1
|
Wang C, Zai W, Zhao K, Li Y, Shi B, Wu M, Zhou X, Kozlowski M, Zhang X, Fang Z, Yuan Z. Potential role of liver-resident CD3 + macrophages in HBV clearance in a mouse hepatitis B model. JHEP Rep 2025; 7:101323. [PMID: 40143948 PMCID: PMC11937660 DOI: 10.1016/j.jhepr.2024.101323] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/20/2024] [Revised: 12/18/2024] [Accepted: 12/23/2024] [Indexed: 03/28/2025] Open
Abstract
Background & Aims Chronic HBV infection usually causes cirrhosis and hepatocellular carcinoma. Comparative investigations of acute and chronic HBV cases would help determine the immune responses crucial for viral clearance. Methods A fast-cleared HBV mouse model was established in Alb-Cre mice via hydrodynamic injection of HBV plasmid, while persistent HBV model mice were generated via recombinant covalently closed circular DNA-adeno-associated virus 8 infection. The single-cell transcriptomes of CD45+ intrahepatic non-parenchymal cells from these mice were conducted. Multiplexed immunohistochemistry and flow cytometry were used to confirm the findings from single-cell transcriptomes. Transwell, coculture, and adoptive transfer experiments were performed to study the generation and functions of macrophages. Results Twenty-four clusters of immune cells were identified. Myeloid cells, including granulocytes, monocytes, and dendritic cells, are activated early in HBV fast-cleared mice. Significantly, a cluster of CD3+ macrophages was found in the viral clearance phase, which was confirmed in liver tissue from five acute patients with HBV. These cells highly expressed CXCL1, tumor necrosis factor alpha, and HBsAg-specific T cell receptors. The transwell assay revealed that CD3+ macrophages originate from macrophages (n = 6). T cells and anti-HBsAg antibodies are indispensable for their differentiation, which was further confirmed in T- and/or B-cell-deficient mice. Interestingly, these CD3+ macrophages capable of killing peptide-loaded hepatocytes and engulfing IgG-coated beads were persistently detectable in the mouse liver for 10 weeks after HBV clearance. The expression levels of CD5L and Bcl2, two classical antiapoptotic proteins, increased (p <0.001), suggesting that the CD3+ macrophages are long-term resident populations. Finally, adoptive transfer of CD3+ macrophages accelerated HBV clearance in mice (n = 5, p <0.01). Conclusions We identified long-term polyfunctional CD3+ macrophages residing in HBV fast-cleared livers that could help elucidate the immune responses involved in eliminating HBV. Impact and implications The liver is a special organ with unique immune characteristics and tolerance to foodborne antigens. Chronic infections can develop in newborns after exposure to HBV; however, acute infections usually occur in adults, indicating that immune cells in the liver tissue microenvironment can also effectively fight against the virus. Nevertheless, the mechanisms involved in acute HBV infection have rarely been studied. In this study, we identified a macrophage population with both T cell and macrophage characteristics in the livers of acute HBV model mice and revealed that these macrophages play important roles in HBV clearance. Moreover, we confirmed that this population is derived from macrophages in the presence of virus-specific T cells and antibodies. This finding highlights the complexity of antiviral immune responses in liver microenvironments.
