical University, 569 Xinsi Rd, Baqiao District, Xi'an, Shaanxi Province, 710038, China
| | - Gui-Rong Rao
- Department of Central Laboratory, Air Force Hospital of Southern Theatre Command, Guangzhou, Guangdong Province, 510602, China
| | - Lin-Li Xu
- Department of Epidemiology, Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Fourth Military Medical University, 17 Changle West Rd, Xi'an, Shaanxi Province, 710032, China
| | - Jing Li
- Department of Infectious Diseases, Tangdu Hospital, Fourth Military Medical University, 569 Xinsi Rd, Baqiao District, Xi'an, Shaanxi Province, 710038, China
| | - Yan Cheng
- Department of Infectious Diseases, Tangdu Hospital, Fourth Military Medical University, 569 Xinsi Rd, Baqiao District, Xi'an, Shaanxi Province, 710038, China
| | - Li-Jun Zheng
- Department of Infectious Diseases, Yuncheng Central Hospital Affiliated to Shanxi Medical University, 3690 Hedong East Rd, Yuncheng, Shanxi Province, 044000, China
| | - Cun-Wen Wu
- Department of Infectious Diseases, Air Force Hospital of Southern Theatre Command, 801 Dongfeng East Rd, Guangzhou, Guangdong Province, 510602, China
| | - Han-Xian Chen
- Department of Infectious Diseases, Air Force Hospital of Southern Theatre Command, 801 Dongfeng East Rd, Guangzhou, Guangdong Province, 510602, China
| | - Ze-Ren Chen
- Department of Infectious Diseases, Air Force Hospital of Southern Theatre Command, 801 Dongfeng East Rd, Guangzhou, Guangdong Province, 510602, China
| | - Jian-Qi Lian
- Department of Infectious Diseases, Tangdu Hospital, Fourth Military Medical University, 569 Xinsi Rd, Baqiao District, Xi'an, Shaanxi Province, 710038, China
| | - Shi-Hong Wu
- Department of Infectious Diseases, Yuncheng Central Hospital Affiliated to Shanxi Medical University, 3690 Hedong East Rd, Yuncheng, Shanxi Province, 044000, China.
| | - Li-Min Luo
- Department of Infectious Diseases, Air Force Hospital of Southern Theatre Command, 801 Dongfeng East Rd, Guangzhou, Guangdong Province, 510602, China.
| | - Wei-Lu Zhang
- Department of Epidemiology, Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Fourth Military Medical University, 17 Changle West Rd, Xi'an, Shaanxi Province, 710032, China.
| | - Ye Zhang
- Department of Infectious Diseases, Tangdu Hospital, Fourth Military Medical University, 569 Xinsi Rd, Baqiao District, Xi'an, Shaanxi Province, 710038, China.
| |
Collapse
|
47
|
Ma HY, Yang XY, Tian YX, Li XD, He YL, Yang Q, Zheng MH, Zheng YB, Yu Y, Xu LY, Wang QN, Zhang T, Shi Y, Fan YC. Performance of the AASLD, EASL, and APASL Clinical Practice Guidelines in"grey zone"stages of Chinese patients with chronic hepatitis B. Hepatol Int 2025:10.1007/s12072-025-10833-3. [PMID: 40360826 DOI: 10.1007/s12072-025-10833-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/23/2024] [Accepted: 04/11/2025] [Indexed: 05/15/2025]
Abstract
BACKGROUND/OBJECTIVE Chronic hepatitis B (CHB) patients who do not meet any immunostaging criteria are categorized as the "grey zone" (GZ). However, there are discrepancies in the definition of the GZ in different areas. AIM To investigate the prevalence and clinical characteristics of Chinese GZ patients and to validate the application value of three international guidelines. METHODS Data from 807 naïve CHB patients with liver biopsies from seven Chinese centres were retrospectively collected. GZ patients were defined and compared across four guidelines: the Chinese guidelines, the American Association for the Study of Liver Diseases (AASLD) guidelines, the European Association for the Study of the Liver (EASL) guidelines, and the Asian Pacific Association for the Study of the Liver (APASL) guidelines. RESULTS When the Chinese guidelines were used, 38.79% of patients were categorized into the GZ, 78.91% of whom were indicated for antiviral therapy. The EASL guidelines yielded a greater proportion of GZ patients (50.56%) than did the APSAL (36.68%) and AASLD guidelines (33.21%). The APASL guidelines yielded a lower proportion of GZ patients who were indicated for antiviral therapy (42.57%) than did the AASLD (47.76%) and EASL guidelines (60.54%). According to the AASLD, EASL, APASL and Chinese guidelines, if liver biopsy was not performed, 13.06%, 31.86%, 0% and 64.54% of GZ patients were indicated for antiviral therapy, respectively. CONCLUSIONS GZ patients account for a significant proportion of CHB patients, with approximately half of them requiring antiviral therapy. CLINICAL TRIAL REGISTRATION NCT06041022.
