1
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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.
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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.
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2
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Afrin N, Ciupe SM, Conway JM, Gulbudak H. Bistability between acute and chronic states in a Model of Hepatitis B Virus Dynamics. Math Biosci 2025; 387:109467. [PMID: 40456509 DOI: 10.1016/j.mbs.2025.109467] [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: 11/12/2024] [Revised: 04/22/2025] [Accepted: 05/14/2025] [Indexed: 06/16/2025]
Abstract
Understanding the mechanisms responsible for different clinical outcomes following hepatitis B infection requires a systems investigation of dynamical interactions between the virus and the immune system. To help elucidate mechanisms of protection and those responsible from transition from acute to chronic disease, we developed a deterministic mathematical model of hepatitis B infection that accounts for cytotoxic immune responses resulting in infected cell death, non-cytotoxic immune responses resulting in infected cell cure and protective immunity from reinfection, and cell proliferation. We analyzed the model and presented outcomes based on three important disease markers: the basic reproduction number R0, the infected cells death rate δ (describing the effect of cytotoxic immune responses), and the liver carrying capacity K (describing the liver susceptibility to infection). Using asymptotic and bifurcation analysis techniques, we determined regions where virus is cleared, virus persists, and where clearance-persistence is determined by the size of viral inoculum. These results can guide the development of personalized intervention.
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Affiliation(s)
- Nazia Afrin
- Department of Mathematics, University of Louisiana at Lafayette, 104 E. University Circle Lafayette, Lafayette, 70503, LA, USA
| | - Stanca M Ciupe
- Department of Mathematics and Virginia Tech Center for the Mathematics of Biosystems, Virginia Tech, Blacksburg, VA, USA
| | - Jessica M Conway
- Department of Mathematics and Center for Infectious Disease Dynamics, Pennsylvania State University, University Park, PA, USA
| | - Hayriye Gulbudak
- Department of Mathematics, University of Louisiana at Lafayette, 104 E. University Circle Lafayette, Lafayette, 70503, LA, USA.
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3
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Bhat KD, Bhattacharya H, Jayaraman Y, Kanungo S, Pattnaik M, Pati S, Bhattacharya D. Hepatitis B virus infection among children aged 1- 5 years of Mayurbhanj district (Odisha), India: A prospective study protocol. PLoS One 2025; 20:e0317621. [PMID: 40440311 PMCID: PMC12121816 DOI: 10.1371/journal.pone.0317621] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2024] [Accepted: 01/01/2025] [Indexed: 06/02/2025] Open
Abstract
BACKGROUND Over past few years, global healthcare landscape has seen an increased recognition of the significance of infectious diseases, especially those affecting vulnerable populations such as young children, one of these diseases, Hepatitis B has emerged as a notable public health concern. Hepatitis B is highly transmissible during early years of life and may lead to complications like long-term chronicity, cirrhosis of liver and the progression of hepatocellular carcinoma. To address this growing concern, there is a pressing need for community-based studies to assess the prevalence, transmission patterns, risk factors, and potential interventions for Hepatitis B among children below the age of five. These studies should also assess the community's knowledge and practices regarding Hepatitis B and immunization. METHODS The cross- sectional study will include a sample size of 2700 children aged between 1 to 5 years of Mayurbhanj district, Odisha. The serum samples will be tested for Hepatitis B surface antigen (HBsAg) and Hepatitis B surface antibody (anti-HBs). A detailed questionnaire will be prepared after focus group discussions with caregivers and healthcare workers to describe their knowledge and practices regarding HBV disease, associated risk factor and immunization. DISCUSSION The prospective sero-epidemiological study conducted within the community will assist in determining the prevalence of Hepatitis B within the vulnerable population. It will provide valuable insights for monitoring the current status of Hepatitis B in Mayurbhanj district and contribute to enhancing ongoing efforts in vaccination, control, and eradication of Hepatitis B.
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Affiliation(s)
- K. Divyasree Bhat
- Department of Microbiology & One Health, ICMR- Regional Medical Research Centre, Bhubaneswar, Odisha, India
- The Tamil Nadu Dr MGR Medical University, Chennai, Tamil Nadu, India
| | - Haimanti Bhattacharya
- Department of Microbiology & One Health, ICMR- Regional Medical Research Centre, Bhubaneswar, Odisha, India
| | | | - Srikanta Kanungo
- Department of Microbiology & One Health, ICMR- Regional Medical Research Centre, Bhubaneswar, Odisha, India
| | - Matrujyoti Pattnaik
- Department of Microbiology & One Health, ICMR- Regional Medical Research Centre, Bhubaneswar, Odisha, India
| | - Sanghamitra Pati
- Department of Microbiology & One Health, ICMR- Regional Medical Research Centre, Bhubaneswar, Odisha, India
| | - Debdutta Bhattacharya
- Department of Microbiology & One Health, ICMR- Regional Medical Research Centre, Bhubaneswar, Odisha, India
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4
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Shimizu K, Luhulla K, Msoffe M, Chambega C, Mahawi S, Ewald P, Sandi G, Msirikale I, Philbert R, Kabona R, Chirande L, Nakiddu NJ, Scanlan P, Smith C, Miyazaki Y, Maringe C, Rachet B, Mwamtemi H. Clinical characteristics and outcomes of paediatric acute lymphoblastic leukaemia in a tertiary hospital in Tanzania: a single-centre observational study. Trop Med Health 2025; 53:76. [PMID: 40426196 PMCID: PMC12107958 DOI: 10.1186/s41182-025-00760-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2025] [Accepted: 05/11/2025] [Indexed: 05/29/2025] Open
Abstract
BACKGROUND A wide inequality exists between high- and low-income countries in the outcome of paediatric acute lymphoblastic leukaemia (ALL). At a tertiary-level hospital in Tanzania, multidimensional approaches have been taken to improve cancer care for children. This study aimed to update the outcomes of paediatric ALL at Muhimbili National Hospital (MNH), Tanzania from 2016 to 2020. METHODS We performed a retrospective chart review of children who were treated with modified UKALL2003 protocol at MNH from January 1, 2016 to December 31, 2020. We used the Cox proportional hazards model to estimate the effect of each prognostic factor on event-free survival (EFS). RESULTS We identified 202 patients who had confirmatory diagnoses of ALL and initiated treatment at MNH. Fifty-two patients (26%, 52/202) died (n = 47) or abandoned treatment (n = 5) before the end of remission induction. The main causes of death during this period were infections and bleeding complications. The median EFS was 9 months and 2-year EFS was 36%. Oedema, non-early rapid responder, and non-remission were associated with short EFS in the multivariable analysis. CONCLUSIONS The number of new paediatric ALL admissions at MNH has doubled in the past decade. The prevention of early deaths is critical to improve the long-term survival of paediatric ALL in Tanzania.
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Affiliation(s)
- Koki Shimizu
- School of Tropical Medicine and Global Health, Nagasaki University, 1-12-4 Sakamoto, Nagasaki, 852-8523, Japan.
- Inequalities in Cancer Outcomes Network (ICON), Department of Health Services Research and Policy, Faculty of Public Health and Policy, London School of Hygiene and Tropical Medicine, 15-17 Tavistock Place, London, WC1H 9SH, UK.
| | - Koga Luhulla
- Department of Paediatrics and Child Health, Muhimbili National Hospital, Malik road, Dar es Salaam, P.O. Box 65000, Tanzania
| | - Magreth Msoffe
- Department of Paediatrics and Child Health, Muhimbili National Hospital, Malik road, Dar es Salaam, P.O. Box 65000, Tanzania
| | - Chambega Chambega
- Department of Paediatrics and Child Health, Muhimbili National Hospital, Malik road, Dar es Salaam, P.O. Box 65000, Tanzania
| | - Salama Mahawi
- Department of Paediatrics and Child Health, Muhimbili National Hospital, Malik road, Dar es Salaam, P.O. Box 65000, Tanzania
| | - Primus Ewald
- Department of Paediatrics and Child Health, Muhimbili National Hospital, Malik road, Dar es Salaam, P.O. Box 65000, Tanzania
| | - Godlove Sandi
- Department of Paediatrics and Child Health, Muhimbili National Hospital, Malik road, Dar es Salaam, P.O. Box 65000, Tanzania
| | - Irene Msirikale
- Department of Paediatrics and Child Health, Muhimbili University of Health and Allied Sciences, United Nations road, Dar Es Salaam, P.O. Box 65001, Tanzania
| | - Ruchius Philbert
- Department of Paediatrics and Child Health, Muhimbili National Hospital, Malik road, Dar es Salaam, P.O. Box 65000, Tanzania
| | - Regina Kabona
- Department of Paediatrics and Child Health, Muhimbili National Hospital, Malik road, Dar es Salaam, P.O. Box 65000, Tanzania
| | - Lulu Chirande
- Department of Paediatrics and Child Health, Muhimbili National Hospital, Malik road, Dar es Salaam, P.O. Box 65000, Tanzania
- Department of Paediatrics and Child Health, Muhimbili University of Health and Allied Sciences, United Nations road, Dar Es Salaam, P.O. Box 65001, Tanzania
| | - Nana Jacqueline Nakiddu
- Department of Paediatrics and Child Health, Muhimbili National Hospital, Malik road, Dar es Salaam, P.O. Box 65000, Tanzania
- Department of Paediatrics and Child Health, Muhimbili University of Health and Allied Sciences, United Nations road, Dar Es Salaam, P.O. Box 65001, Tanzania
| | - Patricia Scanlan
- Department of Paediatrics and Child Health, Muhimbili National Hospital, Malik road, Dar es Salaam, P.O. Box 65000, Tanzania
| | - Chris Smith
- School of Tropical Medicine and Global Health, Nagasaki University, 1-12-4 Sakamoto, Nagasaki, 852-8523, Japan
| | - Yasushi Miyazaki
- Department of Haematology, Atomic Bomb Disease Institute, Nagasaki University, 1-12-4 Sakamoto, Nagasaki, 852-8523, Japan
| | - Camille Maringe
- Inequalities in Cancer Outcomes Network (ICON), Department of Health Services Research and Policy, Faculty of Public Health and Policy, London School of Hygiene and Tropical Medicine, 15-17 Tavistock Place, London, WC1H 9SH, UK
| | - Bernard Rachet
- Inequalities in Cancer Outcomes Network (ICON), Department of Health Services Research and Policy, Faculty of Public Health and Policy, London School of Hygiene and Tropical Medicine, 15-17 Tavistock Place, London, WC1H 9SH, UK
| | - Hadija Mwamtemi
- Department of Paediatrics and Child Health, Muhimbili National Hospital, Malik road, Dar es Salaam, P.O. Box 65000, Tanzania
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Pavlova A, Fan Z, Lynch DL, Gumbart JC. Machine Learning of Molecular Dynamics Simulations Provides Insights into the Modulation of Viral Capsid Assembly. J Chem Inf Model 2025; 65:4844-4853. [PMID: 40338128 PMCID: PMC12117555 DOI: 10.1021/acs.jcim.5c00274] [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: 02/22/2025] [Revised: 04/13/2025] [Accepted: 04/17/2025] [Indexed: 05/09/2025]
Abstract
An effective approach in the development of novel antivirals is to target the assembly of viral capsids by using capsid assembly modulators (CAMs). CAMs targeting hepatitis B virus (HBV) have two major modes of function: they can either accelerate nucleocapsid assembly, retaining its structure, or misdirect it into noncapsid-like particles. Previous molecular dynamics (MD) simulations of early capsid-assembly intermediates showed differences in protein conformations for the apo and bound states. Here, we have developed and tested several classification machine learning (ML) models to better distinguish between apo-tetramer intermediates and those bound to accelerating or misdirecting CAMs. Models based on tertiary structural properties of the Cp149 tetramers and their interdimer orientation, as well as models based on direct and inverse contact distances between protein residues, were tested. All models distinguished the apo states and the two CAM-bound states with high accuracy. Furthermore, tertiary structure models and residue-distance models highlighted different tetramer regions as being important for classification. Both models can be used to better understand structural transitions that govern the assembly of nucleocapsids and to assist in the development of more potent CAMs. Finally, we demonstrate the utility of classification ML methods in comparing MD trajectories and describe our ML approaches, which can be extended to other systems of interest.
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Affiliation(s)
- Anna Pavlova
- School
of Physics, Georgia Institute of Technology, Atlanta, Georgia30332, United States
| | - Zixing Fan
- Interdisciplinary
Bioengineering Graduate Program, Georgia
Institute of Technology, Atlanta, Georgia30332, United States
| | - Diane L. Lynch
- School
of Physics, Georgia Institute of Technology, Atlanta, Georgia30332, United States
| | - James C. Gumbart
- School
of Physics, Georgia Institute of Technology, Atlanta, Georgia30332, United States
- School
of Chemistry & Biochemistry, Georgia
Institute of Technology, Atlanta, Georgia30332, United States
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6
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Lehtinen M, van Damme P, Beddows S, Pinto LA, Mariz F, Gray P, Dillner J. Scientific approaches to defining HPV vaccine-induced protective immunity. Int J Cancer 2025; 156:1848-1857. [PMID: 39945620 PMCID: PMC11924311 DOI: 10.1002/ijc.35345] [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: 09/16/2024] [Revised: 11/06/2024] [Accepted: 12/16/2024] [Indexed: 03/21/2025]
Abstract
Seventeen years after the licensure of prophylactic human papillomavirus (HPV) L1 virus-like-particle vaccines, a defined antibody level that correlates with vaccine-induced protection against HPV infections and associated neoplasia is missing. In contrast, correlates of protection have been defined for many viral vaccines, including for the hepatitis B virus (HBV) vaccine. This review includes lessons learned from vaccination against HBV and the use of an established protective HBV surface antigen antibody level: 10 mIU/mL, an overview of HPV infection-induced and HPV vaccine-induced antibody responses, successful efforts to establish international standardization of serological reagents and associated tools, and 15-year vigilance of HPV vaccine-induced antibody levels in a vaccination cohort against breakthrough infections. This report identifies progress but also gaps on the journey toward the definition of a HPV vaccine-induced correlate of protection.
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Affiliation(s)
- Matti Lehtinen
- Department of VaccinesInstitute for Health and WelfareHelsinkiFinland
- Center for Cervical Cancer Elimination, Department of Clinical Science, Intervention and TechnologyKarolinska InstituteStockholmSweden
| | - Pierre van Damme
- Centre for the Evaluation of Vaccination@VaccinopolisUniversiteit AntwerpAntwerpBelgium
| | - Simon Beddows
- Virus Reference Department, Public Health Microbiology DivisionUK Health Security AgencyLondonUK
| | - Ligia A. Pinto
- HPV Serology LaboratoryFrederick National Laboratory for Cancer ResearchFrederickMarylandUSA
| | - Filipe Mariz
- Division of Infections and CancerDeutsches KrebsforschungszentrumHeidelbergGermany
| | - Penelope Gray
- Center for Cervical Cancer Elimination, Department of Clinical Science, Intervention and TechnologyKarolinska InstituteStockholmSweden
| | - Joakim Dillner
- Center for Cervical Cancer Elimination, Department of Clinical Science, Intervention and TechnologyKarolinska InstituteStockholmSweden
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7
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Sebastião CS, Machado MG, Vigário J, Comandante F, Armando A, Silva MLS, Sebastião JMK, Manico E, Machado D, Pimentel V. Trends in active hepatitis B virus infection and associated risk factors among blood donor candidates from Luanda, Angola. Sci Rep 2025; 15:16478. [PMID: 40355449 PMCID: PMC12069573 DOI: 10.1038/s41598-025-01089-w] [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: 08/16/2024] [Accepted: 05/02/2025] [Indexed: 05/14/2025] Open
Abstract
Hepatitis B virus (HBV) infection is a global public health concern with a high burden in the African region. Assessing trends in HBV infection over time can provide insights into the effectiveness of prevention/treatment strategies in different settings. Herein, we investigate trends in active HBV infection and associated risk factors among blood donor candidates from Luanda, Angola. This was a retrospective study conducted with 96,654 medical records of blood donors consulted between 2018 and 2022 at the Angolan National Blood Institute. Participants were screened for hepatitis B surface antigen (HBsAg). Chi-square, Prevalence Ratio, and logistic regression were used to analyse interactions between demographic variables and were deemed significant when p < 0.05. Active HBV infection was 10% (95% CI: 9.4-10.6). Men (AOR: 1.38, p < 0.001), employed (AOR: 3.25, p < 0.001) and non-urbanised regions (AOR: 1.16, p = 0.019), were more likely to contract the HBV, while aged 30 years or older (AOR: 0.78, p < 0.001) and married (AOR: 0.66, p < 0.001), were less likely to contract the infection. From 2018 to 2022, HBV infections increased from 18.2 to 21.9%. Infections increased in under 30 years (31.3-52.5%, p < 0.001), males (91.1 to 91.8%, p = 0.149), urbanised regions (2.7 to 3.3%, p = 0.538), and unmarried (93.9 to 95.8%, p = 0.019). We revealed a highly active HBV infection over the past 5 years in the adult population of Luanda, Angola. Age, gender, occupation, place of residence and marital status have influenced the dissemination of HBV in Angola. Our findings may facilitate the planning and evaluation of the HBV control program in Angola.
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Affiliation(s)
- Cruz S Sebastião
- Centro Nacional de Investigação Científica (CNIC), Luanda, Angola.
- Centro de Investigação em Saúde de Angola (CISA) | Instituto Nacional de Investigação em Saúde (INIS), Luanda, Angola.
- Global Health and Tropical Medicine (GHTM), Associate Laboratory in Translation and Innovation Towards Global Health (LA-REAL), Instituto de Higiene e Medicina Tropical (IHMT), Universidade NOVA de Lisboa (UNL), Rua da Junqueira 100, Lisbon, 1349-008, Portugal.
| | - Michel G Machado
- Instituto Nacional de Sangue (INS), Ministério da Saúde, Luanda, Angola
| | - João Vigário
- Instituto Nacional de Sangue (INS), Ministério da Saúde, Luanda, Angola
| | | | - António Armando
- Centro de Estudos, Investigação Científica e Pós-Graduação, Universidade Privada de Angola, Luanda, Angola
| | - Maria L S Silva
- Faculdade de Medicina (FM), Universidade Katyavala Bwila (UKB), Benguela, Angola
| | - Joana M K Sebastião
- Centro de Investigação em Saúde de Angola (CISA) | Instituto Nacional de Investigação em Saúde (INIS), Luanda, Angola
| | - Eunice Manico
- Instituto Nacional de Sangue (INS), Ministério da Saúde, Luanda, Angola
| | - Deodete Machado
- Instituto Nacional de Sangue (INS), Ministério da Saúde, Luanda, Angola
| | - Victor Pimentel
- Global Health and Tropical Medicine (GHTM), Associate Laboratory in Translation and Innovation Towards Global Health (LA-REAL), Instituto de Higiene e Medicina Tropical (IHMT), Universidade NOVA de Lisboa (UNL), Rua da Junqueira 100, Lisbon, 1349-008, Portugal
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8
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Qin Z, Liu Y, Liu Y, Yang A, Zhang R, Zhang K, Zhang S. Association between resolved hepatitis B virus infection and depression in American adults : a cross-sectional study. Sci Rep 2025; 15:16141. [PMID: 40341244 PMCID: PMC12062217 DOI: 10.1038/s41598-025-99864-2] [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: 09/08/2024] [Accepted: 04/23/2025] [Indexed: 05/10/2025] Open
Abstract
Hepatitis B virus (HBV) infection is a global health concern, and it can potentially affect mental health like depression. Resolved HBV infection, often perceived as a milder form of HBV infection, are often overlooked, and the association between it and depression remains unclear. This study aims to investigate the association between resolved HBV infection and depression. A cross-sectional analysis was conducted using the National Health and Nutrition Examination Survey (NHANES) data from 2005 to 2018, including 20,655 adult Americans. Resolved HBV infection was defined as HBV surface antigen (HBsAg) negative and HBV core antibody (HBcAb) positive. Depression was assessed using the Patient Health Questionnaire-9 (PHQ-9) score. Propensity score matching (PSM) was performed to balance baseline characteristics. Algorithms such as inverse probability of treatment weighting (IPTW) were also applied. Among the participants, 1,551 (7.5%) were reported to have resolved HBV infection. Depression was reported by 1,796 participants (8.7%), with a higher prevalence among those with resolved HBV infection (10.6%) compared to those without HBV infection(8.5%). PSM and IPTW revealed a significantly positive association between resolved HBV infection and depression (PSM: OR = 1.40, 95%CI 1.09-1.79, p = 0.008; IPTW: OR = 1.48, 95%CI 1.26-1.74, p < 0.001). Subgroup and sensitivity analyses supported the robustness of the findings. The results suggest a complex relationship between resolved chronic viral infections and mental health. Based on this finding, it is advisable to conduct psychological monitoring and offer support to individuals who have achieved a functional cure for HBV. Further prospective studies are still needed to reveal the potential mechanism.