Collapse
Affiliation(s)
- Cong Wang
- Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Research Unit of Cure of Chronic Hepatitis B Virus Infection (CAMS), Shanghai Frontiers Science Center of Pathogenic Microbes and Infection, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai, China
- Shanghai Public Health Clinical Center, Shanghai Medical College of Fudan University, Shanghai, China
| | - Wenjing Zai
- Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Research Unit of Cure of Chronic Hepatitis B Virus Infection (CAMS), Shanghai Frontiers Science Center of Pathogenic Microbes and Infection, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai, China
| | - Kuangjie Zhao
- Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Research Unit of Cure of Chronic Hepatitis B Virus Infection (CAMS), Shanghai Frontiers Science Center of Pathogenic Microbes and Infection, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai, China
| | - Yaming Li
- Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Research Unit of Cure of Chronic Hepatitis B Virus Infection (CAMS), Shanghai Frontiers Science Center of Pathogenic Microbes and Infection, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai, China
| | - Bisheng Shi
- Shanghai Public Health Clinical Center, Shanghai Medical College of Fudan University, Shanghai, China
| | - Min Wu
- Shanghai Public Health Clinical Center, Shanghai Medical College of Fudan University, Shanghai, China
| | - Xiaohui Zhou
- Shanghai Public Health Clinical Center, Shanghai Medical College of Fudan University, Shanghai, China
| | - Maya Kozlowski
- Shanghai Public Health Clinical Center, Shanghai Medical College of Fudan University, Shanghai, China
| | - Xiaonan Zhang
- Shanghai Public Health Clinical Center, Shanghai Medical College of Fudan University, Shanghai, China
| | - Zhong Fang
- Liver Cancer Institute of Zhongshan Hospital and Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Fudan University, Shanghai, China
| | - Zhenghong Yuan
- Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Research Unit of Cure of Chronic Hepatitis B Virus Infection (CAMS), Shanghai Frontiers Science Center of Pathogenic Microbes and Infection, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai, China
| |
Collapse
|
2
|
Khetsuriani N, Tursunova D, Kasimova R, Sharapov S, Stewart B, Matyakubov M, Latipov R, Mosina L, Yusupaliyev B, Musabaev E. Prevalence of chronic hepatitis B virus infection among children in Uzbekistan: Impact of vaccination. Vaccine 2025; 48:126743. [PMID: 39862544 DOI: 10.1016/j.vaccine.2025.126743] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2024] [Revised: 12/08/2024] [Accepted: 01/12/2025] [Indexed: 01/27/2025]
Abstract
BACKGROUND Uzbekistan, a highly endemic country for hepatitis B virus (HBV), introduced infant vaccination with hepatitis B vaccine (HepB) in 2001. Since 2002, it had ≥90 % reported immunization coverage for ≥3 doses of HepB (HepB3) and the birth dose (HepB-BD). However, the impact of HepB vaccination and the progress towards achieving the regional hepatitis B control and global viral hepatitis B elimination goals had not been assessed. METHODS To determine current HBsAg prevalence among children in Uzbekistan, in 2022, we conducted a nationwide serosurvey among schoolchildren (grades 1-3) using a stratified, multi-stage cluster design. Participants' basic demographics and HepB immunization information were obtained. Blood specimens were tested for HBsAg using a WHO-prequalified rapid test (Bioline HBsAg WB, Abbott Diagnostics). Samples with positive and indeterminate results were tested for HBsAg by ELISA (Murex HBsAg Version3, Diasorine). Weighted proportions and adjusted 95 % confidence intervals (CI) were calculated. RESULTS Of 4119 children enrolled in 148 schools, blood was collected from 3753 (91.1 %) and immunization data were available for 3833 (93.3 %). National HBsAg prevalence was 0.20 % (adjusted 95 % CI, 0.09 %-0.38 %). Among children with available immunization data, 97.7 % (97.2 %-98.1 %) received ≥3 HepB doses and 94.9 % (94.1 %-95.5 %) received HepB-BD, including timely HepB-BD in 93.7 % (92.9 %-94.5 %). CONCLUSIONS The survey demonstrated that Uzbekistan has met the <0.5 % European regional HBsAg seroprevalence target and has made substantial progress towards meeting the <0.1 % HBsAg seroprevalence target for the elimination of HBV mother to-child transmission (MTCT). Based on these findings and ≥ 90 % HepB-BD and HepB3 coverage, in 2023, Uzbekistan was validated as having achieved the regional hepatitis B control goal. To achieve the elimination of MTCT of HBV, additional interventions, including improving antenatal screening for HBsAg, providing antiviral treatment of eligible HBsAg-positive pregnant women and hepatitis B immunoglobulin to infants born to HBsAg-positive mothers, should be considered.