Collapse
Affiliation(s)
- Hang-Yu Ma
- Department of Hepatology, Qilu Hospital of Shandong University, Jinan, China
| | - Xue-Yan Yang
- Department of Hepatology, Qilu Hospital of Shandong University, Jinan, China
- Department of Hepatology, The First Hospital of Lanzhou University, Lanzhou, China
| | - Yu-Xin Tian
- Department of Hepatology, Qilu Hospital of Shandong University, Jinan, China
| | - Xi-Dong Li
- Department of Infectious Diseases, Linyi People's Hospital, Linyi, China
| | - Ying-Li He
- Department of Infectious Diseases, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Qiao Yang
- Department of Infectious Diseases, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Ming-Hua Zheng
- MAFLD Research Center, Department of Hepatology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Yu-Bao Zheng
- Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Yue Yu
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Ling-Yun Xu
- Department of Infectious Diseases, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Qian-Nan Wang
- Department of Infectious Diseases, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Tao Zhang
- Department of Biostatistics, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Yu Shi
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
| | - Yu-Chen Fan
- Department of Hepatology, Qilu Hospital of Shandong University, Jinan, China.
| |
Collapse
|
48
|
Song S, Su Q, Yan Y, Ji H, Sun H, Feng K, Nuermaimaiti A, Halemubieke S, Mei L, Liu X, Lu Z, Chang L, Wang L. Identification and characteristics of mutations promoting occult HBV infection by ultrasensitive HBsAg assay. J Clin Microbiol 2025; 63:e0207124. [PMID: 40162819 PMCID: PMC12077177 DOI: 10.1128/jcm.02071-24] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2025] [Accepted: 03/11/2025] [Indexed: 04/02/2025] Open
Abstract
The significance of occult hepatitis B virus (HBV) infection (OBI) has been increasingly recognized while the underlying mechanisms remain incompletely understood. This study aimed to identify high-frequency OBI-related mutations in HBV surface antigen (HBsAg)-negative samples tested by the ultrasensitive Lumipulse G HBsAg-Quant assay. OBI samples were collected from 32 blood establishments across 14 provinces in China. Lumipulse G HBsAg-Quant assay was performed for the re-testing and reclassification of OBI. Mutations in genotypes B (GTB) and C (GTC) were analyzed to identify high-frequency single and combined mutations. Additionally, the efficacy of commercial reagents commonly employed in clinical diagnostics for detecting mutant HBsAg was evaluated. Western Blot was used for the confirmation of extracellular HBsAg as well as the detection of intracellular HBsAg. Hydrophilicity analysis and transmembrane distribution prediction of HBsAg were utilized for further validation. Single mutations at 17 sites and 9 combined mutations in GTB indicated a significantly elevated mutation frequency. In GTC, there were single mutations at 16 sites and 9 combined mutations. Several commercial reagents commonly demonstrated limited capacity toward mutant HBsAg with T123A/P, K141C, and P142R/I/K/L (GTB) and S114A/P (GTC). The findings indicated that mutations including T123A/C/K/S, S132G/Y, P142L/R/S/T, T143M, D144G, G145A, K160R+V168A, I4T+V168A, M103I+K122R, and M103I+Q181R (GTB), along with Q101H, M103I, R160K+C221Y (GTC), were associated with reduced levels of HBsAg both extracellularly and intracellularly. Additionally, K160R (GTB) and E2G (GTC) were associated with intracellular aggregation. This study elucidates the mutations associated with decreased extracellular HBsAg with ultrasensitive HBsAg assay, providing insight for further investigation into the mechanisms of OBI. IMPORTANCE The sensitivity of HBsAg detection reagents directly impacts the identification of occult hepatitis B virus (HBV) infection (OBI). This study aims to identify high-frequency OBI-related mutations in HBV surface antigen (HBsAg)-negative samples evaluated using a Fujirebio-Lumipulse ultrasensitive HBsAg assay and to investigate the implications of these mutations on the antigenicity of HBsAg, the detection capacities of various HBsAg assays, and the effects on intracellular and extracellular levels of HBsAg. Generally, our study offers a new perspective on OBI-related mutations by ultrasensitive HBsAg assay and lays the groundwork for further research on the OBI mechanism and the enhancement of HBsAg detection reagents.