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Affiliation(s)
- Zihan Qin
- Hebei Medical University, Shijiazhuang, 050017, China
| | - Yizhuo Liu
- Hebei Medical University, Shijiazhuang, 050017, China
| | - Yifei Liu
- Hebei Medical University, Shijiazhuang, 050017, China
| | - Anqi Yang
- Dongfang Hospital, Beijing University of Chinese Medicine, Beijing, 100078, China
| | - Ruoyi Zhang
- Hebei Medical University, Shijiazhuang, 050017, China.
| | - Kun Zhang
- Hebei Medical University, Shijiazhuang, 050017, China.
| | - Shutian Zhang
- Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, China
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9
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Li J, Zhou J, Li P, Wang Y, Ridderhof N, Al-Tawfiq JA, Brouwer WP, Chen K, de Knegt RJ, Peppelenbosch MP, Hansen BE, Engel MF, Zheng MH, Memish ZA, Eslam M, Janssen HLA, Pan Q, Ayada I. The global prevalence and impact of steatotic liver disease and viral infections: A systematic review and meta-analysis. Hepatol Commun 2025; 9:e0689. [PMID: 40227096 PMCID: PMC11999411 DOI: 10.1097/hc9.0000000000000689] [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: 09/19/2024] [Accepted: 01/22/2025] [Indexed: 04/15/2025] Open
Abstract
BACKGROUND Steatotic liver disease (SLD) affects ~30% of adults worldwide. The global population is continuously threatened by epidemic and endemic viral diseases. This study aims to thoroughly examine the interaction between SLD and major viral diseases. METHODS We systematically searched databases from inception to April 2, 2024, for observational studies recording viral-infected adult patients with eligible data on the presence of hepatic steatosis. RESULTS Six hundred thirty-six eligible studies were included in the analysis of SLD prevalence. Among patients with monoinfections, the highest SLD prevalence was observed in those infected with HCV at 49% (95% CI: 47%-51%), followed by SARS-CoV-2 (39%, 95% CI [34%-44%]), HIV (39%, 95% CI [33%-44%]), and HBV (36%, 95% CI [32%-40%]). Additionally, co-infections, such as HCV-HIV and HBV-HCV, exhibit even higher SLD prevalence. The prevalence of steatohepatitis is particularly high in HIV-infected (24%, 95% CI: 17%-30%) and HCV-infected (18%, 95% CI: 13%-24%) populations. The co-existence of SLD with viral infections was associated not only with the progression of liver disease but also with more severe outcomes of the infections and poorer responses to antiviral treatment. The combination of cardiometabolic risk factors and viral-associated and host factors contributes to the higher risk of SLD in viral-infected populations. CONCLUSIONS SLD is highly prevalent in viral-infected populations, and the reciprocal interactions between SLD and viral diseases exacerbate both conditions, leading to poorer patient outcomes in general.
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Affiliation(s)
- Jiajing Li
- Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - Jiahua Zhou
- Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - Pengfei Li
- Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - Yining Wang
- Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - Nathalie Ridderhof
- Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - Jaffar A. Al-Tawfiq
- Infectious Disease Unit, Specialty Internal Medicine, Johns Hopkins Aramco Healthcare, Dhahran, Saudi Arabia
- Division of Infectious Diseases, Indiana University School of Medicine, Indianapolis, Indiana, USA
- Division of Infectious Diseases, Johns Hopkins University, Baltimore, Maryland, USA
| | - Willem Pieter Brouwer
- Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - Kan Chen
- College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou, China
| | - Robert J. de Knegt
- Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - Maikel P. Peppelenbosch
- Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - Bettina E. Hansen
- Department of Epidemiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - Maarten F.M. Engel
- Medical Library, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - Ming-Hua Zheng
- Department of Hepatology, MAFLD Research Center, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
- Key Laboratory of Diagnosis and Treatment for the Development of Chronic Liver Disease in Zhejiang Province, Wenzhou, China
| | - Ziad A. Memish
- College of Medicine, Al Faisal University, Riyadh, Saudi Arabia
- Hubert Department of Global Health, Rollins School of Public Health, Emory University, Atlanta, USA
| | - Mohammed Eslam
- Storr Liver Centre, Westmead Institute for Medical Research, Westmead Hospital and University of Sydney, NSW, Australia
| | - Harry L. A. Janssen
- Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands
- Toronto Center for Liver Disease, Toronto General Hospital, University of Toronto, Ontario, Canada
| | - Qiuwei Pan
- Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - Ibrahim Ayada
- Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands
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Alkhdir AAM, Mohamedsharif AA, Mohammed IBS, Abbas AM. Seroprevalence and Risk Factors of Hepatitis B Virus Among Newly Diagnosed Cancer Patients in Khartoum State: Implications for Chemotherapy Management and Screening Protocols. JGH Open 2025; 9:e70171. [PMID: 40314027 PMCID: PMC12041132 DOI: 10.1002/jgh3.70171] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2024] [Revised: 04/11/2025] [Accepted: 04/19/2025] [Indexed: 05/03/2025]
Abstract
Aims This study aimed to determine the seroprevalence of hepatitis B virus (HBV) among newly diagnosed cancer patients in Khartoum State, Sudan, prior to chemotherapy initiation and to identify associated risk factors. Methods and Results A cross-sectional study was conducted from October 2022 to April 2023 at various oncology centers in Khartoum State. A total of 300 newly diagnosed cancer patients, aged 18 years and older, were included. Blood samples were screened for Hepatitis B surface antigen (HBsAg) using a rapid immunochromatographic test (ICT) and confirmed by enzyme-linked immunosorbent assay (ELISA). The study found that 31 patients (10.3%) were HBsAg positive. A significant association was observed between HBV positivity and patients' history of blood transfusions (41.9% of positive cases), as well as geographic origin, with higher rates among those from Western Sudan (44.7%) and Central Sudan (40.6%). Patients diagnosed with hematological malignancies exhibited the highest HBV prevalence. Statistical analysis revealed significant correlations between HBV positivity and factors such as age, gender, residence, and transfusion history, indicating these as key risk factors. Conclusion The study reveals a notable HBV seroprevalence among cancer patients in Khartoum, particularly linked to blood transfusion history and specific regions. These findings emphasize the need for routine HBV screening in oncology patients before chemotherapy to prevent reactivation and improve clinical outcomes.
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Abu-Freha N, Shibli S, Etzion O, Afianish Y, Amer J, Abu Kaf H, Zohar N, Yardeni D, Safadi R. Evaluating the influence of maternal anti-HBs status on the antibody levels in vaccinated children. Clin Res Hepatol Gastroenterol 2025; 49:102608. [PMID: 40315984 DOI: 10.1016/j.clinre.2025.102608] [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: 03/22/2025] [Revised: 04/18/2025] [Accepted: 04/28/2025] [Indexed: 05/04/2025]
Abstract
BACKGROUND AND AIMS The mother's Hepatitis B Virus (HBV) vaccination status may impact the child's response. We aimed to investigate the children's vaccine response based on the mother's vaccination status. METHODS In a retrospective study, we included children ≤10 years old born to HBsAg negative mothers, with available maternal and children anti-HBs antibodies. Children of vaccinated and unvaccinated mothers were compared and categorized based on anti-HBs titers: 0-9.9, 10-100, 101-500, 501-1000, and ≥1001 mlU/ml. RESULTS 14,485 children were included. No significant difference in the anti-HBs positivity rate was found among the children of vaccinated and unvaccinated mothers (70.4 % vs. 69.7 %, p = 0.337). Vaccine response in vaccinated vs. unvaccinated mothers was 93.5 % vs. 92.1 % for the first year of age, 87.7 % vs. 87.3 % for age 3 years, and 82.5 % vs. 82.2 % for age 5 years, respectively. Young children (7-36 months) had higher protective titer rates than older children. A higher proportion of the ≥1001 mlU/ml category was recorded among children of mothers with negative or low anti-HBs antibodies in the first year of age, reaching 40.9 %. With age, the proportion of children with 10-100 mlU/ml increased, corresponding to the mother's titer. CONCLUSION The maternal HBV vaccination status does not impact the children's response, but the mother's anti-HBs titers may affect the child's antibody level. Maternal anti-HBs antibody titers may neutralize the vaccine HBsAg to impair the reponse.
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Affiliation(s)
- Naim Abu-Freha
- Institute of Gastroenterology and Hepatology, Clalit, Southern Districit, Beer-Sheva, Israel; Institute of Gastroenterology and Hepatology, Soroka University Medical Center, Beer-Sheva, Israel; Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
| | - Safa Shibli
- Department of Medicine, Liver Institute, Hebrew University, Hadassah Medical Organization, Jerusalem, Israel
| | - Ohad Etzion
- Institute of Gastroenterology and Hepatology, Soroka University Medical Center, Beer-Sheva, Israel; Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel
| | - Yaser Afianish
- Institute of Gastroenterology and Hepatology, Soroka University Medical Center, Beer-Sheva, Israel
| | - Johnny Amer
- Department of Medicine, Liver Institute, Hebrew University, Hadassah Medical Organization, Jerusalem, Israel
| | - Heba Abu Kaf
- Institute of Gastroenterology and Hepatology, Soroka University Medical Center, Beer-Sheva, Israel
| | - Nachum Zohar
- Maternal and Fetal Medicine Service, Obstetrics & Gynecology, Emek Medical Center, Afula, Israel
| | - David Yardeni
- Institute of Gastroenterology and Hepatology, Soroka University Medical Center, Beer-Sheva, Israel; Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel
| | - Rifaat Safadi
- Department of Medicine, Liver Institute, Hebrew University, Hadassah Medical Organization, Jerusalem, Israel
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Wu J, Xie S, Ma Y, He X, Dong X, Shi Q, Wang Q, Li M, Yao N, Yao L. Entecavir for children and adults with chronic hepatitis B. Cochrane Database Syst Rev 2025; 4:CD015536. [PMID: 40260837 PMCID: PMC12012880 DOI: 10.1002/14651858.cd015536.pub2] [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] [Indexed: 04/24/2025]
Abstract
RATIONALE Chronic hepatitis B is a major worldwide public health concern. Entecavir, one nucleos(t)ide analogue antiviral therapy option, is recommended as the first-line drug for chronic hepatitis B in many clinical guidelines. However, none of the guideline recommendations are based on the findings of a systematic review with meta-analysis, where entecavir versus no treatment or placebo are compared directly. OBJECTIVES To evaluate the benefits and harms of entecavir versus no treatment or placebo in children and adults with chronic hepatitis B, who are either hepatitis B e-antigen (HBeAg)-positive or HBeAg-negative. SEARCH METHODS We searched the Cochrane Hepato-Biliary Group Controlled Trials Register, Cochrane Central Register of Controlled Trials, MEDLINE Ovid, Embase Ovid, three other databases, online trial registries, and reference lists, and contacted authors. The latest search was on 19 July 2024. ELIGIBILITY CRITERIA We included randomised clinical trials comparing entecavir versus no treatment or placebo in children or adults, or both, with chronic hepatitis B, and irrespective of treatment history with other antiviral drugs and other viral co-infections. We allowed co-interventions when administered equally to all intervention groups. OUTCOMES The outcomes reported in this abstract and in the summary of findings table are all-cause mortality, health-related quality of life, and proportion of people with serious adverse events at the longest follow-up. RISK OF BIAS We used the Cochrane RoB 2 tool to assess risk of bias in the included trials. SYNTHESIS METHODS We used a random-effects model to meta-analyse outcome results, where possible, and presented the results as a risk ratio (RR) with 95% confidence interval (CI). Where there was considerable heterogeneity, we performed a narrative analysis. We used a fixed-effect model for sensitivity analysis. We used GRADE to evaluate the certainty of evidence. INCLUDED STUDIES We included 22 randomised clinical trials (published from 2005 to 2022) with 2940 participants diagnosed with chronic hepatitis B. All trials had a parallel-group design. The experimental intervention was oral entecavir, with a follow-up duration of 5 weeks to 228 weeks. The comparator in 12 trials was no treatment, and in 10 trials was placebo. Fourteen trials equally administered co-interventions to the trial participants in the entecavir and no treatment and placebo groups. One trial included participants between 14 years and 55 years of age, one trial included only children, 19 trials included only adults, and one trial did not provide the age of participants. SYNTHESIS OF RESULTS Twenty trials contributed data to the quantitative analysis. Ten trials (1379 participants) reported all-cause mortality with a mean follow-up duration of 48.9 weeks (range 5 to 100 weeks). The result was not estimable because no deaths occurred in any of the entecavir and no treatment or placebo groups. None of the trials provided data on health-related quality of life. We are very uncertain about the effect of entecavir versus no treatment or placebo on the proportion of people with serious adverse events (RR 0.66, 95% CI 0.33 to 1.32; absolute risk difference 22 fewer per 1000 (from 44 fewer to 21 more); 15 trials, 1676 participants; very low-certainty evidence). The mean follow-up duration was 58.4 weeks (range 5 weeks to 228 weeks). We downgraded the certainty of evidence for these outcomes to very low, mainly because the overall risk of bias in most trials was with some concerns or high, and serious imprecision (no events or few events). AUTHORS' CONCLUSIONS Given the issues of risk of bias and insufficient power of the included trials and the very low certainty of the available evidence, we could not determine the effect of entecavir versus no treatment or placebo on critical outcomes such as all-cause mortality and serious adverse events. There is a lack of data on health-related quality of life. Given the first-line recommendation and wide usage of entecavir in people with chronic hepatitis B, further evidence on clinically important outcomes, analysed in this review, is needed. FUNDING This Cochrane review had no dedicated funding. REGISTRATION Registration: Entecavir for children and adults with chronic hepatitis B, CD015536 via DOI 10.1002/14651858.CD015536.
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Affiliation(s)
- Jing Wu
- School of Pharmaceutical Science and Technology, Tianjin University, Tianjin, China
| | - Shitong Xie
- School of Pharmaceutical Science and Technology, Tianjin University, Tianjin, China
- Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Canada
| | - Yanfang Ma
- Chinese EQUATOR Centre, Hong Kong Baptist University, Hong Kong, China
| | - Xiaoning He
- School of Pharmaceutical Science and Technology, Tianjin University, Tianjin, China
| | - Xinyue Dong
- School of Pharmaceutical Science and Technology, Tianjin University, Tianjin, China
| | - Qianling Shi
- The First School of Clinical Medicine, Lanzhou University, Lanzhou, China
- Evidence-based Medicine Center, School of Basic Medical Sciences, Lanzhou University, Lanzhou, China
| | - Qi Wang
- Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Canada
| | - Meixuan Li
- Evidence-based Medicine Center, School of Basic Medical Sciences, Lanzhou University, Lanzhou, China
| | - Naijuan Yao
- The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Liang Yao
- Lee Kong Chian School of Medicine, Nanyang Technological University Singapore, Singapore, Singapore
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Orotta M, Munseri P, Massawe RV, Orotta GM, Ebrahim A, Kisali EP, Kajaja S, Shayo B, Meda A. Hepatitis B virus: Prevalence, vaccination coverage and immune responses to immunization among healthcare workers at Muhimbili National Hospital. PLoS One 2025; 20:e0321623. [PMID: 40238849 PMCID: PMC12002445 DOI: 10.1371/journal.pone.0321623] [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: 12/30/2024] [Accepted: 03/10/2025] [Indexed: 04/18/2025] Open
Abstract
BACKGROUND Healthcare workers (HCWs) are at an increased risk of contracting and transmitting the hepatitis B virus (HBV). Vaccination coverage against HBV a cost- effective prevention, remains low among HCWs in some settings. OBJECTIVE To determine the prevalence of HBV infection, vaccination coverage, and immune responses to HBV vaccine among HCWs at Muhimbili National Hospital (MNH) in Dar es Salaam. METHODOLOGY This cross-sectional study used a proportional probability systematic sampling to recruit HCWs from MNH in Dar es Salaam. A structured questionnaire was used to collect social demographic characteristics, infection prevention and control practices, HBV vaccination status and reasons for not vaccinating. Five mLs of a peripheral venous sample was obtained from each participant, the sample was used to test for HBV surface antigen, HBV surface antibody and HBV core antibody for assessing for infection, and vaccine immunity respectively. A Robust Poisson Regression analysis was used to assess factors associated with not vaccinating. RESULTS The prevalence of HBV infection was 5 (1.2%) among the 415 recruited HCWs. Only 192 (46.3%) HCWs were vaccinated and 169 (96%) had protective immunity against HBV infection among 176 participants who had received at least two vaccine doses. HCWs who were laboratory scientist aPR = 2.01, 95% CI (1.35-3.00) and had < 10 years of employment aPR = 1.62, 95% CI (1.04-2.50) were unlikely to vaccinate against HBV. Vaccine unavailability 114 (51.1%), hesitancy 42 (18.8%), time constraints 41 (18.4%) and financial constraints 26 (11.7%) were factors associated with not vaccinating. CONCLUSION Vaccine coverage against HBV among HCWs at MNH is alarmingly low. Vaccine access, subsidizing cost, protecting time for vaccination could improve vaccination uptake. Qualitative studies are needed to assess for reasons for vaccine hesitancy among HCWs.
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Affiliation(s)
- Marythereza Orotta
- Department of Internal Medicine, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania
- Department of Internal Medicine, Muhimbili National Hospital, Dar es Salaam, Tanzania
| | - Patricia Munseri
- Department of Internal Medicine, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania
| | - Regan Valerian Massawe
- Department of Internal Medicine, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania
| | | | - Ashabilan Ebrahim
- Department of Physiology, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania
| | - Eka Patricia Kisali
- Department of Physiology, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania
| | - Stanley Kajaja
- Department of Internal Medicine, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania
| | - Brendan Shayo
- Department of Internal Medicine, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania
| | - Amunga Meda
- Department of Internal Medicine, Muhimbili National Hospital, Dar es Salaam, Tanzania
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Feng W, Li Z, Fan M, Yang S, Shao Y, Liu K, Huang S, Fu S. Health economic evaluation of newborn hepatitis B immunization prevention strategies in Ningbo: a Markov modeling study. Front Public Health 2025; 13:1532604. [PMID: 40308912 PMCID: PMC12040845 DOI: 10.3389/fpubh.2025.1532604] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2024] [Accepted: 03/27/2025] [Indexed: 05/02/2025] Open
Abstract
Background Hepatitis B virus (HBV) infection poses a significant public health challenge in China. The Prevention of mother-to-child Transmission (PMTCT) strategy of combining universal hepatitis B vaccination with hepatitis B immunoglobulin (HBIG) for newborns is crucial in preventing widespread infection. In this study, we conduct health economic evaluation of three strategies: PMTCT, universal vaccination, and non-vaccination for newborns in Ningbo, China. Methods This study developed a decision-Markov model and simulated a cohort of 100,000 newborns to assess the cost-effectiveness and cost-benefit of three strategies from a healthcare system perspective. The primary outputs included total costs, life-years (LYs), quality-adjusted life-years (QALYs), incremental cost-effectiveness ratios (ICERs), benefit-cost ratios (BCRs). One-way and probabilistic sensitivity analyses (PSA) were performed to verify the robustness of the model. Results Among the three strategies, the PMTCT results in the least disease burden and mortality related to hepatitis B. In comparison to a cohort of 100,000 unvaccinated infants, the PMTCT is expected to prevent 6,029 cases of acute symptomatic infections, 27,348 HBV carriers, 4,170 chronic infections, 3,597 cases of cirrhosis, 2,911 cases of hepatocellular carcinoma (HCC), and 3,930 HBV-related deaths. The ICERs for PMTCT and universal vaccination were - 56,371.77 yuan/QALY and - 56,654.77 yuan/QALY, respectively. The BCRs for PMTCT and universal vaccination were 19.13 and 15.95, respectively, when compared to no vaccination. The PSA revealed that all ICER scatter points are situated within the fourth quadrant, and the probability of PMTCT being cost-effective exceeds 90%. Conclusion Implementing universal hepatitis B vaccination with HBIG for newborns in Ningbo demonstrated high cost-effectiveness, making the continuation of the PMTCT strategy highly recommended.
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Affiliation(s)
- Wei Feng
- Fenghua District Center for Disease Control and Prevention, Ningbo, China
| | - Zhengxiong Li
- School of Medical Informatics and Engineering, Xuzhou Medical University, Xuzhou, China
| | - Mingkuan Fan
- School of Medicine, Xiangyang Polytechnic, Xiangyang, China
| | - Sijia Yang
- Ningbo Municipal Center for Disease Control and Prevention, Ningbo, China
| | - Yuqi Shao
- Fenghua District Center for Disease Control and Prevention, Ningbo, China
| | - Kui Liu
- Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou, China
| | | | - Sanjun Fu
- Fenghua District Center for Disease Control and Prevention, Ningbo, China
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15
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Kremer-Flach K, Zimmermann R, an der Heiden M, Dudareva S. Estimated number of people infected with hepatitis B and C virus in Germany in 2013: a baseline prevalence estimate using the workbook method. Front Public Health 2025; 13:1471256. [PMID: 40260160 PMCID: PMC12009770 DOI: 10.3389/fpubh.2025.1471256] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2024] [Accepted: 02/24/2025] [Indexed: 04/23/2025] Open
Abstract
Introduction Hepatitis B (HBV) and hepatitis C (HCV) viral infections are uncommon in Germany, though these infections have a higher prevalence among certain subpopulations, such as some first-generation migrant groups, people who inject drugs (PWID), and HIV-positive men who have sex with men (HIV+MSM). Repeated estimates of the number of people infected with HBV and HCV are essential to facilitate the monitoring and elimination efforts by 2030. We estimated the total number of people infected with HBV and HCV in Germany, and the number in each specific subpopulation. We based our calculations on data from 2013, a year that we strategically chose to coincide with the availability of data from serological surveys, the advent of highly effective antiviral therapy for HCV, and significant migrant flows in the following years. Methods We used the workbook method, a technique that combines subpopulation size and prevalence data. We included different population groups (general population excluding vulnerable groups, migrants stratified by nationality, people who inject opioids (PWIO) and HIV+MSM). We estimated the number of people infected with HBV and the number of people infected with HCV. Estimates of the number of people infected with HBV and HCV are reported with the lower and upper confidence limits. Results We estimated 228,000 (179,000-291,000) HBV-infected adults (≥ 18 years of age) in Germany in 2013, of whom 41% (n = 93,000 [52,000-169,000]) were in the general population excluding vulnerable groups. Another 58% (132,000; 126,000-137,000) were migrants, 1.0% (2,400; 900-6,200) PWIO and 0.4% (1,000; 800-1,400) were HIV+MSM. We estimated 214,000 (135,000-340,000) HCV-infected adults in Germany in 2013, of whom 47% (100,000; 38,000-267,000) were in the general population excluding vulnerable groups, 26.0% (56,000; 47,000-66,000) were migrants, 26% (56,000; 50,000-62,000) were PWIO, and 1.0% (2,500; 2,200-2,800) were HIV+MSM, respectively. Discussion Our results indicate that more than half of HBV-infected individuals were migrants, and more than half of HCV-infected individuals were PWIO or migrants. This highlights the importance of including relevant subpopulations in national estimates, surveillance, prevention, and therapy. Our estimates serve as a baseline reference for subsequent updates and ongoing monitoring of HBV and HCV epidemiology in Germany.