Collapse
Affiliation(s)
| | - Dilorom Tursunova
- Service for Sanitary-Epidemiological Welfare and Public Health, Ministry of Health, Tashkent, Uzbekistan
| | - Rano Kasimova
- Institute of Virology, Tashkent, Uzbekistan; Central Asian University, Tashkent, Uzbekistan
| | | | - Brock Stewart
- Centers for Disease Control and Prevention, Atlanta, USA
| | - Mansurbek Matyakubov
- Institute of Virology, Tashkent, Uzbekistan; Republican Specialized Scientific and Practical Medical Center of Epidemiology, Microbiology, Infectious and Parasitic Diseases, Tashkent, Uzbekistan
| | - Renat Latipov
- World Health Organization Uzbekistan Country Office, Tashkent, Uzbekistan
| | - Liudmila Mosina
- World Health Organization Regional Office for Europe, Copenhagen, Denmark
| | - Bakhodir Yusupaliyev
- Service for Sanitary-Epidemiological Welfare and Public Health, Ministry of Health, Tashkent, Uzbekistan
| | | |
Collapse
|
3
|
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.
Collapse
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
| |
Collapse
|
4
|
Li Z, Cao J, Li K, Wu Y, Luo Z, Cao R, Cheng Z, Tian Z, Han Y, Lai Y, Wang B, Chen S. Causal associations between osteoporosis and HBV infection across Asian and European populations: evidence from Mendelian randomization and colocalization analysis. Front Endocrinol (Lausanne) 2025; 15:1419303. [PMID: 39911237 PMCID: PMC11794126 DOI: 10.3389/fendo.2024.1419303] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/18/2024] [Accepted: 12/19/2024] [Indexed: 02/07/2025] Open
Abstract
Introduction Clinical studies have demonstrated a potential association between chronic hepatitis caused by hepatitis B virus (HBV) infection and osteoporosis. However, the causal relationship between HBV infection and osteoporosis remains to be determined. Methods We investigated whether HBV infection is causally associated with osteoporosis using Mendelian randomization (MR) in East Asian and European populations, respectively. The data we utilized were obtained from the genome-wide association studies (GWAS) database. Various MR methods, including inverse variance weighted (IVW), MR Egger, weighted median, simple median and simple mode were employed to estimate the association between HBV infection and osteoporosis. Heterogeneity analysis and sensitivity tests were performed to ensure the robustness of the results. Bayesian co-localization (coloc) analysis was also applied to calculate the posterior probability of causal variants and to identify common genetic variants between HBV infection and osteoporosis. Results MR analysis indicated that HBV infection increased the risk of osteoporosis onset in two East Asian cohort (IVW, OR = 1.058, 95% CI = 1.021 to 1.097, P = 0.002 and OR = 1.067, 95% CI = 1.029 to 1.106, P < 0.001). However, a clear effect of genetic susceptibility to HBV on the enhanced risk of osteoporosis was not observed in two European cohort (IVW, OR = 1.000, 95% CI = 0.999 to 1.001, P = 0.171 and OR = 1.003, 95% CI = 0.981 to 1.025, P = 0.780). Additional MR methods and sensitivity analyses further validated the reliability and robustness of our results. Bayesian co-localization analysis revealed co-localization of HBV infection and osteoporosis on STAT4 at rs11889341based on East Asian GWAS data. Conclusions Our study identified a causal relationship between HBV infection and osteoporosis in East Asian and European populations. These results provided strong evidence that HBV infection augmented the risk of developing osteoporosis in East Asian populations and provided novel therapeutic targets.