Collapse
Affiliation(s)
- Shi Song
- National Center for Clinical Laboratories, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing Hospital/National Center of Gerontology, Beijing, China
- Beijing Engineering Research Center of Laboratory Medicine, Beijing Hospital, Beijing, China
- National Center for Clinical Laboratories, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China
| | - Qian Su
- National Center for Clinical Laboratories, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing Hospital/National Center of Gerontology, Beijing, China
- Beijing Engineering Research Center of Laboratory Medicine, Beijing Hospital, Beijing, China
- National Center for Clinical Laboratories, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China
| | - Ying Yan
- National Center for Clinical Laboratories, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing Hospital/National Center of Gerontology, Beijing, China
- Beijing Engineering Research Center of Laboratory Medicine, Beijing Hospital, Beijing, China
| | - Huimin Ji
- National Center for Clinical Laboratories, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing Hospital/National Center of Gerontology, Beijing, China
- Beijing Engineering Research Center of Laboratory Medicine, Beijing Hospital, Beijing, China
| | - Huizhen Sun
- National Center for Clinical Laboratories, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing Hospital/National Center of Gerontology, Beijing, China
- Beijing Engineering Research Center of Laboratory Medicine, Beijing Hospital, Beijing, China
| | - Kaihao Feng
- National Center for Clinical Laboratories, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing Hospital/National Center of Gerontology, Beijing, China
- Beijing Engineering Research Center of Laboratory Medicine, Beijing Hospital, Beijing, China
- National Center for Clinical Laboratories, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China
| | - Abudulimutailipu Nuermaimaiti
- National Center for Clinical Laboratories, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing Hospital/National Center of Gerontology, Beijing, China
- Beijing Engineering Research Center of Laboratory Medicine, Beijing Hospital, Beijing, China
- National Center for Clinical Laboratories, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China
| | - Shana Halemubieke
- National Center for Clinical Laboratories, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing Hospital/National Center of Gerontology, Beijing, China
- Beijing Engineering Research Center of Laboratory Medicine, Beijing Hospital, Beijing, China
- National Center for Clinical Laboratories, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China
| | - Ling Mei
- National Center for Clinical Laboratories, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing Hospital/National Center of Gerontology, Beijing, China
- Beijing Engineering Research Center of Laboratory Medicine, Beijing Hospital, Beijing, China
- National Center for Clinical Laboratories, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China
| | - Xinru Liu
- National Center for Clinical Laboratories, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing Hospital/National Center of Gerontology, Beijing, China
- Beijing Engineering Research Center of Laboratory Medicine, Beijing Hospital, Beijing, China
- National Center for Clinical Laboratories, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China
| | - Zhuoqun Lu
- National Center for Clinical Laboratories, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing Hospital/National Center of Gerontology, Beijing, China
- Beijing Engineering Research Center of Laboratory Medicine, Beijing Hospital, Beijing, China
| | - Le Chang
- National Center for Clinical Laboratories, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing Hospital/National Center of Gerontology, Beijing, China
- Beijing Engineering Research Center of Laboratory Medicine, Beijing Hospital, Beijing, China
- National Center for Clinical Laboratories, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China
| | - Lunan Wang
- National Center for Clinical Laboratories, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing Hospital/National Center of Gerontology, Beijing, China
- Beijing Engineering Research Center of Laboratory Medicine, Beijing Hospital, Beijing, China
- National Center for Clinical Laboratories, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China
| |
Collapse
|
49
|
Huang YJ, Wang JS, Chen CH, Chang CH, Liao SC, Lee SW, Peng YC, Lee TY, Li TC. Predictive factors and clinical outcomes in decompensated non-cirrhotic chronic hepatitis B patients treated with entecavir or tenofovir disoproxil fumarate. J Formos Med Assoc 2025:S0929-6646(25)00222-0. [PMID: 40360345 DOI: 10.1016/j.jfma.2025.05.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2024] [Revised: 04/03/2025] [Accepted: 05/08/2025] [Indexed: 05/15/2025] Open
Abstract