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Affiliation(s)
- Katrin Kremer-Flach
- Department of Infectious Disease Epidemiology, Robert Koch Institute, Berlin, Germany
- European Program for Intervention Epidemiology Training (EPIET), European Centre for Disease Prevention and Control (ECDC), Stockholm, Sweden
- Postgraduate Training for Applied Epidemiology (PAE), Robert Koch Institute, Berlin, Germany
| | - Ruth Zimmermann
- Department of Infectious Disease Epidemiology, Robert Koch Institute, Berlin, Germany
| | | | - Sandra Dudareva
- Department of Infectious Disease Epidemiology, Robert Koch Institute, Berlin, Germany
- Institute of Public Health, Riga Stradins University, Riga, Latvia
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Liang H, Zheng X, Mao Q, Yang J, Ruan Q, Wu C, Liu Y, Chen S, Zhang L, Zhang M, Zhuang H, Lin L, Chen S. Comparative efficacy and safety of pegylated interferon-alpha monotherapy vs combination therapies with entecavir or tenofovir in chronic hepatitis B patients. Microbiol Spectr 2025; 13:e0269424. [PMID: 40172187 PMCID: PMC12054097 DOI: 10.1128/spectrum.02694-24] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2024] [Accepted: 02/03/2025] [Indexed: 04/04/2025] Open
Abstract
Current treatments for chronic hepatitis B (CHB) virus involve nucleos(t)ide analogs and pegylated interferon-alpha (PEG-IFNα). This study compares the efficacy and safety of PEG-IFNα monotherapy with its combinations with entecavir (ETV) and tenofovir disoproxil fumarate (TDF) in managing CHB. We included 147 treatment-naïve patients divided into three groups: Group A (PEG-IFNα-2b with ETV), Group B (PEG-IFNα-2b with TDF), and Group C (PEG-IFNα-2b monotherapy). Evaluations occurred every 12 weeks up to 48 weeks. The Kaplan-Meier method showed no significant differences in cumulative HBsAg loss, but HBV DNA clearance rates were higher in the TDF group than in the ETV group (P = 0.01). Higher incidences of elevated alanine aminotransferase (ALT), aspartate aminotransferase, and thrombocytopenia were observed in the TDF group compared to other groups. After propensity score matching, the TDF group had a higher undetectable HBV DNA rate than the IFN group, but no significant differences in HBsAg clearance rates. Both TDF and ETV groups achieved more significant HBsAg reductions from baseline to week 48 than the IFN group (P < 0.05). ETV showed a lower HBeAg clearance rate (30.00% vs 87.50%, P < 0.05) but higher ALT normalization (76.92% vs 45.45%, P < 0.05). In the TDF group, patients with lower baseline HBsAg levels, high ALT levels, and lower aspartate aminotransferase-to-platelet ratio index (APRI) scores were more likely to achieve HBsAg loss. These findings suggest that TDF and ETV are effective for viral suppression, with TDF showing superior HBV DNA clearance but more adverse events. IMPORTANCE This study investigates how different treatments for chronic hepatitis B (CHB), a widespread liver infection, compare in effectiveness and safety. By evaluating the use of pegylated interferon-alpha alone and in combination with two other drugs, entecavir and tenofovir disoproxil fumarate (TDF), researchers found that TDF offers better viral suppression but also comes with more side effects. For patients receiving TDF combined with PEG-IFN therapy, low HBsAg levels, elevated alanine aminotransferase levels, and lower APRI scores were associated with a higher likelihood of achieving HBsAg loss. Consistent with previous findings, this study confirms the benefits of nucleos(t)ide analog plus PEG-IFN therapy for CHB treatment and further explores which patients are more likely to benefit from combination therapy. Furthermore, this study underscores the importance of further monitoring adverse events in patients receiving combination therapy.
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Affiliation(s)
- Huiqing Liang
- Hepatology Unit, Xiamen Hospital of Traditional Chinese Medicine, Xiamen, Fujian, China
| | - Xiaoting Zheng
- Hepatology Unit, Xiamen Hospital of Traditional Chinese Medicine, Xiamen, Fujian, China
| | - Qianguo Mao
- Hepatology Unit, Xiamen Hospital of Traditional Chinese Medicine, Xiamen, Fujian, China
| | - Jiaen Yang
- Hepatology Unit, Xiamen Hospital of Traditional Chinese Medicine, Xiamen, Fujian, China
| | - Qingfa Ruan
- Hepatology Unit, Xiamen Hospital of Traditional Chinese Medicine, Xiamen, Fujian, China
| | - Chuncheng Wu
- Hepatology Unit, Xiamen Hospital of Traditional Chinese Medicine, Xiamen, Fujian, China
| | - Yaoyu Liu
- Hepatology Unit, Xiamen Hospital of Traditional Chinese Medicine, Xiamen, Fujian, China
| | - Siyan Chen
- School of Clinical Medicine, Fujian University of Traditional Chinese Medicine, Fujian, China
| | - Luyun Zhang
- School of Clinical Medicine, Fujian University of Traditional Chinese Medicine, Fujian, China
| | - Manying Zhang
- Hepatology Unit, Xiamen Hospital of Traditional Chinese Medicine, Xiamen, Fujian, China
| | - Hongli Zhuang
- Department of Traditional Chinese Medicine, First Affiliated Hospital of Xiamen University, Xiamen, Fujian Province, China
| | - Li Lin
- Hepatology Unit, Xiamen Hospital of Traditional Chinese Medicine, Xiamen, Fujian, China
| | - Shaodong Chen
- School of Medicine, Xiamen University, Xiamen, Fujian Province, China
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Erdoğdu Hİ, Bozlak ÇEB, Başak M, Başar SK, Topaloğlu İ, Tural K. Anti-HBs Levels 18-26 Years After the Initial Hepatitis B Vaccination Series in a Low-to-Medium Prevalence Region: Is a Booster Dose or a Second Vaccine Series Necessary? Curr Microbiol 2025; 82:223. [PMID: 40169411 DOI: 10.1007/s00284-025-04211-3] [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: 11/29/2024] [Accepted: 03/22/2025] [Indexed: 04/03/2025]
Abstract
This cross-sectional study aimed to evaluate the persistence of immunity provided by hepatitis B (Hep B) vaccine 18-26 years after primary vaccination among 628 participants. Blood samples were collected for Hep B surface antigen (HBsAg), anti-HBs antibody (anti-HBs), and core antibody (anti-HBc) analyses. For participants with anti-HBs levels of < 10 mIU/mL, booster dose was administered and anti-HBs titers were monitored 4-6 weeks after vaccination was completed. If the response to Hep B vaccine was inadequate, two additional Hep B vaccine doses were administered. Of the 628 participants, 269 were excluded based on the exclusion criteria, and 359 were included in the final analysis. Three participants were found to be HBsAg-positive, resulting in an HBsAg carrier rate of 0.83%. Moreover, 55.4% participants had anti-HBs levels of ≥ 10 mIU/mL, with a geometric mean concentration (GMC) of 82.59 mIU/mL (95% confidence interval [CI]). Among 125 participants with anti-HBs levels of < 10 mIU/mL, 93.1% reached anti-HBs levels of ≥ 10 mIU/mL after booster dose, with a GMC of 493.47 mIU/mL. A prebooster anti-HBs cutoff level of 1.28 mIU/mL was predictive for an immune response, with a sensitivity and specificity of 71.2% and 71.4%, respectively (p = 0.001, 95% CI, likelihood ratio: 2.49). Among 14 participants unresponsive to the booster dose, 78.5% responded to the second vaccine series with a GMC of 670.82 mIU/mL. Approximately 44.6% of participants required a booster dose 18-26 years after primary vaccination. Prebooster anti-HBs titration may predict the response to booster doses. Further studies with larger groups are needed to confirm these findings.
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Affiliation(s)
- Halil İbrahim Erdoğdu
- Department of Internal Medicine, Health Research Center, Kafkas University, Kars, Turkey.
| | | | | | | | - İhsan Topaloğlu
- Department of Chest Diseases, Health Research Center, Kafkas University, Kars, Turkey
| | - Kevser Tural
- Department of Thoracic Cardiovascular Surgery, Health ScıEnces University Mehmet Akif Ersoy Hospital, Istanbul, Turkey
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Sam NB, Majeed SF, Dramani A. Unraveling Demographic Patterns in Hepatitis B Clinical and Laboratory Profiles: Insights From a Ghanaian Cohort: A Retrospective Study. Health Sci Rep 2025; 8:e70689. [PMID: 40260046 PMCID: PMC12010205 DOI: 10.1002/hsr2.70689] [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: 07/05/2024] [Revised: 03/20/2025] [Accepted: 04/03/2025] [Indexed: 04/23/2025] Open
Abstract
Background and Aims The influence of age and gender on the manifestations of Hepatitis B (HB) disease is underexplored and yields varied findings. This study assessed the impact of age and gender on HB disease manifestations in a Ghanaian population. Methods This retrospective study evaluated 569 patients at Tamale Teaching Hospital. Disease manifestations were compared separately between male and female patients across different age groups and among four distinct age groups within male and female patients. Results It revealed a male-to-female ratio of 5.1:1, with significant differences observed among age categories. HBsAg was significantly more prevalent in adult males (p < 0.05), while polydipsia showed equal prevalence between genders (p < 0.05). Female adults exhibited higher rates of constipation and palpitation compared to males (p < 0.05). In older patients, females had higher ALT and HBeAg prevalence than males (p < 0.05). Disease manifestation did not significantly differ by gender among children and younger patients (p > 0.05). Among males, viral load differed significantly across age groups and correlated positively with age (p < 0.05). Females showed positive correlations of jaundice, HBeAg, low globulin, and high AST with age (p < 0.05), but nausea was negatively correlated (p < 0.05). Conclusion This study highlights unique clinical and laboratory features in reproductive-aged female HB patients.
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Affiliation(s)
- Napoleon Bellua Sam
- Department of Medical Research and InnovationSchool of Medicine, University for Development StudiesTamaleGhana
| | - Saeed Folorunsho Majeed
- Department of Biological ScienceFaculty of Biosciences, University for Development StudiesTamaleGhana
| | - Adams Dramani
- Department of Medical Research and InnovationSchool of Medicine, University for Development StudiesTamaleGhana
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Pei W, Li J, Lei S, Nie S, Liu L. Burden of major cancers in China attributable to modifiable risk factors: Predictions from 2012 to 2035. Int J Cancer 2025; 156:1369-1379. [PMID: 39503513 DOI: 10.1002/ijc.35233] [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: 05/31/2024] [Revised: 09/23/2024] [Accepted: 10/02/2024] [Indexed: 11/08/2024]
Abstract
The cancer burden continues to escalate in China. This study was designed to quantify the burden of deaths attributable to modifiable risk factors for major cancers in China from 2012 to 2035, and to provide evidence-based recommendations for cancer management. Using nationally representative data on risk factors and cancer mortality, a comparative risk assessment approach was employed to calculate the temporal trend of population-attributable fractions (PAFs) for 15 modifiable risk factors associated with major cancers in China. The PAF for modifiable risk factors decreased from 64.5% (95% uncertainty interval [UI]: 46.2%-75.3%) in 2012 to 59.3% (95% UI: 40.6%-71.2%) in 2035. Attributable deaths increased from 1,309,990 (95% UI: 938,217-1,529,170) in 2012 to 1,313,418 (95% UI: 898,411-1,577,189) in 2035, while attributable disability-adjusted life years (DALYs) rose from 28,488,120 (95% UI: 20,471,859-33,308,237) to 33,017,705 (95% UI: 22,730,814-39,564,735). Between 2012 and 2035, the top three risk factors contributing to cancer burden shifted from smoking, insufficient fruit intake and particulate matter <2.5 μm in diameter (PM2.5) exposure to smoking, physical inactivity, and inadequate fruit intake. Controlling modifiable risk factors at recommended levels by 2020 could have prevented around 890,000 deaths and 2.2 million DALYs by 2035. The proportion of cancer burden due to modifiable risk factors is projected to decrease, but the absolute number continues to rise. Adhering to an optimal lifestyle could prevent ~40% of cancer deaths by 2035. Key modifiable risk factors including smoking, physical inactivity, and insufficient intake of fruits require high attention.
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Affiliation(s)
- Wei Pei
- Department of Epidemiology and Biostatistics, Ministry of Education Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China
| | - Jia Li
- Department of Epidemiology and Biostatistics, Ministry of Education Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China
| | - Shengxi Lei
- Wuhan Britain-China School, Wuhan, People's Republic of China
| | - Shaofa Nie
- Department of Epidemiology and Biostatistics, Ministry of Education Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China
| | - Li Liu
- Department of Epidemiology and Biostatistics, Ministry of Education Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China
- Hubei Provincial Clinical Research Center for Colorectal Cancer, Wuhan, People's Republic of China
- Wuhan Clinical Research Center for Colorectal Cancer, Wuhan, People's Republic of China
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20
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Berhanu L, Desye B, Daba C, Berihun G, Geto AK. Seroprevalence and risk factors of hepatitis B virus infection among healthcare workers in Africa: A systematic review and meta-analysis. PLoS One 2025; 20:e0319986. [PMID: 40131963 PMCID: PMC11936272 DOI: 10.1371/journal.pone.0319986] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2024] [Accepted: 02/11/2025] [Indexed: 03/27/2025] Open
Abstract
BACKGROUND Healthcare workers are at an increased risk of hepatitis B virus infection due to potential exposure to blood and other infectious materials. The infection can lead to acute liver disease and chronic liver complications such as cirrhosis and liver cancer. It can impact workforce health, leading to absenteeism, and increased healthcare costs. Hence, this study aimed to determine the seroprevalence and risk factors of the hepatitis B virus among healthcare workers in Africa. MATERIALS AND METHODS The protocol for this systematic review and meta-analysis was registered on PROSPERO with the registration number CRD42024556654. Literatures were searched from PubMed, Science Direct, HINARI, African Online Journal, Google Scholar, Google, Semantic Scholar, and Directory of Open Access Journals using relevant search terms. The process of searching relevant articles was completed on 1 August 2024. Studies with a quality evaluation indicator score of 50% or above were included in this study. The random effect model was used to measure the pooled seroprevalence and associated factors of hepatitis B virus infection among healthcare workers in Africa. The finding of the meta-analysis was presented using forest plots with a 95% confidence interval. RESULT Among 26 studies selected for meta-analysis, 6983 participants were included. The inclusion of 26 studies showed that the pooled prevalence of hepatitis B virus infection among healthcare workers was 17.2% (95% CI: 8.36, 26.04). Healthcare workers diagnosed with liver disease were 5.01 times more likely to having hepatitis B virus infection compared to those who were not diagnosed (POR = 5.01: 95% CI; 2.25,7.77). In addition, healthcare workers who did not receive technical training were 2.70 times more likely to having HBV infection than those who received training (POR = 2.70:95% CI; 1.10, 4.30). Furthermore, healthcare workers aged 40 years and above were 2.53 times more likely to having hepatitis B virus infection than young healthcare workers (POR = 2.53: 95% CI; 1.29,3.77). CONCLUSION The pooled prevalence of hepatitis B virus infection was high. Previously diagnosed liver diseases, the absence of technical training, and the age of healthcare workers were the factors influencing the pooled prevalence of HBV infection among healthcare workers. Hence, providing appropriate medical follow-up for healthcare workers diagnosed with liver disease, comprehensive training and education, and early detection and diagnosis of healthcare workers aged 40 years and above are the most important interventions to prevent the risk of hepatitis B virus infection.
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Affiliation(s)
- Leykun Berhanu
- Department of Environmental Health, College of Medicine and Health Sciences, Wollo University, Dessie, Ethiopia
| | - Belay Desye
- Department of Environmental Health, College of Medicine and Health Sciences, Wollo University, Dessie, Ethiopia
| | - Chala Daba
- Department of Environmental Health, College of Medicine and Health Sciences, Wollo University, Dessie, Ethiopia
- National Centre for Epidemiology and Population Health, The Australian National University, Canberra, ACT, Australia
| | - Gete Berihun
- Department of Environmental Health, College of Medicine and Health Sciences, Debre Markos University, Debre Markos, Ethiopia
| | - Abebe Kassa Geto
- Department of Public Health, College of Health Sciences, Woldia University, Woldia, Ethiopia
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21
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Paschereit A, Greese V, Sakurayama K, Duerr M, Halleck F, Liefeldt L, Choi M, Budde K, Naik MG. Impact of Hepatitis B Infection on Patient and Graft Survival After Kidney Transplantation. J Clin Med 2025; 14:2124. [PMID: 40142932 PMCID: PMC11943450 DOI: 10.3390/jcm14062124] [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: 02/20/2025] [Revised: 03/11/2025] [Accepted: 03/13/2025] [Indexed: 03/28/2025] Open
Abstract
Objectives: Chronic Hepatitis B virus (HBV) infection is a significant global health issue, with dialysis patients at increased risk and reduced response to HBV vaccination. The effects of HBV serological status on kidney transplant outcomes, particularly for patients with resolved or inactive HBV infection, needs more data, especially from current era. This study evaluated the impact of chronic and non-active HBV infection on patient and graft survival after kidney transplantation. Methods: Retrospective analysis was conducted of kidney-only transplant recipients at our center from 1 January 1990 to 31 August 2019 (end of observation). Patients were grouped by their HBV serostatus before transplantation into three categories: HBV negative (HBsAg-/Anti-Hbc-), non-active HBV infection (HbsAg-/Anti-Hbc+) and chronic HBV infection (HbsAg+/Anti-Hbc+). Primary outcomes included patient survival, graft survival, and overall graft and patient survival, analyzed using Kaplan-Meier (KM) curves, log-rank tests, Restricted mean survival times (RMST), and Accelerated failure time (AFT) models. Results: Among 2490 patients, 2197 were HBV negative, 218 had non-active HBV, and 75 had chronic HBV. Over a mean follow-up of 8.1 years, mortality and graft failure rates were highest in chronic HBV patients (49% and 37%), followed by non-active HBV (39% and 29%) and HBV-negative patients (30% and 20%). KM analysis revealed significantly lower overall survival rates for chronic HBV and non-active HBV groups compared to HBV-negative patients (p = 0.006). RMST confirmed significant reductions in survival for the non-active group (12.57 vs. 14.17 years, p = 0.007). Cox regression and AFT models identified older recipient/donor age, Hepatitis-C-virus coinfection, and broad antigen mismatches as negative predictors, while living donors improved outcomes. Conclusions: While unadjusted Kaplan-Meier curves and RMST analysis suggested differences in patient and graft survival, further thorough multivariable AFT analysis did not show a significant association between non-active or chronic HBV infection and patient or graft survival after kidney transplantation.
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Affiliation(s)
- Anissa Paschereit
- Department of Nephrology and Medical Intensive Care, Charité-Berlin University Medicine, Charitéplatz 1, 10117 Berlin, Germany; (V.G.); (K.S.); (M.D.); (F.H.); (L.L.); (M.C.); (K.B.); (M.G.N.)
| | - Vivien Greese
- Department of Nephrology and Medical Intensive Care, Charité-Berlin University Medicine, Charitéplatz 1, 10117 Berlin, Germany; (V.G.); (K.S.); (M.D.); (F.H.); (L.L.); (M.C.); (K.B.); (M.G.N.)
| | - Kayo Sakurayama
- Department of Nephrology and Medical Intensive Care, Charité-Berlin University Medicine, Charitéplatz 1, 10117 Berlin, Germany; (V.G.); (K.S.); (M.D.); (F.H.); (L.L.); (M.C.); (K.B.); (M.G.N.)
| | - Michael Duerr
- Department of Nephrology and Medical Intensive Care, Charité-Berlin University Medicine, Charitéplatz 1, 10117 Berlin, Germany; (V.G.); (K.S.); (M.D.); (F.H.); (L.L.); (M.C.); (K.B.); (M.G.N.)