Collapse
Affiliation(s)
- Zhengnan Li
- Department of Sports Medicine, Ganzhou People’s Hospital, Ganzhou, Jiangxi, China
| | - Jiarui Cao
- Queen Mary School, Medical College, Nanchang University, Nanchang, China
| | - Ke Li
- Queen Mary School, Medical College, Nanchang University, Nanchang, China
| | - Yixin Wu
- Queen Mary School, Medical College, Nanchang University, Nanchang, China
| | - Zhanpeng Luo
- Queen Mary School, Medical College, Nanchang University, Nanchang, China
| | - Rui Cao
- Queen Mary School, Medical College, Nanchang University, Nanchang, China
| | - Zhiheng Cheng
- Queen Mary School, Medical College, Nanchang University, Nanchang, China
| | - Zhendong Tian
- Queen Mary School, Medical College, Nanchang University, Nanchang, China
| | - Yiyang Han
- Queen Mary School, Medical College, Nanchang University, Nanchang, China
| | - Yuping Lai
- The Huankui Academy, Nanchang University, Nanchang, Jiangxi, China
| | - Bangqi Wang
- State Key Laboratory of Molecular Oncology and Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Shen Chen
- The Key Laboratory of Geriatrics, Beijing Institute of Geriatrics, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing Hospital/National Center of Gerontology of National Health Commission, Beijing, China
| |
Collapse
|
5
|
Zhu F, Wang M, Zhang X, Zhao G, Gao H, Zhou L. Contradictory Mechanisms of rheumatoid arthritis and hepatitis B virus infection activation. Heliyon 2025; 11:e41444. [PMID: 39850429 PMCID: PMC11755052 DOI: 10.1016/j.heliyon.2024.e41444] [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: 08/13/2024] [Revised: 11/07/2024] [Accepted: 12/22/2024] [Indexed: 01/25/2025] Open
Abstract
Rheumatoid arthritis (RA) is associated with a high rate of hepatitis B virus (HBV) infection. A large proportion of HBV reactivation may occur in RA patients after immunosuppression treatment, while fulminant hepatitis may occur in severe cases. Immunosuppressants are fundamental medications for the treatment of RA but carry the risk of inducing HBV reactivation. This inherent contradiction poses challenges throughout the immunosuppressive treatment process in patients with RA. Recently, numerous studies have been conducted on the contradictory therapeutic mechanisms between RA treatment and HBV infection, including aspects of innate immunity, adaptive immunity, and related signalling pathways. In this article, we review the immunological mechanisms underlying the onset of RA and HBV infections, providing a reference for determining appropriate treatment plans to reduce therapeutic contradictions and thereby reduce the risk of HBV reactivation in patients with RA combined with HBV infection.
Collapse
Affiliation(s)
- Fenglin Zhu
- Department of Rheumatology, The First Affiliated Hostipal of Chonqqing University of Chinese Medicine, Chongqing, Jiangbei, 410000, China
| | - Miao Wang
- Department of Rheumatology, The First Affiliated Hostipal of Chonqqing University of Chinese Medicine, Chongqing, Jiangbei, 410000, China
| | - Xuhong Zhang
- Department of Rheumatology, Wuxi Hospital of Traditional Chinese Medicine, Wuxi, 214000, Jiangsu, China
| | - Guoqing Zhao
- Department of Rheumatology, Wuxi Hospital of Traditional Chinese Medicine, Wuxi, 214000, Jiangsu, China
| | - Hongyan Gao
- Chongqing Key Laboratory of Traditional Chinese Medicine to Prevent and Treat Autoimmune Diseases, The First Affiliated Hostipal of Chonqqing University of Chinese Medicine, Chongqing, Jiangbei, 410000, China
| | - Lamei Zhou
- Department of Rheumatology, Wuxi Hospital of Traditional Chinese Medicine, Wuxi, 214000, Jiangsu, China
| |
Collapse
|
6
|
Yan F, Tang F, Chen J, Lin Y, Chen X, Du Q, Yin W, Liang J, Liu L, Wang F, Xu B, Ye Q, Xiang H. Exploring using HBsAg to predict interferon treatment course to achieve clinical cure in chronic hepatitis B patients: a clinical study. Front Immunol 2025; 15:1528758. [PMID: 39867915 PMCID: PMC11758162 DOI: 10.3389/fimmu.2024.1528758] [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: 11/15/2024] [Accepted: 12/18/2024] [Indexed: 01/28/2025] Open
Abstract