BACKGROUND & AIMS Little is known about the short-term and long-term outcomes of non-cirrhotic chronic hepatitis B (CHB) patients who experience hepatic decompensation. Therefore, this study aimed to investigate the clinical outcomes of decompensated non-cirrhotic CHB patients. METHODS We conducted a retrospective study and enrolled a total of 304 decompensated non-cirrhotic CHB patients. Cox regression model was used to analyze factors associated with all-cause mortality. Additionally, the incidence of HBsAg seroclearance and its associated factors were estimated by the competing risk analysis. RESULTS The median follow-up time was 4.36 years (IQR 1.04-7.16). Out of the total enrolled patients, 63 (20.72 %) patients either died or underwent liver transplantation, and 14 patients achieved HBsAg seroclearance. Risk factors associated with 1-month, 3-month, and long-term all-cause mortality were the presence of ascites and hepatic encephalopathy, baseline HBV DNA levels, and MELD scores. The cumulative incidence of HBsAg seroclearance was 1.78 %, 3.72 %, 4.25 %, 5.68 %, 5.68 %, 8.28 %, and 8.28 % at the 1-year, 2-year, 3-year, 4-year, 5-year, 6-year, and 7-year follow-up, respectively. Independent predictors for HBsAg seroclearance were baseline alanine aminotransferase (ALT)≧ 25 times upper limit of normal (subdistribution hazard ratio [sHR] = 5.97; 95 %CI, 1.82-19.63; p = 0.0032) and HBV DNA <5 log10 IU/ml (sHR = 4.43; 95 %CI, 1.55-12.63; p = 0.0054). CONCLUSIONS The presence of ascites and hepatic encephalopathy, baseline HBV DNA levels, and MELD scores were associated with short-term and long-term all-cause mortality. Additionally, lower HBV DNA levels and higher ALT levels at baseline were independently predictive of sequential HBsAg seroclearance.
Collapse
Affiliation(s)
- Yi-Jie Huang
- Department of Public Health, College of Public Health, China Medical University, Taichung, Taiwan; Department of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan; Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan
| | - Jun-Sing Wang
- Department of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan; Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung, Taiwan; Division of Endocrinology and Metabolism, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan
| | - Cheng-Hsu Chen
- Division of Nephrology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan; Department of Life Science, Tunghai University, Taichung, Taiwan
| | - Chung-Hsin Chang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan
| | - Szu-Chia Liao
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan
| | - Shou-Wu Lee
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan; Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung, Taiwan; School of Medicine, Chung Shan Medical University, Taichung, Taiwan
| | - Yen-Chun Peng
- Department of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan; Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan
| | - Teng-Yu Lee
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan; School of Medicine, Chung Shan Medical University, Taichung, Taiwan
| | - Tsai-Chung Li
- Department of Public Health, College of Public Health, China Medical University, Taichung, Taiwan; Department of Audiology and Speech-Language Pathology, College of Medical and Health Sciences, Asia University, Taichung, Taiwan.
| |
Collapse
|
50
|
Cornberg M, Sandmann L, Jaroszewicz J, Kennedy P, Lampertico P, Lemoine M, Lens S, Testoni B, Lai-Hung Wong G, Russo FP. EASL Clinical Practice Guidelines on the management of hepatitis B virus infection. J Hepatol 2025:S0168-8278(25)00174-6. [PMID: 40348683 DOI: 10.1016/j.jhep.2025.03.018] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/20/2025] [Accepted: 03/20/2025] [Indexed: 05/14/2025]
Abstract
The updated EASL Clinical Practice Guidelines on the management of hepatitis B virus (HBV) infection provide comprehensive, evidence-based recommendations for its management. Spanning ten thematic sections, the guidelines address diagnostics, treatment goals, treatment indications, therapeutic options, hepatocellular carcinoma surveillance, management of special populations, HBV reactivation prophylaxis, post-transplant care, HBV prevention strategies, and finally address open questions and future research directions. Chronic HBV remains a global health challenge, with over 250 million individuals affected and significant mortality due to cirrhosis and hepatocellular carcinoma. These guidelines emphasise the importance of early diagnosis, risk stratification based on viral and host factors, and tailored antiviral therapy. Attention is given to simplified algorithms, vaccination, and screening to support global HBV elimination targets. The guidelines also discuss emerging biomarkers and evolving definitions of functional and partial cure. Developed through literature review, expert consensus, and a Delphi process, the guidelines aim to equip healthcare providers across disciplines with practical tools to optimise HBV care and outcomes worldwide.
Collapse
|