- Boehringer Ingelheim, Friedrichstraße 70, 10117 Berlin, Germany
| | - Fabian Halleck
- Department of Nephrology and Medical Intensive Care, Charité-Berlin University Medicine, Charitéplatz 1, 10117 Berlin, Germany; (V.G.); (K.S.); (M.D.); (F.H.); (L.L.); (M.C.); (K.B.); (M.G.N.)
| | - Lutz Liefeldt
- Department of Nephrology and Medical Intensive Care, Charité-Berlin University Medicine, Charitéplatz 1, 10117 Berlin, Germany; (V.G.); (K.S.); (M.D.); (F.H.); (L.L.); (M.C.); (K.B.); (M.G.N.)
| | - Mira Choi
- Department of Nephrology and Medical Intensive Care, Charité-Berlin University Medicine, Charitéplatz 1, 10117 Berlin, Germany; (V.G.); (K.S.); (M.D.); (F.H.); (L.L.); (M.C.); (K.B.); (M.G.N.)
| | - Klemens Budde
- Department of Nephrology and Medical Intensive Care, Charité-Berlin University Medicine, Charitéplatz 1, 10117 Berlin, Germany; (V.G.); (K.S.); (M.D.); (F.H.); (L.L.); (M.C.); (K.B.); (M.G.N.)
| | - Marcel G. Naik
- Department of Nephrology and Medical Intensive Care, Charité-Berlin University Medicine, Charitéplatz 1, 10117 Berlin, Germany; (V.G.); (K.S.); (M.D.); (F.H.); (L.L.); (M.C.); (K.B.); (M.G.N.)
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Kim DH, Choi YM, Jang J, Kim Z, Kim BJ. Distinct phylogeographic distributions and frequencies of precore and basal core promoter mutations between HBV subgenotype C1 rt269L and rt269I types. Sci Rep 2025; 15:9315. [PMID: 40102552 PMCID: PMC11920224 DOI: 10.1038/s41598-025-94286-6] [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: 02/07/2025] [Accepted: 03/12/2025] [Indexed: 03/20/2025] Open
Abstract
Hepatitis B virus (HBV) genotype C exhibits two distinct polymorphisms in its viral polymerase: rt269I and rt269L. Recently, we reported that there are distinct virological and clinical profiles between chronic patients with subgenotype C2 with the rt269I polymorphism and those with the rt269L polymorphism, with the latter being more closely related to liver disease severity. This study explored the phylogenetic and geographic distributions, as well as the mutation frequencies, of precore (T1858C/G1896A) and basal core promoter (BCP) (A1762T/G1764A) mutations between these two types within the HBV subgenotype C1. Analysis of 408 HBV/C1 full-genome sequences from GenBank revealed clear phylogenetic separation between rt269L and rt269I in subgenotype C1. Geographically, rt269I strains within subgenotype C1 are predominant in Southwest Asia (e.g., Thailand and Bangladesh), whereas rt269L strains are more common in East Asia and Southeast Asia (e.g., Vietnam, China, and Hong Kong). Notably, compared with rt269L in subgenotype C2, rt269I presented higher frequencies of the C1858 and BCP mutations but lower frequencies of the G1896A mutation. These findings suggest significantly distinct phylogeographic and mutational characteristics of the rt269L and rt269I types of subgenotype C1, impacting clinical outcomes and evolutionary trajectories.
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Affiliation(s)
- Dong Hyun Kim
- Department of Microbiology and Immunology, College of Medicine, Seoul National University, Seoul, Republic of Korea
- Department of Biomedical Sciences, College of Medicine, Seoul National University, Seoul, Republic of Korea
| | - Yu-Min Choi
- Department of Microbiology and Immunology, College of Medicine, Seoul National University, Seoul, Republic of Korea
- Department of Biomedical Sciences, College of Medicine, Seoul National University, Seoul, Republic of Korea
| | - Junghwa Jang
- Department of Microbiology and Immunology, College of Medicine, Seoul National University, Seoul, Republic of Korea
- Department of Biomedical Sciences, College of Medicine, Seoul National University, Seoul, Republic of Korea
- BK21 FOUR Biomedical Science Project, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Ziyun Kim
- Department of Microbiology and Immunology, College of Medicine, Seoul National University, Seoul, Republic of Korea
- Department of Biomedical Sciences, College of Medicine, Seoul National University, Seoul, Republic of Korea
- BK21 FOUR Biomedical Science Project, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Bum-Joon Kim
- Department of Microbiology and Immunology, College of Medicine, Seoul National University, Seoul, Republic of Korea.
- Department of Biomedical Sciences, College of Medicine, Seoul National University, Seoul, Republic of Korea.
- BK21 FOUR Biomedical Science Project, Seoul National University College of Medicine, Seoul, Republic of Korea.
- Institute of Endemic Disease, Seoul National University Medical Research Center (SNUMRC), Seoul, Republic of Korea.
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23
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Liu F, Wang Z, Song Y, Tian T, Li R, Qiao J, Huang S, Wang Y. The impact of HBV, HCV, or syphilis infections on embryo and pregnancy outcomes in couples undergoing IVF treatment: a matched cohort study. Hum Reprod Open 2025; 2025:hoaf015. [PMID: 40171332 PMCID: PMC11961197 DOI: 10.1093/hropen/hoaf015] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2024] [Revised: 02/17/2025] [Indexed: 04/03/2025] Open
Abstract
STUDY QUESTION Do infectious diseases (hepatitis B virus [HBV], hepatitis C virus [HCV], and syphilis) impact embryo quality, pregnancy, and neonatal outcomes following a complete IVF cycle? SUMMARY ANSWER Infections with HBV, HCV, or syphilis do not have detrimental impacts on live birth rates or neonatal outcomes in couples following a complete IVF cycle. WHAT IS KNOWN ALREADY Maternal or paternal infections with HBV, HCV, or syphilis may decrease the clinical pregnancy rate, result in poorer embryo outcomes, and lower offspring birth weight. However, there is significant controversy regarding these effects across existing studies, highlighting the need for further research. STUDY DESIGN SIZE DURATION This is a retrospective matched cohort study. Data were obtained from the clinical database of couples who underwent IVF treatment at a single academically affiliated fertility clinic from January 2011 to December 2019, with follow-up extending to December 2020. Out of 180 666 complete cycles recorded, 2443 cycles fulfilled our inclusion criteria. PARTICIPANTS/MATERIALS SETTING METHODS In cycles that fulfilled our inclusion criteria, there were 1997 cycles in the HBV study group, 154 cycles in the HCV study group, and 292 cycles in the syphilis study group. Each study cycle was paired with four controls based on participant age and the timing of IVF treatment, resulting in 7988 controls for the HBV group, 616 controls for the HCV group, and 1169 controls for the syphilis group. Infections could be either single-parent or biparental. The primary outcome was live birth per complete cycle (i.e. fresh cycle plus subsequent frozen-thawed cycles). Subgroup analyses were conducted dividing cycles into maternal infection and paternal infection. MAIN RESULTS AND THE ROLE OF CHANCE In the HBV group, pregnancy outcomes (clinical pregnancy, miscarriage, and live birth rates) and neonatal birth weight were similar to that of the controls. In the HCV group, no significant differences from the controls were observed except for a lower clinical pregnancy rate in the study group (36.4% vs 42.2%, adjusted β and 95% CI: 0.62 [0.39-0.96]). Similarly, no significant differences were found in pregnancy or neonatal outcomes between the syphilis group and the control group. As for subgroup analyses, the male-only HBV infection subgroup showed a higher miscarriage rate in the study group than in the control group (22.5% vs 17.7%, adjusted β and 95% CI: 1.56 [1.07-2.28]). For the HCV and syphilis subgroups, none of the outcomes showed significant differences between either the female-only infection or male-only infection subgroups and the controls. LIMITATIONS REASONS FOR CAUTION Although potential confounders were considered and adjusted for, residual bias may still exist due to the study design. The inclusion of participants solely from a single center limited the generalizability of our findings to a broader context. WIDER IMPLICATIONS OF THE FINDINGS We presented a comprehensive overview of the impact of prevalent infectious diseases on IVF outcomes, hoping to address uncertainties surrounding the decisions of couples infected with these diseases and to assist in preventing adverse reproductive outcomes in clinical practice. STUDY FUNDING/COMPETING INTERESTS This study was supported by the National Natural Science Foundation of China (82204052), the National Key R&D Program of China (2022YFC2705305), and the Clinical key project of Peking University Third Hospital (BYSYZD2023007). The authors declare no competing interests. TRIAL REGISTRATION NUMBER N/A.
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Affiliation(s)
- Fang Liu
- Department of Obstetrics and Gynecology, Center for Reproductive Medicine, Peking University Third Hospital, Beijing, The People’s Republic of China
- National Clinical Research Center for Obstetrics and Gynecology, Peking University Third Hospital, Beijing, The People’s Republic of China
- State Key Laboratory of Female Fertility Promotion, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, The People’s Republic of China
- Key Laboratory of Assisted Reproduction, Peking University, Ministry of Education, Beijing, The People’s Republic of China
- Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology, Peking University Third Hospital, Beijing, The People’s Republic of China
| | - Zheng Wang
- Department of Obstetrics and Gynecology, Center for Reproductive Medicine, Peking University Third Hospital, Beijing, The People’s Republic of China
- National Clinical Research Center for Obstetrics and Gynecology, Peking University Third Hospital, Beijing, The People’s Republic of China
- State Key Laboratory of Female Fertility Promotion, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, The People’s Republic of China
- Key Laboratory of Assisted Reproduction, Peking University, Ministry of Education, Beijing, The People’s Republic of China
- Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology, Peking University Third Hospital, Beijing, The People’s Republic of China
| | - Ying Song
- Department of Obstetrics and Gynecology, Center for Reproductive Medicine, Peking University Third Hospital, Beijing, The People’s Republic of China
- National Clinical Research Center for Obstetrics and Gynecology, Peking University Third Hospital, Beijing, The People’s Republic of China
- State Key Laboratory of Female Fertility Promotion, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, The People’s Republic of China
- Key Laboratory of Assisted Reproduction, Peking University, Ministry of Education, Beijing, The People’s Republic of China
- Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology, Peking University Third Hospital, Beijing, The People’s Republic of China
| | - Tian Tian
- Department of Obstetrics and Gynecology, Center for Reproductive Medicine, Peking University Third Hospital, Beijing, The People’s Republic of China
- National Clinical Research Center for Obstetrics and Gynecology, Peking University Third Hospital, Beijing, The People’s Republic of China
- State Key Laboratory of Female Fertility Promotion, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, The People’s Republic of China
- Key Laboratory of Assisted Reproduction, Peking University, Ministry of Education, Beijing, The People’s Republic of China
- Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology, Peking University Third Hospital, Beijing, The People’s Republic of China
| | - Rong Li
- Department of Obstetrics and Gynecology, Center for Reproductive Medicine, Peking University Third Hospital, Beijing, The People’s Republic of China
- National Clinical Research Center for Obstetrics and Gynecology, Peking University Third Hospital, Beijing, The People’s Republic of China
- State Key Laboratory of Female Fertility Promotion, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, The People’s Republic of China
- Key Laboratory of Assisted Reproduction, Peking University, Ministry of Education, Beijing, The People’s Republic of China
- Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology, Peking University Third Hospital, Beijing, The People’s Republic of China
| | - Jie Qiao
- Department of Obstetrics and Gynecology, Center for Reproductive Medicine, Peking University Third Hospital, Beijing, The People’s Republic of China
- National Clinical Research Center for Obstetrics and Gynecology, Peking University Third Hospital, Beijing, The People’s Republic of China
- State Key Laboratory of Female Fertility Promotion, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, The People’s Republic of China
- Key Laboratory of Assisted Reproduction, Peking University, Ministry of Education, Beijing, The People’s Republic of China
- Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology, Peking University Third Hospital, Beijing, The People’s Republic of China
| | - Shuo Huang
- Department of Obstetrics and Gynecology, Center for Reproductive Medicine, Peking University Third Hospital, Beijing, The People’s Republic of China
- National Clinical Research Center for Obstetrics and Gynecology, Peking University Third Hospital, Beijing, The People’s Republic of China
- State Key Laboratory of Female Fertility Promotion, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, The People’s Republic of China
- Key Laboratory of Assisted Reproduction, Peking University, Ministry of Education, Beijing, The People’s Republic of China
- Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology, Peking University Third Hospital, Beijing, The People’s Republic of China
| | - Yuanyuan Wang
- Department of Obstetrics and Gynecology, Center for Reproductive Medicine, Peking University Third Hospital, Beijing, The People’s Republic of China
- National Clinical Research Center for Obstetrics and Gynecology, Peking University Third Hospital, Beijing, The People’s Republic of China
- State Key Laboratory of Female Fertility Promotion, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, The People’s Republic of China
- Key Laboratory of Assisted Reproduction, Peking University, Ministry of Education, Beijing, The People’s Republic of China
- Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology, Peking University Third Hospital, Beijing, The People’s Republic of China
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24
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Xue M, Wu C, Liu K, Lu Q, Ding Z, Wang X, Fu T, Lin J, Wu H. Time series analysis and scaling law characteristics of viral hepatitis from 2004 to 2023 in Zhejiang Province, China. PLoS One 2025; 20:e0319642. [PMID: 40063651 PMCID: PMC11892861 DOI: 10.1371/journal.pone.0319642] [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: 12/18/2024] [Accepted: 02/05/2025] [Indexed: 05/13/2025] Open
Abstract
BACKGROUND Hepatitis significantly increases the global disease burden and has become a major public health issue worldwide. China is a high-risk area for viral hepatitis, which is also a serious public health problem. METHODS The scaling relationship between various types of hepatitis and population size was explained by a scaling law. Fixed-effects and random-effects meta-analyses were used to calculate a combined index of β based on the single-scale index from 2004 to 2023. Furthermore, the X11 process was employed to identify the structural components of the time series of various types of hepatitis. RESULTS In the past 20 years, the proportion of patients with viral hepatitis in Zhejiang Province has changed significantly, and hepatitis B remains the main type of hepatitis, accounting for approximately 70% of all hepatitis cases. The proportion of hepatitis C and E cases has been increasing, whereas the proportion of hepatitis A cases has been decreasing since 2004 and has remained at a low level (approximately 3%) since 2010. The combined scaling exponents of hepatitis A, hepatitis B, hepatitis C, hepatitis E and unclassified hepatitis based on the random effects model were 0.88 (95% confidence interval(CI): 0.78 to 0.98), 0.78 (95% CI: 0.70 to 0.86), 1.18 (95% CI: 1.11 to 1.26), 0.91 (95% CI: 0.86 to 0.97) and 0.89 (95% CI: 0.79 to 1.00), respectively. CONCLUSION In the past 20 years, the epidemic situation of hepatitis A, hepatitis B and unclassified hepatitis has shown a significant downward trend, whereas the proportions of hepatitis C and hepatitis E among those with viral hepatitis have increased annually. The combined scaling exponent and development trends of the five types of hepatitis show significant heterogeneity. Overall, hepatitis C exhibits superlinear characteristics, whereas other types of hepatitis exhibit sublinear characteristics. Different types of hepatitis exhibit distinct epidemic characteristics and require targeted prevention and control measures.
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Affiliation(s)
- Ming Xue
- Hangzhou Center for Disease Control and Prevention (Hangzhou Health Supervision Institution), Hangzhou, Zhejiang, China
| | - Chen Wu
- Zhejiang Province Center for Disease Control and Prevention, Hangzhou, Zhejiang, China
| | - Kui Liu
- Zhejiang Province Center for Disease Control and Prevention, Hangzhou, Zhejiang, China
| | - Qinbao Lu
- Zhejiang Province Center for Disease Control and Prevention, Hangzhou, Zhejiang, China
| | - Zheyuan Ding
- Zhejiang Province Center for Disease Control and Prevention, Hangzhou, Zhejiang, China
| | - Xinyi Wang
- Zhejiang Province Center for Disease Control and Prevention, Hangzhou, Zhejiang, China
| | - Tianyin Fu
- Zhejiang Province Center for Disease Control and Prevention, Hangzhou, Zhejiang, China
| | - Junfen Lin
- Zhejiang Province Center for Disease Control and Prevention, Hangzhou, Zhejiang, China
| | - Haocheng Wu
- Zhejiang Province Center for Disease Control and Prevention, Hangzhou, Zhejiang, China
- Zhejiang Key Lab of Vaccine, Infectious Disease Prevention and Control, Hangzhou, Zhejiang, China
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Scheibe A, Steingo J, Grace G, Savva H, Sonderup M, Hausler H, Spearman CW. Feasibility of implementing viral hepatitis services into a correctional service facility in Cape Town, South Africa. THE INTERNATIONAL JOURNAL OF DRUG POLICY 2025; 137:104710. [PMID: 39855009 PMCID: PMC11892007 DOI: 10.1016/j.drugpo.2025.104710] [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: 07/14/2024] [Revised: 01/09/2025] [Accepted: 01/11/2025] [Indexed: 01/27/2025]
Abstract
BACKGROUND Hepatitis B virus (HBV) and hepatitis C virus (HCV) are estimated to be of the most prevalent infectious diseases in correctional settings worldwide. However, viral hepatitis services have not been routinely integrated into South African correctional facilities. We aimed to assess prevalence of HBV infection and HCV infection among people accessing HIV services and assess the feasibility of viral hepatitis service integration in a South African correctional centre. METHODS Voluntarily participating people in a correctional services facility were offered free hepatitis B surface antigen (HBsAg) and anti-HCV point-of-care testing in addition to routine HIV testing and treatment services on a first-come, first-served basis during June 2021-March 2022. Off-site laboratory testing (HBV and HCV molecular testing and non-invasive liver fibrosis staging) and screening for hepatocellular carcinoma informed further management. A general practitioner at the facility managed participants, with virtual support from hepatologists. Data on age and history of injecting was collected and point-of-care and laboratory results were recorded. Data were analysed using descriptive statistics. RESULTS The median age of the 765 people who participated was 32.5 years (IQR 27.5 - 38.2), with 2.2% (17/765) reporting having ever injected a drug. The sample prevalence was 3.9% (30/765) for HBV infection, 0.5% (3/665) for HCV infection, and 1.2% (9/765) for HIV-HBV coinfection. Thirty people had reactive HBsAg point-of-care tests. Among those with reactive HBsAg point-of-care tests 90.0% (27/30) received work-up, among whom 48.1% (13/27) were monitored, 44.4% (12/27) were placed on treatment and two people were released before a management plan could be finalised. Of those treated 33.3% (4/12) started tenofovir/emtricitabine and 66.7% (8/12) antiretroviral therapy. Of the eligible participants, 27.3% (201/735) received at least one hepatitis B vaccine dose and 26.9% (54/201) received three doses. All three participants who had confirmed HCV infection were started on direct-acting antivirals. Of the two completing treatment one achieved sustained virological response at 12 weeks (SVR12), one person was released before SVR12 was done. One person was lost to follow-up. No clinical adverse events were reported. CONCLUSION There was a notable viral hepatitis burden among people in this correctional centre and integration of viral hepatitis services into the existing HIV services was acceptable and feasible. Further efforts to sustain and expand access to viral hepatitis services in South African correctional centres could catalyse national viral hepatitis elimination efforts.
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Affiliation(s)
- Andrew Scheibe
- TB HIV Care, 7th Floor, 11 Adderley Street City Centre, Cape Town 8001, South Africa; Community Oriented Primary Care Research Unit, Department of Family Medicine, University of Pretoria, 31 Bophelo Road, Gezina, Pretoria, 0084, South Africa.
| | - Joel Steingo
- TB HIV Care, 7th Floor, 11 Adderley Street City Centre, Cape Town 8001, South Africa.
| | - Gaynor Grace
- Department of Correctional Services, Goodwood Correctional Centre, Peninsula Drive, Monte Vista, 7460, South Africa.
| | - Helen Savva
- United States Centers for Disease Control and Prevention, Division of Global HIV and TB, 100 Totius St, Groenkloof, Pretoria, 0027, South Africa.
| | - Mark Sonderup
- Division of Hepatology, Department of Medicine, Faculty of Health Sciences, University of Cape Town and Groote Schuur Hospital, Main Road, Observatory, Cape Town, South Africa.
| | - Harry Hausler
- TB HIV Care, 7th Floor, 11 Adderley Street City Centre, Cape Town 8001, South Africa; Community Oriented Primary Care Research Unit, Department of Family Medicine, University of Pretoria, 31 Bophelo Road, Gezina, Pretoria, 0084, South Africa.
| | - C Wendy Spearman
- Division of Hepatology, Department of Medicine, Faculty of Health Sciences, University of Cape Town and Groote Schuur Hospital, Main Road, Observatory, Cape Town, South Africa.
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Yuan X, Zhou M, Liu X, Fan J, Chen L, Luo J, Li S, Zhou L. Identification of Biomarkers for Response to Interferon in Chronic Hepatitis B Based on Bioinformatics Analysis and Machine Learning. Viral Immunol 2025; 38:61-69. [PMID: 39992204 DOI: 10.1089/vim.2024.0091] [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
Interferon (IFN) is a pivotal agent against hepatitis B virus (HBV) in clinic, but there is a lack of accurate biomarkers to predict the response to IFN therapy in patients with chronic hepatitis B (CHB). Our study aimed to investigate potential targets for IFN therapy and to explore the network of interactions associated with IFN response. MicroRNA (miRNA) (GSE29911) and messenger RNA (GSE27555) datasets were used to screen the differentially expressed miRNAs (DEmiRNAs) and differentially expressed genes (DEGs). The random forest and k-nearest neighbors algorithm were used to further screen the core DEmiRNAs and build a prediction model. A Protein-Protein Interaction (PPI) network based on the STRING database was constructed and visualized by the Cytoscape software. Then, we collected transcription factors (TFs) from the TransmiR database to construct the TF-miRNA-hub gene regulatory network. Finally, real-time quantitative polymerase chain reaction was used to verify the expression of four miRNAs in HepG2-NTCP and Huh-7, and the effect of IFN treatment on four miRNAs' expression was preliminarily explored. Eighteen DEmiRNAs in GSE29911 and 700 DEGs in GSE27555 were identified. Boruta feature selection identified four miRNAs (miR-873, miR-200a, miR-30b, and let-7g) from 18 DEmiRNAs. We identified 48 TFs, 4 miRNAs, and 10 hub genes and constructed a TF-miRNA-hub gene network to suggest the mechanism of IFN response. According to the experimental results, miR-873 was upregulated and IFN treatment could inhibit it in HBV-transfected cells (p < 0.05). We constructed a TF-miRNA-hub gene regulatory network, and our results demonstrate that miR-873 was identified as a potential biomarker of IFN response in patients with CHB. This information provides an initial basis for understanding the complex IFN response regulatory mechanisms.
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Affiliation(s)
- Xiaoqin Yuan
- Department of Epidemiology, School of Public Health, Chongqing Medical University, Chongqing, China
| | - Mingsha Zhou
- Chongqing Hospital of The First Affiliated Hospital of Guangzhou University of Chinese Medicine (Chongqing Beibei Hospital of Traditional Chinese Medicine), Medical Records and Statistics Department, Chongqing, China
| | - Xing Liu
- Jiulongpo District Center for Disease Control and Prevention, Immunization Planning Department, Chongqing, China
| | - Jie Fan
- Chongqing Medical and Pharmaceutical College, School of Public Health and Emergency Management, Chongqing, China
| | - Lijuan Chen
- Department of Epidemiology, School of Public Health, Chongqing Medical University, Chongqing, China
| | - Jia Luo
- Department of Epidemiology, School of Public Health, Chongqing Medical University, Chongqing, China
| | - Shan Li
- Department of Epidemiology, School of Public Health, Chongqing Medical University, Chongqing, China
| | - Li Zhou
- Department of Epidemiology, School of Public Health, Chongqing Medical University, Chongqing, China
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Wembulua BS, Le Gal F, Ndiaye O, Pandi MS, Akotia MK, Badiane AS, Hamouda P, Tine J, Ndiaye K, Béguelin C, Ngom NF, Wandeler G, Seydi M, Mena AR, SEN‐B. Hepatitis Delta and Liver Disease Among People Living With Hepatitis B With or Without HIV Co-Infection in Senegal. Liver Int 2025; 45:e70026. [PMID: 39967446 PMCID: PMC11836594 DOI: 10.1111/liv.70026] [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: 09/26/2024] [Revised: 01/08/2025] [Accepted: 02/04/2025] [Indexed: 02/20/2025]
Abstract
BACKGROUND AND AIMS The prevalence of hepatitis delta virus (HDV) infection among persons living with hepatitis B virus (HBV) and its impact on liver-related complications in West Africa are ill-defined. Wetested a large urban HBV cohort in Senegal for the presence of HDV/HBV co-infection and evaluated its association with liver fibrosis. METHODS We included persons with positive hepatitis B surface antigen (HBsAg) enrolled in the SEN-B cohort since 2019. Anti-HDV antibodies (HDVAb) were tested using the Anti-HD Diasorin LiaisonXL test, HDV RNA was measured with RT-qPCR and genotyping was determined through sequencing. We used multivariable logistic regression to evaluate the association between HDVAb positivity and liver fibrosis, defined as a liver stiffness measurement > 7.0 kPa. RESULTS We analysed 914 individuals with a median age of 32 years (interquartile range [IQR] 26-41), of whom 487 (53.3%) were men and 117 (12.8%) had HIV co-infection. Thirteen participants (1.4%, 95% CI 0.8-2.4) had a positive HDVAb test, of whom 8/13 (61.5%) showed detectable HDV RNA. HDV genotype 5 was found in 75.0% of cases. In multivariable analyses, HDVAb positivity (aOR 11.7, 95% CI 3.1-45.7), male sex (aOR 5.4, 95% CI 3.1-10.3), ALT > 40 IU/L (aOR 4.4, 95% CI 2.4-8.2) and HBeAg positivity (aOR 4.6, 95% CI 1.8-11.9) were independently associated with liver fibrosis. CONCLUSION The prevalence of HDV infection was low in persons living with HBV in Dakar, but those affected had a very high risk of presenting with liver cirrhosis. Efforts to improve HDV screening and management are urgently needed in Senegal.
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Affiliation(s)
| | - Fredéric Le Gal
- Centre National de Référence des Hépatites Virales B, C et Delta, Laboratoire de Microbiologie clinique, Hôpital Avicenne, Assistance Publique Hôpitaux de ParisSorbonne Université, Paris CitéBobignyFrance
| | - Ousseynou Ndiaye
- Centre Régional de Recherche et Formation Clinique à la Prise en Charge de FannFann University HospitalDakarSenegal
| | - Melissa Sandrine Pandi
- Centre Régional de Recherche et Formation Clinique à la Prise en Charge de FannFann University HospitalDakarSenegal
- Doctoral School of Life Sciences, Health, and EnvironmentCheikh Anta Diop University of DakarDakarSenegal
| | - Messan Kodzo Akotia
- Centre Régional de Recherche et Formation Clinique à la Prise en Charge de FannFann University HospitalDakarSenegal
| | - Aboubakar Sidick Badiane
- Centre Régional de Recherche et Formation Clinique à la Prise en Charge de FannFann University HospitalDakarSenegal
| | - Poussyina Hamouda
- Centre National de Référence des Hépatites Virales B, C et Delta, Laboratoire de Microbiologie clinique, Hôpital Avicenne, Assistance Publique Hôpitaux de ParisSorbonne Université, Paris CitéBobignyFrance
| | - Judicaël Tine
- Service de Maladies Infectieuses et TropicalesFann University HospitalDakarSenegal
| | - Kiné Ndiaye
- Centre de Traitement Ambulatoire de FannFann University HospitalDakarSenegal
| | - Charles Béguelin
- Department of Infectious DiseasesBern University Hospital, University of BernBernSwitzerland
| | - Ndeye Fatou Ngom
- Centre de Traitement Ambulatoire de FannFann University HospitalDakarSenegal
| | - Gilles Wandeler
- Service de Maladies Infectieuses et TropicalesFann University HospitalDakarSenegal
- Department of Infectious DiseasesBern University Hospital, University of BernBernSwitzerland
- Institute of Social and Preventive MedicineUniversity of BernBernSwitzerland
| | - Moussa Seydi
- Service de Maladies Infectieuses et TropicalesFann University HospitalDakarSenegal
| | - Adrià Ramírez Mena
- Service de Maladies Infectieuses et TropicalesFann University HospitalDakarSenegal
- Department of Infectious DiseasesBern University Hospital, University of BernBernSwitzerland
- Graduate School of Health SciencesUniversity of BernBernSwitzerland
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Larsen PP, Dinet V, Delcourt C, Helmer C, Linard M. Could Infectious Agents Play a Role in the Onset of Age-related Macular Degeneration? A Scoping Review. OPHTHALMOLOGY SCIENCE 2025; 5:100668. [PMID: 39906411 PMCID: PMC11791433 DOI: 10.1016/j.xops.2024.100668] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 08/29/2024] [Revised: 11/19/2024] [Accepted: 11/25/2024] [Indexed: 02/06/2025]
Abstract
Topic This scoping review aims to summarize the current state of knowledge on the potential involvement of infections in age-related macular degeneration (AMD). Clinical relevance Age-related macular degeneration is a multifactorial disease and the leading cause of vision loss among older adults in developed countries. Clarifying whether certain infections participate in its onset or progression seems essential, given the potential implications for treatment and prevention. Methods Using the PubMed database, we searched for articles in English, published until June 1, 2023, whose title and/or abstract contained terms related to AMD and infections. All types of study design, infectious agents, AMD diagnostic methods, and AMD stages were considered. Articles dealing with the oral and gut microbiota were not included but we provide a brief summary of high-quality literature reviews recently published on the subject. Results Two investigators independently screened the 868 articles obtained by our algorithm and the reference lists of selected studies. In total, 40 articles were included, among which 30 on human data, 9 animal studies, 6 in vitro experiments, and 1 hypothesis paper (sometimes with several data types in the same article). Of these, 27 studies were published after 2010, highlighting a growing interest in recent years. A wide range of infectious agents has been investigated, including various microbiota (nasal, pharyngeal), 8 bacteria, 6 viral species, and 1 yeast. Among them, most have been investigated anecdotally. Only Chlamydia pneumoniae, Cytomegalovirus, and hepatitis B virus received more attention with 17, 6, and 4 studies, respectively. Numerous potential pathophysiological mechanisms have been discussed, including (1) an indirect role of infectious agents (i.e. a role of infections located distant from the eye, mainly through their interactions with the immune system) and (2) a direct role of some infectious agents implying potential infection of various cells types within AMD-related tissues. Conclusions Overall, this review highlights the diversity of possible interactions between infectious agents and AMD and suggests avenues of research to enrich the data currently available, which provide an insufficient level of evidence to conclude whether or not infectious agents are involved in this pathology. Financial Disclosures Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
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Affiliation(s)
- Petra P. Larsen
- University of Bordeaux, INSERM, BPH, U1219, Bordeaux, France
| | - Virginie Dinet
- INSERM, Biologie des Maladies Cardiovasculaires, U1034, University of Bordeaux, Pessac, France
| | - Cécile Delcourt
- University of Bordeaux, INSERM, BPH, U1219, Bordeaux, France
| | | | - Morgane Linard
- University of Bordeaux, INSERM, BPH, U1219, Bordeaux, France
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Xie Y, Liu F, Wu Y, Zhu Y, Jiang Y, Wu Q, Dong Z, Liu K. Inflammation in cancer: therapeutic opportunities from new insights. Mol Cancer 2025; 24:51. [PMID: 39994787 PMCID: PMC11849313 DOI: 10.1186/s12943-025-02243-8] [Citation(s) in RCA: 7] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2024] [Accepted: 01/20/2025] [Indexed: 02/26/2025] Open
Abstract
As one part of the innate immune response to external stimuli, chronic inflammation increases the risk of various cancers, and tumor-promoting inflammation is considered one of the enabling characteristics of cancer development. Recently, there has been growing evidence on the role of anti-inflammation therapy in cancer prevention and treatment. And researchers have already achieved several noteworthy outcomes. In the review, we explored the underlying mechanisms by which inflammation affects the occurrence and development of cancer. The pro- or anti-tumor effects of these inflammatory factors such as interleukin, interferon, chemokine, inflammasome, and extracellular matrix are discussed. Since FDA-approved anti-inflammation drugs like aspirin show obvious anti-tumor effects, these drugs have unique advantages due to their relatively fewer side effects with long-term use compared to chemotherapy drugs. The characteristics make them promising candidates for cancer chemoprevention. Overall, this review discusses the role of these inflammatory molecules in carcinogenesis of cancer and new inflammation molecules-directed therapeutic opportunities, ranging from cytokine inhibitors/agonists, inflammasome inhibitors, some inhibitors that have already been or are expected to be applied in clinical practice, as well as recent discoveries of the anti-tumor effect of non-steroidal anti-inflammatory drugs and steroidal anti-inflammatory drugs. The advantages and disadvantages of their application in cancer chemoprevention are also discussed.
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Affiliation(s)
- Yifei Xie
- Department of Pathology and Forensic Medicine, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, 450000, China
- State Key Laboratory of Metabolic Dysregulation & the Prevention and Treatment of Esophageal Cancer, Zhengzhou, Henan, 450052, China
- The Collaborative Innovation Center of Henan Province for Cancer Chemoprevention, Zhengzhou, Henan, 450001, China
| | - Fangfang Liu
- State Key Laboratory of Metabolic Dysregulation & the Prevention and Treatment of Esophageal Cancer, Zhengzhou, Henan, 450052, China
- Department of Medical Genetics and Cell Biology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, 450000, China
- China-US (Henan) Hormel Cancer Institute, Zhengzhou, Henan, 450007, China
- The Collaborative Innovation Center of Henan Province for Cancer Chemoprevention, Zhengzhou, Henan, 450001, China
| | - Yunfei Wu
- State Key Laboratory of Metabolic Dysregulation & the Prevention and Treatment of Esophageal Cancer, Zhengzhou, Henan, 450052, China
- Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, 450000, China
| | - Yuer Zhu
- State Key Laboratory of Metabolic Dysregulation & the Prevention and Treatment of Esophageal Cancer, Zhengzhou, Henan, 450052, China
- Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, 450000, China
| | - Yanan Jiang
- State Key Laboratory of Metabolic Dysregulation & the Prevention and Treatment of Esophageal Cancer, Zhengzhou, Henan, 450052, China
- Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, 450000, China
- China-US (Henan) Hormel Cancer Institute, Zhengzhou, Henan, 450007, China
- The Collaborative Innovation Center of Henan Province for Cancer Chemoprevention, Zhengzhou, Henan, 450001, China
| | - Qiong Wu
- State Key Laboratory of Metabolic Dysregulation & the Prevention and Treatment of Esophageal Cancer, Zhengzhou, Henan, 450052, China
- Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, 450000, China
- China-US (Henan) Hormel Cancer Institute, Zhengzhou, Henan, 450007, China
- The Collaborative Innovation Center of Henan Province for Cancer Chemoprevention, Zhengzhou, Henan, 450001, China
| | - Zigang Dong
- State Key Laboratory of Metabolic Dysregulation & the Prevention and Treatment of Esophageal Cancer, Zhengzhou, Henan, 450052, China.
- Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, 450000, China.
- China-US (Henan) Hormel Cancer Institute, Zhengzhou, Henan, 450007, China.
- The Collaborative Innovation Center of Henan Province for Cancer Chemoprevention, Zhengzhou, Henan, 450001, China.
| | - Kangdong Liu
- State Key Laboratory of Metabolic Dysregulation & the Prevention and Treatment of Esophageal Cancer, Zhengzhou, Henan, 450052, China.
- Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, 450000, China.
- China-US (Henan) Hormel Cancer Institute, Zhengzhou, Henan, 450007, China.
- The Collaborative Innovation Center of Henan Province for Cancer Chemoprevention, Zhengzhou, Henan, 450001, China.
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Pavlova A, Fan Z, Lynch DL, Gumbart JC. Machine learning of molecular dynamics simulations provides insights into modulation of viral capsid assembly. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2025:2025.02.07.637202. [PMID: 39974933 PMCID: PMC11839048 DOI: 10.1101/2025.02.07.637202] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 02/21/2025]
Abstract
An effective approach in the development of novel antivirals is to target the assembly of viral capsids using capsid assembly modulators (CAMs). CAMs targeting hepatitis B virus (HBV) have two major modes of function: they can either accelerate nucleocapsid assembly, retaining its structure, or misdirect it into non-capsid-like particles. Previous molecular dynamics (MD) simulations of early capsid-assembly intermediates showed differences in protein conformations for apo and bound states. Here, we have developed and tested several classification machine learning (ML) models to better distinguish between apo-tetramer intermediates and those bound to accelerating or misdirecting CAMs. Models based on tertiary structural properties of the Cp149 tetramers and their inter-dimer orientation, as well as models based on direct and inverse contact distances between protein residues, were tested. All models distinguished the apo states and the two CAM-bound states with high accuracy. Furthermore, tertiary structure models and residue-distance models highlighted different tetramer regions as important for classification. Both models can be used to better understand structural transitions that govern the assembly of nucleocapsids and to assist the development of more potent CAMs. Finally, we demonstrate the utility of classification ML methods in comparing MD trajectories and describe our ML approaches, which can be extended to other systems of interest.
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Affiliation(s)
- Anna Pavlova
- School of Physics, Georgia Institute of Technology, Atlanta, GA, 30332 USA
| | - Zixing Fan
- Interdisciplinary Bioengineering Graduate Program, Georgia Institute of Technology, Atlanta, GA, 30332 USA
| | - Diane L Lynch
- School of Physics, Georgia Institute of Technology, Atlanta, GA, 30332 USA
| | - James C Gumbart
- School of Physics, Georgia Institute of Technology, Atlanta, GA, 30332 USA
- School of Chemistry & Biochemistry, Georgia Institute of Technology, Atlanta, GA, 30332 USA
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Gan C, Yuan Y, Shen H, Gao J, Kong X, Che Z, Guo Y, Wang H, Dong E, Xiao J. Liver diseases: epidemiology, causes, trends and predictions. Signal Transduct Target Ther 2025; 10:33. [PMID: 39904973 PMCID: PMC11794951 DOI: 10.1038/s41392-024-02072-z] [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: 06/30/2024] [Revised: 10/06/2024] [Accepted: 11/12/2024] [Indexed: 02/06/2025] Open
Abstract
As a highly complex organ with digestive, endocrine, and immune-regulatory functions, the liver is pivotal in maintaining physiological homeostasis through its roles in metabolism, detoxification, and immune response. Various factors including viruses, alcohol, metabolites, toxins, and other pathogenic agents can compromise liver function, leading to acute or chronic injury that may progress to end-stage liver diseases. While sharing common features, liver diseases exhibit distinct pathophysiological, clinical, and therapeutic profiles. Currently, liver diseases contribute to approximately 2 million deaths globally each year, imposing significant economic and social burdens worldwide. However, there is no cure for many kinds of liver diseases, partly due to a lack of thorough understanding of the development of these liver diseases. Therefore, this review provides a comprehensive examination of the epidemiology and characteristics of liver diseases, covering a spectrum from acute and chronic conditions to end-stage manifestations. We also highlight the multifaceted mechanisms underlying the initiation and progression of liver diseases, spanning molecular and cellular levels to organ networks. Additionally, this review offers updates on innovative diagnostic techniques, current treatments, and potential therapeutic targets presently under clinical evaluation. Recent advances in understanding the pathogenesis of liver diseases hold critical implications and translational value for the development of novel therapeutic strategies.
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Affiliation(s)
- Can Gan
- Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, China
| | - Yuan Yuan
- Aier Institute of Ophthalmology, Central South University, Changsha, China
| | - Haiyuan Shen
- Department of Oncology, the First Affiliated Hospital; The Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Anhui Medical University, Hefei, China
| | - Jinhang Gao
- Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, China
| | - Xiangxin Kong
- Engineering and Translational Medicine, Medical College, Tianjin University, Tianjin, China
| | - Zhaodi Che
- Clinical Medicine Research Institute and Department of Anesthesiology, The First Affiliated Hospital of Jinan University, Guangzhou, China
| | - Yangkun Guo
- Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, China
| | - Hua Wang
- Department of Oncology, the First Affiliated Hospital; The Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Anhui Medical University, Hefei, China.
| | - Erdan Dong
- Research Center for Cardiopulmonary Rehabilitation, University of Health and Rehabilitation Sciences Qingdao Hospital, School of Health and Life Sciences, University of Health and Rehabilitation Sciences, Qingdao, China.
- Department of Cardiology and Institute of Vascular Medicine, Peking University Third Hospital, State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing, China.
| | - Jia Xiao
- Clinical Medicine Research Institute and Department of Anesthesiology, The First Affiliated Hospital of Jinan University, Guangzhou, China.
- Department of Gastroenterology, Qingdao Central Hospital, University of Health and Rehabilitation Sciences, Qingdao, China.
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Li F, Qu L, Liu Y, Wu X, Qi X, Wang J, Zhu H, Yang F, Shen Z, Guo Y, Zhang Y, Yu J, Mao R, Zhang Q, Zhang F, Chen L, Huang Y, Zhang X, Li Q, Zhang W, Zhang J. PegIFN alpha-2a reduces relapse in HBeAg-negative patients after nucleo(s)tide analogue cessation: A randomized-controlled trial. J Hepatol 2025; 82:211-221. [PMID: 39094743 DOI: 10.1016/j.jhep.2024.07.019] [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: 01/15/2024] [Revised: 07/17/2024] [Accepted: 07/22/2024] [Indexed: 08/04/2024]
Abstract
BACKGROUND & AIMS Nucleo(s)tide analogue (NUC) cessation can lead to hepatitis B surface antigen (HBsAg) clearance but also a high rate of virological relapse. However, the effect of pegylated interferon alpha-2a (PegIFN-α-2a) on virological relapse after NUC cessation is unknown. Therefore, this study aimed to evaluate the effect of switching from NUC to PegIFN-α-2a treatment for 48 weeks on virological relapse up to week 96. METHODS In this multicenter randomized-controlled clinical trial, 180 non-cirrhotic patients with HBeAg-negative chronic hepatitis B on continuous NUC therapy for ≥2.5 years, with HBV DNA levels <60 IU/ml, were randomized to discontinue NUC therapy (n = 90) or receive 48 weeks of PegIFN-α-2a treatment (n = 90). Patients were followed up for up to 96 weeks. The primary endpoint was the virological relapse rate up to week 96. RESULTS Intention-to-treat analysis revealed patients in the interferon monotherapy group had significantly lower cumulative virological relapse rates than the NUC cessation group until week 96 (20.8% vs. 53.6%, p <0.0001). Consistently, a significantly lower proportion of patients in the interferon monotherapy group had virological relapse than those in the NUC cessation group at 48 weeks off treatment (17.8% vs. 36.7%, p = 0.007). The virological relapse rate positively correlated with HBsAg levels in the NUC cessation group. The interferon monotherapy group had a lower cumulative clinical relapse rate (7.8% vs. 20.9%, p = 0.008) and a higher HBsAg loss rate (21.5% vs. 9.0%, p = 0.03) than the NUC cessation group. CONCLUSIONS Switching from NUC to PegIFN-α-2a treatment for 48 weeks significantly reduces virological relapse rates and leads to higher HBsAg loss rates than NUC treatment cessation alone in patients with HBeAg-negative chronic hepatitis B. IMPACT AND IMPLICATIONS Nucleo(s)tide analogue (NUC) cessation can lead to HBsAg clearance but also a high rate of virological relapse, but an optimized scheme to reduce the virological relapse rate after NUC withdrawal is yet to be reported. This randomized-controlled trial investigated the effect of switching from NUC to PegIFN-α-2a treatment for 48 weeks on virological relapse up to week 96 in patients with HBeAg-negative chronic hepatitis B. The interferon monotherapy group had a significantly lower cumulative virological relapse rate (20.8% vs. 53.6%, p <0.0001) and higher HBsAg loss rate (21.5% vs. 9.0%, p = 0.03) than the NUC cessation group up to week 96. This provides an optimized strategy for NUC cessation in HBeAg-negative patients. TRIAL REGISTRATION NUMBER NCT02594293.
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Affiliation(s)
- Fahong Li
- Department of Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, Shanghai Institute of Infectious Diseases and Biosecurity, National Medical Center for Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China
| | - Lihong Qu
- Department of Infectious Disease, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China
| | - Yanhong Liu
- Department of Infectious Diseases, Tongren hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Xiaoping Wu
- Department of Infectious Diseases, The First Affiliated Hospital of Nanchang University, Jiangxi, China
| | - Xun Qi
- Department of Hepatology, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China
| | - Jinyu Wang
- Department of Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, Shanghai Institute of Infectious Diseases and Biosecurity, National Medical Center for Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China
| | - Haoxiang Zhu
- Department of Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, Shanghai Institute of Infectious Diseases and Biosecurity, National Medical Center for Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China
| | - Feifei Yang
- Department of Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, Shanghai Institute of Infectious Diseases and Biosecurity, National Medical Center for Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China
| | - Zhongliang Shen
- Department of Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, Shanghai Institute of Infectious Diseases and Biosecurity, National Medical Center for Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China
| | - Yifei Guo
- Department of Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, Shanghai Institute of Infectious Diseases and Biosecurity, National Medical Center for Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China
| | - Yongmei Zhang
- Department of Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, Shanghai Institute of Infectious Diseases and Biosecurity, National Medical Center for Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China
| | - Jie Yu
- Department of Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, Shanghai Institute of Infectious Diseases and Biosecurity, National Medical Center for Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China
| | - Richeng Mao
- Department of Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, Shanghai Institute of Infectious Diseases and Biosecurity, National Medical Center for Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China
| | - Qiran Zhang
- Department of Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, Shanghai Institute of Infectious Diseases and Biosecurity, National Medical Center for Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China
| | - Fengdi Zhang
- Department of Infectious Disease, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China
| | - Liang Chen
- Department of Hepatology, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China
| | - Yuxian Huang
- Department of Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, Shanghai Institute of Infectious Diseases and Biosecurity, National Medical Center for Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China.
| | - Xinxin Zhang
- Department of Infectious Diseases, Research Laboratory of Clinical Virology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
| | - Qingxing Li
- Department of Infectious Diseases, The 1st Affiliated Hospital of Wenzhou Medical University, Wenzhou Medical University, Nanbaixiang, Ouhai District, Wenzhou, 325003, China.
| | - Wenhong Zhang
- Department of Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, Shanghai Institute of Infectious Diseases and Biosecurity, 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, Shanghai Institute of Infectious Diseases and Biosecurity, National Medical Center for Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China; Department of Infectious Diseases, Jing'An Branch of Huashan Hospital, Fudan University, Shanghai, China.
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Heiat M, Javanbakht M, Jafari D, Poudineh M, Heydari F, Sharafi H, Alavian SM. Correlation of IL-10 and IL18 with the development of liver cirrhosis associated with hepatitis B virus infection: A systematic review. Cytokine 2025; 186:156818. [PMID: 39671883 DOI: 10.1016/j.cyto.2024.156818] [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: 07/01/2024] [Revised: 10/02/2024] [Accepted: 11/16/2024] [Indexed: 12/15/2024]
Abstract
BACKGROUND Patients who have been infected with the Hepatitis B virus (HBV) are susceptible to developing liver cirrhosis (LC) and hepatocellular carcinoma (HCC). The objective of this systematic review was to comprehensively scrutinize the existing evidence concerning the association between host genetic polymorphisms and HBV-associated LC. METHODS We searched databases of PubMed, Scopus, and Web of Science for relevant articles published from building databases to 25 October 2023. RESULT We detected 104 relevant articles, relating to 84 individuals genes. Nine genes had the strong evidence of correlation, including IL-10, IL-18, IL-1B, TGF- β, TLR3, STAT4, IL-1RN, Tim3, and IFN receptors. A positive correlation was found for 33 genes but this data had not yet been replicated, 11 genes had limited or mixed evidence of a correlation, and 34 genes indicated no correlation. IL-10 and IL-18 had the most evidence of correlation. There was a notable amount of diversity in both the design and method of studies and data quality. CONCLUSION IL-10 and IL-18 had the most evidence of correlation. There was a notable amount of diversity in both the design and method of studies and data quality. It is of necessary to take into account the fundamental mechanism behind these associations and discern those that are confounded by the coexistence of other LC/HCC risk factors and response to therapy. These results are expected to guide future studies on the genetic susceptibility of HBV-related LC/HCC.
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Affiliation(s)
- Mohammad Heiat
- Baqiyatallah Research Center for Gastroenterology and Liver Diseases (BRCGL), Clinical Sciences Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran.
| | - Mohammad Javanbakht
- Nephrology and Urology Research Center, Clinical Science Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran
| | - Davood Jafari
- Department of Immunology, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran
| | - Mohadeseh Poudineh
- Student Research Committee, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran
| | - Fatemeh Heydari
- Student Research Committee, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran
| | | | - Seyed Moayed Alavian
- Baqiyatallah Research Center for Gastroenterology and Liver Diseases (BRCGL), Clinical Sciences Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran
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Wang H, Wang J, Zhang S, Zhang S, Zhang Z, Liu J, Pan Y, Jiang C, Xiong Y, Fan T, Huang R, Li L. Clinical Features and Transition of Acute Hepatitis B Virus Infection. J Viral Hepat 2025; 32:e14048. [PMID: 39729036 DOI: 10.1111/jvh.14048] [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: 06/03/2024] [Revised: 11/18/2024] [Accepted: 11/30/2024] [Indexed: 12/28/2024]
Abstract
Acute hepatitis B (AHB) is generally a self-limiting illness in adults and most patients achieve hepatitis B surface antigen (HBsAg) clearance within 6 months. We aimed to investigate the proportion and influencing factors of chronic outcome in adult AHB patients. A total of 126 consecutive AHB patients were included between January 2013 and October 2018. Multivariate regression analysis was conducted to evaluate the influencing factor of HBsAg clearance. Fourteen (11.1%) patients failed to achieve HBsAg clearance within 6 months. Among them, nine patients achieved HBsAg clearance within 6-12 months, while five patients had persistent HBsAg positive over 1 year. Patients with HBsAg clearance had lower baseline antibody to hepatitis B core antigen (anti-HBc) (7.0 S/CO vs. 8.0 S/CO, p = 0.090) and HBsAg levels than those with chronicity of AHB. Multivariate analysis revealed that HBsAg ≤ 250 IU/mL (HR 3.008, IQR 1.877, 4.820, p < 0.001) and anti-HBc levels (HR 0.830, IQR 0.755, 0.912, p < 0.001) was significantly associated with HBsAg clearance. Anti-HBc remained an independent predictor of HBsAg clearance in different HBsAg subgroups. Patients with HBsAg > 250 IU/mL (p < 0.001) and high anti-HBc (p = 0.001) had lower cumulative HBsAg clearance rates than those with low HBsAg and anti-HBc. 11.1% of AHB patients did not achieve HBsAg clearance within 6 months, while the proportion of patients with persistent HBsAg positive decreased to 4.0% after 1 year. Combination of baseline HBsAg and anti-HBc levels could identify patients who might have a possible risk of chronicity following AHB.
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Affiliation(s)
- Huali Wang
- Department of General Practice, Nanjing Second Hospital, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
| | - Jian Wang
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China
- Institute of Viruses and Infectious Diseases, Nanjing University, Nanjing, Jiangsu, China
| | - Shaoqiu Zhang
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China
| | - Shuai Zhang
- Department of General Practice, Nanjing Second Hospital, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
| | - Zhiyi Zhang
- Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
| | - Jiacheng Liu
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China
| | - Yifan Pan
- Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, Jiangsu, China
| | - Chao Jiang
- Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Jiangsu University, Nanjing, Jiangsu, China
| | - Ye Xiong
- Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
| | - Tao Fan
- Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
| | - Rui Huang
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China
- Institute of Viruses and Infectious Diseases, Nanjing University, Nanjing, Jiangsu, China
| | - Li Li
- Department of Hepatology, Nanjing Second Hospital, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
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Jaldo MM, Joffe MW, Zemedkun ES. Prevalence of hepatitis B virus and associated factors among blood donors in Hossana blood bank catchment area, Southern Ethiopia. BMC Infect Dis 2025; 25:143. [PMID: 39885394 PMCID: PMC11783898 DOI: 10.1186/s12879-025-10550-0] [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: 10/05/2024] [Accepted: 01/23/2025] [Indexed: 02/01/2025] Open
Abstract
BACKGROUND Human hepatitis is an inflammation of the liver brought on by the DNA virus known as the hepatitis B virus (HBV). Around the world, 240 million people are thought to have HBV in a chronic state. The prevalence of viral hepatitis is extremely high in Africa. Prior reports from various regions of the nation have indicated a variable prevalence of HBV infection. OBJECTIVE To estimate the prevalence of HBV infections and associated factors among blood donors in the Hossana blood bank catchment area in August 2023. METHODS A community-based cross-sectional study design was conducted among 546 blood donors in the Hossana blood bank catchment area from August 22 to September 22, 2023. Study participants were included using the system established by the blood bank. Both Binary and multivariable logistic regression analysis was conducted. The association of variables was declared at p-value < 0.05 and strength of association was presented using AOR with a corresponding 95% CI. The adequacy of the model was checked by Hosmer-Lemeshow test. RESULTS a total of 546 participant's data was analyzed. The prevalence of HBV among blood donors in the Hossana blood bank catchment area was 7.88 with 95% CI [5.76-10.46]. No participants received post-donation counseling. Having multiple sexual partners (AOR = 5.18, 95% CI: 1.32-20.36), Sharing of sharp material (AOR = 3.66, 95% CI: 1.32-10.13) and tooth extraction (AOR = 5.55, 95% CI: 2.08-14.78) were identified as factors associated with HBV positivity. CONCLUSION In this study, the prevalence of hepatitis B virus was 7.88, which is intermediate. Multiple sexual partners, sharing of sharp material, and tooth extraction were related to the hepatitis b virus. Though post-donation counseling is important for the control and prevention of hepatitis b virus infection, it has been neglected since the establishment of the blood bank we strongly recommend counseling regular donors. CLINICAL TRIAL NUMBER Not applicable.
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Affiliation(s)
- Mesfin Menza Jaldo
- School of Public Health, College of Medicine and Health Sciences, Wachemo University, Hossana, Ethiopia.
| | | | - Eyasu Samuel Zemedkun
- School of Medicine, College of Medicine and Health Sciences, Wachemo University, Hossana, Ethiopia
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Moonen CPB, Brouwers EEHG, Hoebe CJPA, Dukers-Muijrers NHTM, Bouchaara J, van Loo IHM, den Heijer CDJ. Reaching Syrian migrants through Dutch municipal registries for hepatitis B and C point-of-care testing. PLoS One 2025; 20:e0316726. [PMID: 39823486 PMCID: PMC11741604 DOI: 10.1371/journal.pone.0316726] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2023] [Accepted: 12/13/2024] [Indexed: 01/19/2025] Open
Abstract
Undetected chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infections can lead to cirrhosis and liver cancer. Syrian migrants are the largest non-European migrant group in the Netherlands with HBV and HCV prevalence rates above 2%. This study aimed to reach Syrian migrants for HBV and HCV testing using point-of-care tests (POCT). A multifaceted strategy was employed to reach Syrian migrants aged ≥16 years from two Dutch municipalities for free-of-charge HBsAg and anti-HCV POCT using finger prick blood at the regional Public Health Service. All were personally invited by the Public Health Service by postal mail, based on municipal registry data. Respondents' medical history data were analysed descriptively and data on age, sex, and municipality were compared with non-participating invitees, using Pearson's Chi-square test. Of the study population (N = 832), 32.3% (n = 269) attended the testing. The mean age of participants was 36 years (range 16-70), 59.1% were men, and 66.5% were unemployed. Non-participation was higher in the younger age groups (<30 years) (p < .001). The POCT using finger prick blood was well received. None tested HBsAg or anti-HCV positive. With approximately one-third of participation, this study demonstrated relatively high reach of Syrian migrants for testing, compared to studies with similar recruitment methods. However, while the reach could be considered successful, testing failed to demonstrate new infection in this key population. Thereby, other methods may be preferred to identify new HBV and HCV infections, such as opportunistic testing within existing care processes.
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Affiliation(s)
- Chrissy P. B. Moonen
- Department of Sexual Health, Infectious Diseases and Environmental Health, Living Lab Public Health, South Limburg Public Health Service, Heerlen, The Netherlands
- Department of Social Medicine, Care and Public Health Research Institute (CAPHRI), Maastricht University, Maastricht, The Netherlands
| | - Elfi E. H. G. Brouwers
- Department of Sexual Health, Infectious Diseases and Environmental Health, Living Lab Public Health, South Limburg Public Health Service, Heerlen, The Netherlands
- Department of Social Medicine, Care and Public Health Research Institute (CAPHRI), Maastricht University, Maastricht, The Netherlands
| | - Christian J. P. A. Hoebe
- Department of Sexual Health, Infectious Diseases and Environmental Health, Living Lab Public Health, South Limburg Public Health Service, Heerlen, The Netherlands
- Department of Social Medicine, Care and Public Health Research Institute (CAPHRI), Maastricht University, Maastricht, The Netherlands
- Department of Medical Microbiology, Infectious Diseases and Infection Prevention, Care and Public Health Research Institute (CAPHRI), Maastricht University Medical Center (MUMC+), Maastricht, The Netherlands
| | - Nicole H. T. M. Dukers-Muijrers
- Department of Sexual Health, Infectious Diseases and Environmental Health, Living Lab Public Health, South Limburg Public Health Service, Heerlen, The Netherlands
- Department of Health Promotion, Care and Public Health Research Institute (CAPHRI), Maastricht University, Maastricht, The Netherlands
| | - Jamila Bouchaara
- Department of Sexual Health, Infectious Diseases and Environmental Health, Living Lab Public Health, South Limburg Public Health Service, Heerlen, The Netherlands
| | - Inge H. M. van Loo
- Department of Medical Microbiology, Infectious Diseases and Infection Prevention, Care and Public Health Research Institute (CAPHRI), Maastricht University Medical Center (MUMC+), Maastricht, The Netherlands
| | - Casper D. J. den Heijer
- Department of Sexual Health, Infectious Diseases and Environmental Health, Living Lab Public Health, South Limburg Public Health Service, Heerlen, The Netherlands
- Department of Social Medicine, Care and Public Health Research Institute (CAPHRI), Maastricht University, Maastricht, The Netherlands
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Chien LN, Vargas-Zambrano JC, Ku MY. Decreasing hepatitis B seroprevalence in pregnant women in Taiwan between 2016 and 2021: a claim-based cohort study. BMC Public Health 2025; 25:111. [PMID: 39789546 PMCID: PMC11721186 DOI: 10.1186/s12889-025-21308-3] [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: 08/21/2024] [Accepted: 01/03/2025] [Indexed: 01/12/2025] Open
Abstract
BACKGROUND Hepatitis B virus (HBV) surface antigen (HBsAg) seroprevalence was high before the national vaccine policy was introduced in Taiwan, indicating significant HBV infection rates. The success of the HBV immunization program and other preventive measures likely led to decreased HBsAg prevalence among pregnant women. This study reports on the HBV seroprevalence among pregnant women in Taiwan from 2016 to 2021, including those potentially affected by the universal hepatitis B vaccination at birth. METHODS This claim-based cohort study included pregnant women with hospital-based prenatal HBV screening data: 162,662 for HBsAg and 161,729 for HBeAg, from 2016 to 2021. Patient medical records were reviewed to collect information on demographic characteristics and other health conditions. Logistic regression models were used to identify risk factors associated with HBsAg and HBV e antigen (HBeAg) positivity. RESULTS The seroprevalence for HBsAg and HBeAg during the study period was 4.0% and 0.6%, respectively. HBsAg positivity was highest among women born before July 1984 (pre-vaccination period; 8.6%), decreasing to 2.2% among those born between July 1986 and 1988 (national vaccination implementation) and further declining to 1.1% for those born after 1997. These data underscore the crucial role of large-scale immunization strategies in controlling HBV infections. Similarly, HBeAg positivity was highest among pregnant women born before the vaccination program (~ 1.0%), decreasing significantly to 0.4% for those born after 1989. The results showed geographic variations, potentially reflecting factors such as the mother's age and foreign nationality. However, the birth year was the most crucial factor associated with HBV marker positivity. CONCLUSIONS The implementation of national vaccination programs has demonstrated significant success in reducing HBV seroprevalence among pregnant women, which is particularly evident in the substantial decrease in HBsAg seroprevalence in Taiwan post-July 1986. These findings emphasize the importance of continued and consistent vaccination efforts, supporting the need for ongoing public health strategies to combat HBV infections effectively.
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Affiliation(s)
- Li-Nien Chien
- Institute of Health and Welfare Policy, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
| | | | - Meng-Yun Ku
- Graduate Institute of Data Science, College of Management, Taipei Medical University, Taipei, Taiwan
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Morita C, Wada M, Ohsaki E, Kimura-Ohba S, Ueda K. Generation of Replication-Competent Hepatitis B Virus Harboring Tagged Polymerase for Visualization and Quantification of the Infection. Microbiol Immunol 2025; 69:43-58. [PMID: 39620377 DOI: 10.1111/1348-0421.13183] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2024] [Revised: 11/03/2024] [Accepted: 11/04/2024] [Indexed: 01/07/2025]
Abstract
Hepatitis B virus (HBV) infection is a serious global health problem causing acute and chronic hepatitis and related diseases. Approximately, 296 million patients have been chronically infected with the virus, leading to cirrhosis and hepatocellular carcinoma. Although HBV polymerase (HBVpol, pol) plays a pivotal role in HBV replication and must be a definite therapeutic target. The problems are that the detailed functions and intracellular dynamics of HBVpol remain unclear. Here, we constructed two kinds of tagged HBVpol, PA-tagged and HiBiT-tagged pol, and the HBV-producing vectors. Each PA tag and HiBiT tag were inserted into N-terminus of spacer region on HBVpol open reading frame. Transfection of the plasmids into HepG2 cells led to production of HBV. These tagged HBVpol were detectable in HBV replicating cells and pol-HiBiT enabled quantitative analysis. Furthermore, these recombinant HBV were infectious to primary human hepatocytes. Thus, we successfully designed infectious and replication-competent recombinant HBV harboring detectable tagged HBVpol. Such infectious recombinant HBV will provide a novel tool to study HBVpol dynamics and develop new therapeutics against HBV.
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Grants
- This research was supported by Grants from the Japan Agency for Medical Research and Development (AMED) Grants (16fk0310504h0005, 17fk0310105h0001, 18fk0310105h0002, 19fk0310105h0003, 20fk0310105h0004, 21fk0310105h005, 22fk0310505h0001, 23fk0310505h0002, and 24fk0310505h003) to K.U. and from JST SPRING, Grant Number JPMJSP2138, to C.M. and from the Osaka University Transdisciplinary Program for Biomedical Entrepreneurship and Innovation (WISE program) to C.M.
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Affiliation(s)
- Chiharu Morita
- Division of Virology, Department of Microbiology and Immunology, Osaka University Graduate School of Medicine, Osaka, Japan
| | - Masami Wada
- Division of Virology, Department of Microbiology and Immunology, Osaka University Graduate School of Medicine, Osaka, Japan
| | - Eriko Ohsaki
- Division of Virology, Department of Microbiology and Immunology, Osaka University Graduate School of Medicine, Osaka, Japan
- Center for Infectious Disease Education and Research (CiDER), Osaka, Japan
| | - Shihoko Kimura-Ohba
- Division of Virology, Department of Microbiology and Immunology, Osaka University Graduate School of Medicine, Osaka, Japan
| | - Keiji Ueda
- Division of Virology, Department of Microbiology and Immunology, Osaka University Graduate School of Medicine, Osaka, Japan
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Yu H, Ren J, Deng H, Li L, Zhang Z, Cheng S, Guo Z, Huang A, Dang Y, Song K, Wu D, Yao X, Qin Y, Yang Z, Xu K, He X, Chen J. Neuropilin-1 is a novel host factor modulating the entry of hepatitis B virus. J Hepatol 2025; 82:37-50. [PMID: 38960374 DOI: 10.1016/j.jhep.2024.06.032] [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: 04/18/2024] [Revised: 05/30/2024] [Accepted: 06/24/2024] [Indexed: 07/05/2024]
Abstract
BACKGROUND & AIMS Sodium taurocholate cotransporting polypeptide (NTCP) has been identified as the cellular receptor for HBV. However, hepatocytes expressing NTCP exhibit varying susceptibilities to HBV infection. This study aimed to investigate whether other host factors modulate the process of HBV infection. METHODS Liver biopsy samples obtained from children with hepatitis B were used for single-cell sequencing and susceptibility analysis. Primary human hepatocytes, HepG2-NTCP cells, and human liver chimeric mice were used to analyze the effect of candidate host factors on HBV infection. RESULTS Single-cell sequencing and susceptibility analysis revealed a positive correlation between neuropilin-1 (NRP1) expression and HBV infection. In the HBV-infected cell model, NRP1 overexpression before HBV inoculation significantly enhanced viral attachment and internalization, and promoted viral infection in the presence of NTCP. Mechanistic studies indicated that NRP1 formed a complex with LHBs (large hepatitis B surface proteins) and NTCP. The NRP1 b domain mediated its interaction with conserved arginine residues at positions 88 and 92 in the preS1 domain of LHBs. This NRP1-preS1 interaction subsequently promoted the binding of preS1 to NTCP, facilitating viral infection. Moreover, disruption of the NRP1-preS1 interaction by the NRP1 antagonist EG00229 significantly attenuated the binding affinity between NTCP and preS1, thereby inhibiting HBV infection both in vitro and in vivo. CONCLUSIONS Our findings indicate that NRP1 is a novel host factor for HBV infection, which interacts with preS1 and NTCP to modulate HBV entry into hepatocytes. IMPACT AND IMPLICATIONS HBV infection is a global public health problem, but the understanding of the early infection process of HBV remains limited. Through single-cell sequencing, we identified a novel host factor, NRP1, which modulates HBV entry by interacting with HBV preS1 and NTCP. Moreover, antagonists targeting NRP1 can inhibit HBV infection both in vitro and in vivo. This study could further advance our comprehension of the early infection process of HBV.
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Affiliation(s)
- Haibo Yu
- Department of Infectious Diseases, Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
| | - Jihua Ren
- Department of Infectious Diseases, Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China; College of Biomedical Engineering, Chongqing Medical University, Chongqing, China
| | - Haijun Deng
- Department of Infectious Diseases, Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
| | - Linfeng Li
- Basic Medicine Research and Innovation Center for Novel Target and Therapeutic Intervention (Ministry of Education), Institute of Life Sciences, Chongqing Medical University, Chongqing, China
| | - Zhenzhen Zhang
- Chongqing Key Laboratory of Child Infection and Immunity, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders, Department of Infectious Diseases, The Children's Hospital of Chongqing Medical University, Chongqing, China
| | - Shengtao Cheng
- Department of Infectious Diseases, Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
| | - Zufeng Guo
- Basic Medicine Research and Innovation Center for Novel Target and Therapeutic Intervention (Ministry of Education), Institute of Life Sciences, Chongqing Medical University, Chongqing, China
| | - Ailong Huang
- Department of Infectious Diseases, Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
| | - Yongjun Dang
- Basic Medicine Research and Innovation Center for Novel Target and Therapeutic Intervention (Ministry of Education), Institute of Life Sciences, Chongqing Medical University, Chongqing, China
| | - Kunling Song
- Basic Medicine Research and Innovation Center for Novel Target and Therapeutic Intervention (Ministry of Education), Institute of Life Sciences, Chongqing Medical University, Chongqing, China
| | - Daiqing Wu
- Department of Infectious Diseases, Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
| | - Xinyan Yao
- Department of Infectious Diseases, Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
| | - Yiping Qin
- Department of Infectious Diseases, Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
| | - Zhen Yang
- Department of Infectious Diseases, Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
| | - Kexin Xu
- Department of Infectious Diseases, Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
| | - Xin He
- Department of Infectious Diseases, Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
| | - Juan Chen
- Department of Infectious Diseases, Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China; College of Biomedical Engineering, Chongqing Medical University, Chongqing, China.
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Zhong W, Wang C, Wang J, Chen T. Machine learning models to further identify advantaged populations that can achieve functional cure of chronic hepatitis B virus infection after receiving Peg-IFN alpha treatment. Int J Med Inform 2025; 193:105660. [PMID: 39454328 DOI: 10.1016/j.ijmedinf.2024.105660] [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: 04/26/2024] [Revised: 10/12/2024] [Accepted: 10/18/2024] [Indexed: 10/28/2024]
Abstract
OBJECTIVE Functional cure is currently the highest goal of hepatitis B virus(HBV) treatment.Pegylated interferon(Peg-IFN) alpha is an important drug for this purpose,but even in the hepatitis B e antigen(HBeAg)-negative population,there is still a portion of the population respond poorly to it.Therefore,it is important to explore the influencing factors affecting the response rate of Peg-IFN alpha and establish a prediction model to further identify advantaged populations. METHODS We retrospectively analyzed 382 patients.297 patients were in the training set and 85 patients from another hospital were in the test set.The intersect features were extracted from all variables using the recursive feature elimination(RFE) algorithm, Boruta algorithm, and least absolute shrinkage and selection operator(LASSO) regression algorithm in the training dataset.Then,we employed six machine learning(ML) algorithms-Logistic Regression(LR),Random Forest(RF),Support Vector Machines(SVM),K Nearest Neighbors(KNN),Light Gradient Boosting Machine(LightGBM) and Extreme Gradient Boosting(XGBoost)-to develop the model.Internal 10-fold cross-validation helped determine the best-performing model,which was then tested externally.Model performance was assessed using metrics such as area under the curve(AUC) and other metrics.SHapley Additive exPlanations(SHAP) plots were used to interpret variable significance. RESULTS 138/382(36.13 %) patients achieved functional cure.HBsAg at baseline,HBsAg decline at week12,non-alcoholic fatty liver disease(NAFLD) and age were identified as significant variables.RF performed the best,with AUC value of 0.988,and maintained good performance in test set.The SHapley Additive exPlanations(SHAP) plot highlighted HBsAg at baseline and HBsAg decline at week 12 are the top two predictors.The web-calculator was designed to predict functional cure more conveniently(https://www.xsmartanalysis.com/model/list/predict/model/html?mid = 17054&symbol = 317ad245Hx628ko3uW51). CONCLUSION We developed a prediction model,which can be used to not only accurately identifies advantageous populations with Peg-IFN alpha,but also determines whether to continue subsequent Peg-IFN alpha.
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Affiliation(s)
- Wenting Zhong
- Department of Infectious Disease, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China
| | - Che Wang
- Department of Radiology Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China
| | - Jia Wang
- Department of Infectious Disease, The Eight Hospital of Xi'an, Xi'an, Shaanxi, China
| | - Tianyan Chen
- Department of Infectious Disease, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.
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Dong J, Liu C, Zhang M, Yu H, Zhao D, Bai X, Zheng M, Liu Y, Ji J, Li R, Shen W, Cai J. Prediction Modelling for Gastroesophageal Variceal Bleeding in Patients With Chronic Hepatitis B Using Four-dimensional Flow MRI. J Clin Exp Hepatol 2025; 15:102403. [PMID: 39296664 PMCID: PMC11405793 DOI: 10.1016/j.jceh.2024.102403] [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: 08/28/2023] [Accepted: 08/07/2024] [Indexed: 09/21/2024] Open
Abstract
Background/Aims In this study, we aim to develop a model for predicting gastroesophageal varices (GEV) bleeding in patients with chronic hepatitis B (CHB) by utilizing hemodynamic parameters obtained through four-dimensional flow MRI (4D flow MRI). Methods This study conducted a prospective enrollment of CHB patients suspected of GEV from October 2021 to May 2022. The severity of varices and bleeding risk were evaluated using clinical findings and upper gastrointestinal endoscopy, and patients were classified into high-risk and non-high-risk groups. The study utilized serological examination, ultrasonographic examination, and 4D flow MRI. Relevant parameters were selected through univariate and multivariate analyses, and a prediction model was established using binary logistic regression analysis. The model was combined with the Baveno Ⅵ/Ⅶ and Expanded Baveno Ⅵ/Ⅶ criteria to evaluate diagnostic efficacy and the risk of avoiding endoscopic examination. Results A total of 40 CHB patients were enrolled and categorized into the high-risk group (n = 15) and the non-high-risk group (n = 25). The spleen diameter and regurgitant fraction (R%) were independent predictors of variceal bleeding and a predictive model was established. The combination of this prediction model and the Baveno Ⅵ/Ⅶ criteria achieved high diagnostic efficiency, enabling 45.00% (18/40) of patients to be exempted from the unnecessary endoscopic procedure and the high-risk misclassification rate (0%) was less than 5%. Conclusion The prediction model generated by 4D flow MRI has the potential to assess the likelihood of varices and can be supplemented by the Baveno VI/VII criteria to improve diagnostic accuracy in CHB patients.
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Affiliation(s)
- Jinghui Dong
- Department of Radiology, The Fifth Medical Center of Chinese PLA General Hospital, Beijing 100039, China
| | - Changchun Liu
- Department of Radiology, The Fifth Medical Center of Chinese PLA General Hospital, Beijing 100039, China
| | - Mengmeng Zhang
- Department of Radiology, The Fifth Medical Center of Chinese PLA General Hospital, Beijing 100039, China
| | - Hailong Yu
- Department of Radiology, The Fifth Medical Center of Chinese PLA General Hospital, Beijing 100039, China
| | - Di Zhao
- Senior Department of Hepatology, The Fifth Medical Center of Chinese PLA General Hospital, Beijing 100039, China
| | - Xu Bai
- Department of Radiology, The Fifth Medical Center of Chinese PLA General Hospital, Beijing 100039, China
| | - Meng Zheng
- Department of Radiology, The Fifth Medical Center of Chinese PLA General Hospital, Beijing 100039, China
| | - Yuan Liu
- Department of Radiology, The Fifth Medical Center of Chinese PLA General Hospital, Beijing 100039, China
| | - Jiachen Ji
- Department of Biomedical Engineering, Center for Biomedical Imaging Research, Tsinghua Univercity, Beijing 100084, China
| | - Rui Li
- Department of Biomedical Engineering, Center for Biomedical Imaging Research, Tsinghua Univercity, Beijing 100084, China
| | - Wen Shen
- Department of Radiology, Tianjin First Center Hospital, Tianjin 300192, China
| | - Jianming Cai
- Department of Radiology, The Fifth Medical Center of Chinese PLA General Hospital, Beijing 100039, China
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Chu YD, Hsu CW, Ho PH, Chiou CY, Lin CL, Liang KH, Lai MW, Yeh CT. Evolution of hepatitis B virus polymerase and surface genes in patients receiving finite antiviral therapy. J Gastroenterol Hepatol 2025; 40:265-273. [PMID: 39500510 DOI: 10.1111/jgh.16791] [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: 07/23/2024] [Revised: 10/15/2024] [Accepted: 10/20/2024] [Indexed: 01/02/2025]
Abstract
BACKGROUND AND AIM Hepatitis B virus (HBV) reactivation could develop after withdrawal following a finite course of nucleoside analog (NA) therapy, leading to virological and clinical relapses. The genetic heterogeneity in the HBV surface and polymerase genes during finite NA therapy has not been carefully studied. METHODS Seven chronic HBV-infected patients experiencing relapses following entecavir (ETV; n = 5; Patients 1 to 5) or tenofovir disoproxil fumarate (TDF; n = 2; Patients 6 and 7) withdrawal were included. Sera obtained before treatment and at relapses were retrieved and submitted for DNA extraction and amplicon-specific deep sequencing. RESULTS ETV-treated patients had a longer time-to-relapse than that of TDF-treated patients (P = 0.0357). No drug-resistance related polymerase mutation was detected during relapses, except for a low percentage (1.4%) of rtM204I mutation in Patient 1. Two surface truncation mutations (sW216*; 40.9% and sW182*; 4.7%) detected before treatment in two TDF-treated patients (Patients 6 and 7, respectively) were overtaken by the wild types during subsequent drug-withdrawal-related relapses. The simultaneous presence of sG44E (T-cell epitope) and sE164G (B-cell epitope) mutations was associated with failure of HBV e antigen (HBeAg) seroclearance in ETV-treated patients. CONCLUSIONS In conclusion, HBV genome continues to evolve during the courses of finite antiviral therapies. Pre-existing surface truncation mutations can be overtaken by the wild types after relapses. The sG44E/sE164G mutations are associated with failure of HBeAg seroclearance.
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Affiliation(s)
- Yu-De Chu
- Liver Research Center, Chang Gung Memorial Hospital Linkou Branch, Taoyuan, Taiwan
| | - Chao-Wei Hsu
- Liver Research Center, Chang Gung Memorial Hospital Linkou Branch, Taoyuan, Taiwan
- Department of Hepatology and Gastroenterology, Chang Gung Memorial Hospital Linkou Branch, Taoyuan, Taiwan
| | - Pei-Huan Ho
- Liver Research Center, Chang Gung Memorial Hospital Linkou Branch, Taoyuan, Taiwan
- Department of Hepatology and Gastroenterology, Chang Gung Memorial Hospital Linkou Branch, Taoyuan, Taiwan
| | - Chih-Yung Chiou
- Liver Research Center, Chang Gung Memorial Hospital Linkou Branch, Taoyuan, Taiwan
| | - Chih-Lang Lin
- Liver Research Center, Chang Gung Memorial Hospital Linkou Branch, Taoyuan, Taiwan
- Liver Research Unit and Community Medicine Research Center, Keelung Chang Gung Memorial Hospital, Keelung, Taiwan
| | - Kung-Hao Liang
- Medical Research Department, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Ming-Wei Lai
- Liver Research Center, Chang Gung Memorial Hospital Linkou Branch, Taoyuan, Taiwan
- Department of Pediatrics, Division of Pediatric Gastroenterology, Liver Research Center, Chang Gung Memorial Hospital Linkou Branch, Taoyuan, Taiwan
| | - Chau-Ting Yeh
- Liver Research Center, Chang Gung Memorial Hospital Linkou Branch, Taoyuan, Taiwan
- Department of Hepatology and Gastroenterology, Chang Gung Memorial Hospital Linkou Branch, Taoyuan, Taiwan
- Institute of Stem Cell and Translational Cancer Research, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan
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An J, Jin N, Xie J, Ma Y, Liu H, Balajiang G, Liu S, Zhang X. Vaccination coverage of hepatitis B and associated factors among health care workers in Gansu province. Hum Vaccin Immunother 2024; 20:2383509. [PMID: 39132758 PMCID: PMC11321420 DOI: 10.1080/21645515.2024.2383509] [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: 04/23/2024] [Revised: 07/10/2024] [Accepted: 07/19/2024] [Indexed: 08/13/2024] Open
Abstract
The investigation was conducted to describe the status of coverage of HBV vaccination among the health care workers in Gansu province and to explore the associated factors of HBV vaccination in this study. A cross-sectional study was conducted among 1544 health care workers from 64 hospitals in Gansu province. A self-designed questionnaire was used to interview the health care workers about HBV vaccination coverage. A multivariate logistic regression model explored the associated factors with HBV vaccination. The vaccination coverage was 89.17% for health care workers, nurses (90.40%) had the highest rate, followed by administration staff (89.38%) and medical technicians (89.30%). The full-dose HBV vaccination coverage was 64.25% for health care workers, and administration staff (65.04%) had the highest rate, followed by nurses (65.00%). This study found that the associated factors with HBV vaccination and full-dose vaccination were the history of training and the detection of serological indicators. The coverage of HBV vaccination among health care workers in Gansu province was high, but full-dose HBV vaccination coverage was low. It is necessary to strengthen the HBV knowledge and training in HBV prevention and treatment among health care workers in Gansu Province.
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Affiliation(s)
- Jing An
- Immunization program department, Gansu Provincial Center for Disease Control and Prevention, Lanzhou, China
| | - Na Jin
- Immunization program department, Gansu Provincial Center for Disease Control and Prevention, Lanzhou, China
| | - Jingru Xie
- School of Public Health, Lanzhou University, Lanzhou, Gansu, China
| | - Yuxin Ma
- School of Public Health, Lanzhou University, Lanzhou, Gansu, China
| | - Haixia Liu
- School of Public Health, Lanzhou University, Lanzhou, Gansu, China
| | | | - Shuyu Liu
- Immunization program department, Gansu Provincial Center for Disease Control and Prevention, Lanzhou, China
| | - Xiaoshu Zhang
- Immunization program department, Gansu Provincial Center for Disease Control and Prevention, Lanzhou, China
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Wu M, Mai J, Zhang H, Zhang G, Mao J, Tang Y, Yan W, Wu W, Hou J, Liang X, Liu Z, Ding Y, Niu J. Safety, pharmacokinetics, and antiviral efficacy of the novel capsid assembly modulator GST-HG141 in patients with chronic hepatitis B: a phase 1 trial with a randomized, placebo-controlled design. Virol J 2024; 21:328. [PMID: 39707469 PMCID: PMC11662624 DOI: 10.1186/s12985-024-02584-8] [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: 09/10/2024] [Accepted: 11/21/2024] [Indexed: 12/23/2024] Open
Abstract
In preclinical studies, GST-HG141, a novel hepatitis B virus (HBV) capsid assembly modulator displayed potent anti-HBV activity in vitro and strong efficacy in HBV animal models. A randomized, double-blind, ascending phase 1b trial assessed the pharmacokinetics, safety, and efficacy of GST-HG141 in chronic hepatitis B (CHB) individuals. Thirty treatment-naïve CHB patients were enrolled in three cohorts (25, 50, and 100 mg twice orally after meals daily) over 28 days, with 10 subjects per cohort (8:2 ratio for GST-HG141 and placebo). Dose-related safety and tolerability, pharmacokinetic profiles, and drug responses were evaluated. GST-HG141 exhibited a generally favorable safety profile across all doses with predominantly mild adverse reactions, including three cases of grade 1 transaminase elevations. Significant reductions in HBV DNA and pregenomic RNA (pgRNA) levels were observed across all doses of (25, 50, and 100 mg of GST-HG141, twice-daily) after 28 days of treatment. Pharmacokinetic analysis showed a consistent linear trend in GST-HG141 concentrations, with mean trough concentrations ranging from 75 to 240 ng/mL. These concentrations adequately covered the protein binding-adjusted EC50 (16.89 ng/mL) by factors of 4.4, 11.1, and 14.6 for doses of 25, 50, and 100 mg, respectively. Our study demonstrated GST-HG141's well-tolerated profile up to 100 mg over 4 weeks, alongside robust antiviral activity in CHB patients, supporting its progression into further clinical investigation for CHB management.
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Affiliation(s)
- Min Wu
- Phase I Clinical Trial Unit, First Hospital, Jilin University, Jilin, China
| | - Jiajia Mai
- Phase I Clinical Trial Unit, First Hospital, Jilin University, Jilin, China
| | - Hong Zhang
- Phase I Clinical Trial Unit, First Hospital, Jilin University, Jilin, China
| | - George Zhang
- Fujian Akeylink Biotechnology Co., Ltd., Shanghai, China
| | - John Mao
- Fujian Akeylink Biotechnology Co., Ltd., Shanghai, China
| | - Yanan Tang
- Fujian Akeylink Biotechnology Co., Ltd., Shanghai, China
| | - Wenhao Yan
- Fujian Akeylink Biotechnology Co., Ltd., Shanghai, China
| | - Wenqiang Wu
- Fujian Akeylink Biotechnology Co., Ltd., Shanghai, China
| | - Jinlin Hou
- Department of Infectious Diseases and Hepatology Unit, Department of Infectious Diseases and Hepatology Unit, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Xieer Liang
- Department of Infectious Diseases and Hepatology Unit, Department of Infectious Diseases and Hepatology Unit, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Zhihong Liu
- Department of Infectious Diseases and Hepatology Unit, Department of Infectious Diseases and Hepatology Unit, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Yanhua Ding
- Phase I Clinical Trial Unit, First Hospital, Jilin University, Jilin, China.
- Phase I Clinical Research Center, The First Hospital of Jilin University, Changchun, Jilin, China.
| | - Junqi Niu
- Department of Hepatology, Center of Infectious Disease and Pathogen Biology, The First Hospital of Jilin University, Changchun, China.
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Akabuike OM, Aworh MK, Uzoebo NL, Erwat J, Agukwe O, Ngong K, Dangana A, Enwerem K, Abdullahi IN. Evaluating hepatitis B screening, prevalence, vaccination coverage, and linkage to care in Abuja, Nigeria: insights from a cross-sectional study. BMC Public Health 2024; 24:3475. [PMID: 39696217 DOI: 10.1186/s12889-024-21017-3] [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: 09/12/2024] [Accepted: 12/08/2024] [Indexed: 12/20/2024] Open
Abstract
BACKGROUND Hepatitis B virus (HBV) is a major global health threat, especially in Sub-Saharan Africa, where Nigeria has a prevalence exceeding 8%. Despite the availability of effective vaccines, inadequate coverage and lack of awareness have resulted in high rates of chronic infections and HBV-attributable liver disease. The study aimed to raise awareness of HBV, enroll participants for HBV screening, determine HBV prevalence across various communities, vaccinate negative cases and link positive cases to care. METHODS A cross-sectional study was conducted in 16 districts of Abuja from April 2022 to March 2023. Participants aged 18 and over were screened for hepatitis B, and those testing negative were offered on-site vaccination. Blood samples were collected and tested using HBV immunochromatographic tests and real-time polymerase chain reaction (RT-PCR) for HBV DNA quantification. Data were collected through interviews and analyzed using R software, with descriptive statistics calculated for continuous and categorical variables. Associations between socio-demographic factors and hepatitis B/vaccine status were assessed using the Chi-square test of independence. RESULTS Out of 3,245 individuals screened, 141 (4.3%) tested positive for HBV. The highest prevalence was observed in the 20-39 age group (5.9%), with males showing a higher infection rate (5.4%) compared to females (3.7%) [p = 0.02]. The mean age of HBV-positive individuals was significantly lower (30.8 years) than those negative for HBV (36.2 years) [p = < 0.001]. Among 2,506 participants who consented to vaccination, 2,488 received the first dose (99.3%), 1,834 the second dose (73.2%), and 1,100 the third dose (43.9%). Vaccination uptake declined with each subsequent dose, but more older participants completed the third dose. A similar pattern of HBV prevalence was observed across gender and age groups. CONCLUSION The study reveals a 4.3% prevalence of hepatitis B, with the highest infection rate among individuals aged 20-39 years, and males showing a higher prevalence than females. Although vaccination uptake was high for the first dose, adherence declined for subsequent doses. These findings highlight the need for targeted public health interventions, particularly among younger adults and males, to improve awareness and vaccination completion. Enhanced community engagement and sustained vaccination efforts are crucial for reducing HBV transmission and achieving better coverage.
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Affiliation(s)
| | - Mabel Kamweli Aworh
- Nigeria Field Epidemiology and Laboratory Training Programme, Asokoro, Abuja, Nigeria.
| | | | - John Erwat
- Remedium Plus Foundation, Efab Estate, Lokogoma, Abuja, Nigeria
| | | | - Kingsley Ngong
- Remedium Plus Foundation, Efab Estate, Lokogoma, Abuja, Nigeria
| | - Amos Dangana
- Remedium Plus Foundation, Efab Estate, Lokogoma, Abuja, Nigeria
| | - Kenneth Enwerem
- International Research Center of Excellence, Institute of Human Virology Nigeria (IHVN), Abuja, Nigeria
| | - Idris Nasir Abdullahi
- Department of Medical Laboratory Science, Faculty of Allied Health Sciences, College of Medical Sciences, Ahmadu Bello University, Zaria, Nigeria
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Heisig J, Nurmatov ZS, Riese P, Trittel S, Sattarova GJ, Temirbekova SN, Zhumagulova GZ, Nuridinova ZN, Derkenbaeva AA, Arykbaeva BK, Dzhangaziev BI, Prokein J, Klopp N, Illig T, Guzmán CA, Kasymov OT, Akmatov MK, Pessler F. Vaccination Schedule and Age Influence Impaired Responsiveness to Hepatitis B Vaccination: A Randomized Trial in Central Asia. Pathogens 2024; 13:1082. [PMID: 39770341 PMCID: PMC11728755 DOI: 10.3390/pathogens13121082] [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: 11/13/2024] [Revised: 12/03/2024] [Accepted: 12/05/2024] [Indexed: 01/16/2025] Open
Abstract
Vaccination against hepatitis B virus (HBV) is the most cost-efficient measure to prevent infection. Still, vaccination coverage among adults in Central Asia, including Kyrgyzstan, remains suboptimal, and data about immune responses to HBV vaccination are lacking. HBV vaccination is given as three injections, whereby the second and third doses are given 1 and 6 months after the first (0-1-6 scheme). However, compliance with the third dose is low in Kyrgyzstan, presumably due to the long time interval between the second and third doses, suggesting that a shortened vaccination schedule could result in better adherence and increased seroconversion. Thus, we conducted a randomized trial of individuals aged 17-66 years comparing the 0-1-6 scheme against a shorter 0-1-3 scheme. Primary outcome measures were post-vaccination titers and the percentage of participants with protective post-vaccination titers (≥10 mIU/mL). Compliance with the completeness of blood draws and administered third vaccine dose was better with the 0-1-3 scheme than with the 0-1-6 scheme. In both study arms combined, younger age (<40 years) was associated with better vaccine protection. The 0-1-6 scheme resulted in higher post-vaccination titers (52 versus 15 mIU/mL, p = 0.002) and a higher seroprotection rate (85% versus 64%, p = 0.01) than the 0-1-3 scheme, whereby post-vaccination titers correlated negatively with age in the 0-1-3 scheme. Thus, the 0-1-6 scheme should continue to be the preferred HBV vaccination schedule, but interventions to improve compliance with the third vaccine dose are needed.
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Affiliation(s)
- Janyn Heisig
- Department Vaccinology and Applied Microbiology, Helmholtz Centre for Infection Research, 38124 Braunschweig, Germany; (J.H.); (P.R.); (S.T.); (C.A.G.)
| | - Zuridin Sh. Nurmatov
- National Institute of Public Health, Ministry of Health of the Kyrgyz Republic, Bishkek 720005, Kyrgyzstan; (Z.S.N.); (G.J.S.); (S.N.T.); (Z.N.N.); (A.A.D.)
| | - Peggy Riese
- Department Vaccinology and Applied Microbiology, Helmholtz Centre for Infection Research, 38124 Braunschweig, Germany; (J.H.); (P.R.); (S.T.); (C.A.G.)
| | - Stephanie Trittel
- Department Vaccinology and Applied Microbiology, Helmholtz Centre for Infection Research, 38124 Braunschweig, Germany; (J.H.); (P.R.); (S.T.); (C.A.G.)
| | - Gulsunai J. Sattarova
- National Institute of Public Health, Ministry of Health of the Kyrgyz Republic, Bishkek 720005, Kyrgyzstan; (Z.S.N.); (G.J.S.); (S.N.T.); (Z.N.N.); (A.A.D.)
| | - Saikal N. Temirbekova
- National Institute of Public Health, Ministry of Health of the Kyrgyz Republic, Bishkek 720005, Kyrgyzstan; (Z.S.N.); (G.J.S.); (S.N.T.); (Z.N.N.); (A.A.D.)
| | - Gulnara Zh. Zhumagulova
- Republican Center for Immunoprophylaxis, Ministry of Health of the Kyrgyz Republic, Bishkek 720040, Kyrgyzstan;
| | - Zhanylai N. Nuridinova
- National Institute of Public Health, Ministry of Health of the Kyrgyz Republic, Bishkek 720005, Kyrgyzstan; (Z.S.N.); (G.J.S.); (S.N.T.); (Z.N.N.); (A.A.D.)
| | - Aisuluu A. Derkenbaeva
- National Institute of Public Health, Ministry of Health of the Kyrgyz Republic, Bishkek 720005, Kyrgyzstan; (Z.S.N.); (G.J.S.); (S.N.T.); (Z.N.N.); (A.A.D.)
| | - Bubuzhan K. Arykbaeva
- Ministry of Health of the Kyrgyz Republic, Bishkek 720040, Kyrgyzstan; (B.K.A.); (B.I.D.)
| | - Bakyt I. Dzhangaziev
- Ministry of Health of the Kyrgyz Republic, Bishkek 720040, Kyrgyzstan; (B.K.A.); (B.I.D.)
| | - Jana Prokein
- Hannover Unified Biobank, Hannover Medical School, 30625 Hannover, Germany; (J.P.); (N.K.); (T.I.)
| | - Norman Klopp
- Hannover Unified Biobank, Hannover Medical School, 30625 Hannover, Germany; (J.P.); (N.K.); (T.I.)
| | - Thomas Illig
- Hannover Unified Biobank, Hannover Medical School, 30625 Hannover, Germany; (J.P.); (N.K.); (T.I.)
| | - Carlos A. Guzmán
- Department Vaccinology and Applied Microbiology, Helmholtz Centre for Infection Research, 38124 Braunschweig, Germany; (J.H.); (P.R.); (S.T.); (C.A.G.)
| | - Omor T. Kasymov
- Scientific and Production Centre for Preventive Medicine, Ministry of Health of the Kyrgyz Republic, Bishkek 720005, Kyrgyzstan;
| | - Manas K. Akmatov
- Research Group Biomarkers for Infectious Diseases, TWINCORE Centre for Experimental and Clinical Infection Research, 30625 Hannover, Germany;
| | - Frank Pessler
- Research Group Biomarkers for Infectious Diseases, TWINCORE Centre for Experimental and Clinical Infection Research, 30625 Hannover, Germany;
- Centre for Individualised Infection Medicine, 30625 Hannover, Germany
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Chen JS, Levintow SN, Tran HV, Sibley AL, Blackburn NA, Sripaipan T, Hutton HE, Go VF, Chander G. Prevalence of hepatitis coinfection and substance use among antiretroviral therapy clinic clients with hazardous alcohol use in Vietnam. PLOS GLOBAL PUBLIC HEALTH 2024; 4:e0003744. [PMID: 39636896 PMCID: PMC11620398 DOI: 10.1371/journal.pgph.0003744] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/17/2024] [Accepted: 09/29/2024] [Indexed: 12/07/2024]
Abstract
The confluence of injection drug use (IDU), alcohol consumption, and viral hepatitis increases morbidity among persons living with HIV (PWH). We present a secondary analysis of a randomized controlled trial of alcohol reduction interventions in Thai Nguyen, Vietnam conducted between 2016-2018. We assessed hepatitis B (HBV) and hepatitis C (HCV) coinfection among PWH reporting hazardous alcohol consumption and examined differences in IDU and alcohol use by coinfection status. Participants were ≥18 years old, living with HIV, and reported hazardous alcohol consumption per the WHO Alcohol Use Disorders Identification Test Consumption (AUDIT-C; score ≥4 for men, score ≥3 for women). At enrollment, participants were tested for hepatitis coinfection with HBV surface antigen tests and rapid serological HCV tests. Demographic information, IDU, and recent alcohol consumption were assessed via behavioral survey and 30-day timeline follow back. Fishers Exact and Kruskal-Wallis tests were used for statistical testing. Hepatitis coinfection was common among the 440 enrolled PWH: HCV: n = 355 (81%); HBV: n = 5 (1%); HBV and HCV: n = 37 (8%). Only 10% (n = 43) of participants had no hepatitis coinfection. Among those who tested positive for HBV, 36% had previously been diagnosed with HBV; among those who tested seropositive for HCV, 18% had previously received an HCV diagnosis. History of IDU was higher among those with hepatitis coinfection (HBV or HCV coinfection: 88%; HBV and HCV coinfections: 97%) than those without hepatitis coinfection (7%; p<0.01). Median days of alcohol consumption in the last 30 days was higher among those with coinfection (HBV or HCV coinfection: 20 (Interquartile Range (IQR): 10-30); HBV and HCV coinfections: 22 (IQR: 13-28) than those without hepatitis coinfection (10; IQR: 6-21; p<0.01). The syndemic conditions of HIV, hepatitis, IDU, and alcohol use are deeply entangled and challenging to parse out. Integrated health services are warranted to reduce the risk of liver-related morbidity.
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Affiliation(s)
- Jane S. Chen
- Department of Health Behavior, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America
| | - Sara N. Levintow
- Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America
| | - Ha V. Tran
- Department of Health Behavior, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America
| | - Adams L. Sibley
- Department of Health Behavior, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America
| | - Natalie A. Blackburn
- RTI International, Research Triangle Park, North Carolina, United States of America
| | - Teerada Sripaipan
- Department of Health Behavior, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America
| | - Heidi E. Hutton
- Department of Psychiatry and Behavioral Sciences, School of Medicine, Johns Hopkins University, Baltimore, Maryland, United States of America
| | - Vivian F. Go
- Department of Health Behavior, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America
| | - Geetanjali Chander
- Division of General Internal Medicine, University of Washington, Seattle, Washington, United States of America
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Ivanga M, Parkin DM, Filankembo Kava A, Nziengui Tirogo C, Nzamba Bissielou P, Kabena A, Engohan Aloghe C, Revignet R, Parente A, Blanquet V, Ngoungou EB, Koumakpayi IH, Belembaogo E. Cancer in the Grand Libreville, Gabon (2013-2017). Cancer Epidemiol 2024; 93:102695. [PMID: 39527871 DOI: 10.1016/j.canep.2024.102695] [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: 04/12/2024] [Revised: 10/10/2024] [Accepted: 10/25/2024] [Indexed: 11/16/2024]
Abstract
BACKGROUND The burden of cancer is expected to nearly double in sub-Saharan Africa over the next 20 years. In Gabon, the primary population-based cancer registry to be established is located in the Grand Libreville. This study presents cancer incidence rates covering the first 5-year period of registration in this region. PATIENTS AND METHODS 1,549 cancer cases were recorded among residents of the Grand Libreville between 2013 and 2017, 955 (61.6 %) women and 594 (38.3 %) males. RESULTS The age standardized incidence rates (ASR) for all sites were 73.3 per 105 in females and 47.7 per 105 in males, rather similar from those observed in neighbouring countries of central Africa. Breast (ASR 19.0 per 105) and cervical cancers (ASR 16.3 per 105) accounted for half of female cancers. Prostate (ASR 12.0 per 105), liver (ASR 5.1 per 105) and colorectal cancers (ASR of 5.0 per 105) accounted for 41.1 % of male cancers. CONCLUSION Breast and prostate cancers ranked first in females and males, respectively, even if the incidences appear much lower in comparison with other regional cancer registries rates, implying they may be underestimated. Cancers of the digestive organs were markedly more frequent in men than women, especially for liver, colorectal (and anus) and the mouth and pharynx. The incidence rates of these latter cancers are relatively similar to those of other registries of the central African region. These results may be of importance for implementing more adapted strategies in the battle against cancer.
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Affiliation(s)
- Mahine Ivanga
- Institut de Cancérologie d'Akanda, Akanda, BP 23902 Gabon.
| | - D Maxwell Parkin
- Nutffield Department of Population Health, University of Oxford, Oxford OX3 7LF United Kingdom
| | | | | | | | - Alex Kabena
- Institut de Cancérologie d'Akanda, Akanda, BP 23902 Gabon
| | | | - Rose Revignet
- Institut de Cancérologie d'Akanda, Akanda, BP 23902 Gabon
| | - Alexis Parente
- INSERM U1094, INRAE USC1501, IRD U270, EpiMaCT, Epidémiologie des maladies chroniques en zone tropicale, Univ, Limoges, 2 Rue Pr Descottes, Limoges 87000, France
| | - Veronique Blanquet
- INSERM U1094, INRAE USC1501, IRD U270, EpiMaCT, Epidémiologie des maladies chroniques en zone tropicale, Univ, Limoges, 2 Rue Pr Descottes, Limoges 87000, France
| | - Edgard Brice Ngoungou
- INSERM U1094, INRAE USC1501, IRD U270, EpiMaCT, Epidémiologie des maladies chroniques en zone tropicale, Univ, Limoges, 2 Rue Pr Descottes, Limoges 87000, France; Unité de Recherche en Epidémiologie des maladies (UREMCSE), Univ. Des Sciences de la Santé, Owendo, Gabon
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Madihi S, Charoute H, Boukaira S, Bouafi H, Baha W, Zyad A, Benani A. Virological characterization of Hepatitis B virus infection in Morocco: A ten-years study (2014 - 2023). Diagn Microbiol Infect Dis 2024; 110:116502. [PMID: 39191154 DOI: 10.1016/j.diagmicrobio.2024.116502] [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: 07/15/2024] [Revised: 08/16/2024] [Accepted: 08/20/2024] [Indexed: 08/29/2024]
Abstract
In alignment with Morocco's national strategy for eliminating viral hepatitis, we aimed to characterize and update the virological profile of chronic hepatitis B patients. Demographic, serological and molecular parameters of 804 HBsAg-positive patients were retrospectively analyzed. Overall, 58.24 % were HBV-positive (55.37 % males, p = 0.74). The median age was 46 years (37-57). Patients ≤ 24 years comprised 5 % of HBsAg-positive and 4.34 % of HBV-positive cases. The median viral load was 2.62 log10 IU/mL (1.87-3.44). The prevalent genotypes were D (91.04 %), A (7.55 %) and E (1.41 %). Liver enzymes were normal in most of cases. 91.04 % of patients were HBeAg-negative, with 92.23 % having genotype D (p < 0.001). Co-infection rates with other hepatitis viruses were low. Significant associations were found between HBeAg-negative status, genotype D, viral load, and liver enzyme levels (p < 0.001). We highlighted the need for prenatal HBsAg screening for pregnant women and prioritizing the birth-dose vaccine to prevent mother-to-child transmission, especially after the COVID-19 pandemic.
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Affiliation(s)
- Salma Madihi
- Molecular Biology Laboratory, Institut Pasteur du Maroc, Casablanca, Morocco; Team of Experimental Oncology and Natural Substances, Cellular and Molecular Immuno pharmacology, Sultan Moulay Slimane University, Faculty of Sciences and Technologies, Beni Mellal, Morocco.
| | - Hicham Charoute
- Research Unit of Epidemiology, Biostatistics and Bioinformatics, Institut Pasteur du Maroc, Casablanca, Morocco
| | - Samia Boukaira
- Molecular Biology Laboratory, Institut Pasteur du Maroc, Casablanca, Morocco; Molecular Microbiology and Biology Laboratory, Faculty of Sciences, Mohammed V University, Rabat, Morocco
| | - Hind Bouafi
- Human Genomics and Genetics Laboratory, Pasteur Institute of Morocco, Casablanca, Morocco
| | - Warda Baha
- Molecular Biology Laboratory, Institut Pasteur du Maroc, Casablanca, Morocco
| | - Abdelmajid Zyad
- Team of Experimental Oncology and Natural Substances, Cellular and Molecular Immuno pharmacology, Sultan Moulay Slimane University, Faculty of Sciences and Technologies, Beni Mellal, Morocco
| | - Abdelouaheb Benani
- Molecular Biology Laboratory, Institut Pasteur du Maroc, Casablanca, Morocco
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50
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Ou Yang WY, Tsai YS, Liu YH, Wang YF, Hsiao CT, Lai KL, Lee YC, Liao YC. Preceding hepatitis B virus infection is highly prevalent in patients with neuromyelitis optica spectrum disorder in Taiwan. Mult Scler Relat Disord 2024; 92:105923. [PMID: 39418777 DOI: 10.1016/j.msard.2024.105923] [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: 05/18/2024] [Revised: 10/01/2024] [Accepted: 10/06/2024] [Indexed: 10/19/2024]
Abstract
BACKGROUND Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune inflammatory disease of the central nervous system, characterized by pathogenic anti-Aquaporin-4 antibodies (AQP4-Ab). Given that infections can trigger autoimmune responses, we investigated the association between Hepatitis B virus (HBV) infection and NMOSD. METHODS HBV and hepatitis C virus serologies were analyzed in 105 NMOSD patients, 85 multiple sclerosis (MS) patients, and 1,661 healthy Taiwanese controls. Participants were classified into four HBV infection statuses (acute, chronic, resolved, and never infected), and further grouped by vaccination status. Logistic regression was used to estimate odds ratios (OR) for NMOSD development in individuals with chronic or resolved HBV infection. RESULTS Among those born before the Taiwan's universal vaccination program, 63.4 % of NMOSD patients had resolved HBV infection, compared to 30.6 % of MS patients and 16.4 % of controls. Resolved HBV infection was associated with a 2.3-fold increased risk for NMOSD development (95 % CI, 1.4-3.8), but not with MS risk. In the post-vaccination cohort, resolved HBV infection remained more frequent in NMOSD patients (8.7 %) than in MS (0 %) and controls (1.8 %). NMOSD patients with resolved HBV infection had later disease onset by 14.6 years and higher Expanded Disability Status Scale (EDSS) scores compared to those without HBV infection, even after adjusting for age and sex (3.5 ± 1.9 vs. 2.2 ± 1.8, p < 0.001). CONCLUSION Preceding HBV infection is prevalent among Taiwanese NMOSD patients and is associated with increased disease risk, older age at onset, and greater disability. Screening for HBV is essential for NMOSD patients, particularly in endemic regions.
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Affiliation(s)
- Wen-Yu Ou Yang
- Department of Neurology, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Yu-Shuen Tsai
- Cancer and Immunology Research Center, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Yi-Hong Liu
- Department of Neurology, Taoyuan General Hospital, Ministry of Health and Welfare, Taoyuan, Taiwan
| | - Yen-Feng Wang
- Department of Neurology, Taipei Veterans General Hospital, Taipei, Taiwan; Faculty of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Cheng-Tsung Hsiao
- Department of Neurology, Taipei Veterans General Hospital, Taipei, Taiwan; Faculty of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Kuan-Lin Lai
- Department of Neurology, Taipei Veterans General Hospital, Taipei, Taiwan; Faculty of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Yi-Chung Lee
- Department of Neurology, Taipei Veterans General Hospital, Taipei, Taiwan; Faculty of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan; Brain Research Center, National Yang Ming Chiao Tung University, Taipei, Taiwan; Center for Intelligent Drug Systems and Smart Bio-devices, National Yang Ming Chiao Tung University, Taipei, Taiwan.
| | - Yi-Chu Liao
- Department of Neurology, Taipei Veterans General Hospital, Taipei, Taiwan; Faculty of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan; Brain Research Center, National Yang Ming Chiao Tung University, Taipei, Taiwan.
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