Objective Although pegylated interferon α-2b (PEG-IFN α-2b) therapy for chronic hepatitis B has received increasing attention, determining the optimal treatment course remains challenging. This research aimed to develop an efficient model for predicting interferon (IFN) treatment course. Methods Patients with chronic hepatitis B, undergoing PEG-IFN α-2b monotherapy or combined with NAs (Nucleoside Analogs), were recruited from January 2018 to December 2023 at Tianjin Third Central Hospital. All patients achieved hepatitis B surface antigen (HBsAg) clearance post-treatment. Result The study enrolled 176 patients with chronic hepatitis B, with the median IFN treatment course of 35.23 ± 25.22 weeks. They were randomly divided into two cohorts in a ratio of 7:3. And there were 123 patients in the training cohort and 53 patients in the validation cohort. Univariable and multivariable analyses demonstrated that baseline HBsAg, 12 weeks HBsAg and the presence of cirrhosis significantly influenced IFN treatment course, and both are risk factors (β=7.27,4.27,10.91; p<0.05). After adjusting for confounding factors, HBsAg remained a significant predictor (β=6.99, 95%CI: 3.59,10.40; p<0.05), which was finally included to establish the model. The actual and predicted values in the validation cohort were highly matched, meanwhile the mean absolute percentage error (MAPE), root mean square error (RMSE) and accuracy (ACC) of the validation cohort were calculated. External validation also suggests that the model can be used as a tool for initial assessment. Conclusion Baseline HBsAg in chronic hepatitis B patients were a risk factor for prolonged IFN treatment course with a positive correlation. Ultimately, a personalized model based on baseline HBsAg levels can be established to roughly estimate the duration of interferon therapy prior to treatment initiation, thereby guiding clinical decision-making.
Collapse
Affiliation(s)
- Fei Yan
- The Third Central Clinical College of Tianjin Medical University, Tianjin Third Central Hospital, Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Institute of Hepatobiliary Disease, Tianjin, China
| | - Fei Tang
- Department of Gastroenterology and Hepatology, Tianjin Third Central Hospital, Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Institute of Hepatobiliary Disease, Tianjin, China
| | - Jing Chen
- The Third Central Clinical College of Tianjin Medical University, Tianjin Third Central Hospital, Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Institute of Hepatobiliary Disease, Tianjin, China
| | - YiCheng Lin
- The Third Central Clinical College of Tianjin Medical University, Tianjin Third Central Hospital, Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Institute of Hepatobiliary Disease, Tianjin, China
| | - XinYu Chen
- The Third Central Clinical College of Tianjin Medical University, Tianjin Third Central Hospital, Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Institute of Hepatobiliary Disease, Tianjin, China
| | - Qin Du
- Nankai University Affiliated Third Center Hospital, Tianjin Third Central Hospital, Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Institute of Hepatobiliary Disease, Tianjin, China
| | - WeiLi Yin
- Department of Gastroenterology and Hepatology, Tianjin Third Central Hospital, Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Institute of Hepatobiliary Disease, Tianjin, China
| | - Jing Liang
- Department of Gastroenterology and Hepatology, Tianjin Third Central Hospital, Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Institute of Hepatobiliary Disease, Tianjin, China
| | - Lei Liu
- Department of Gastroenterology and Hepatology, Tianjin Third Central Hospital, Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Institute of Hepatobiliary Disease, Tianjin, China
| | - Fang Wang
- Department of Gastroenterology and Hepatology, Tianjin Third Central Hospital, Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Institute of Hepatobiliary Disease, Tianjin, China
| | - BaiGuo Xu
- Department of Gastroenterology and Hepatology, Tianjin Third Central Hospital, Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Institute of Hepatobiliary Disease, Tianjin, China
| | - Qing Ye
- Department of Gastroenterology and Hepatology, Tianjin Third Central Hospital, Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Institute of Hepatobiliary Disease, Tianjin, China
| | - HuiLing Xiang
- Department of Gastroenterology and Hepatology, Tianjin Third Central Hospital, Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Institute of Hepatobiliary Disease, Tianjin, China
| |
Collapse
|
7
|
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.
Collapse
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
| |
Collapse
|
8
|
Elgenidy A, Abubasheer TM, Odat RM, Abdelrahim MG, Jibril NS, Ramadan AM, Ballut L, Haseeb ME, Ragab A, Ismail AM, Afifi AM, Mohamed BJ, Jalal PK. Assessing the Predictive Accuracy of the aMAP Risk Score for Hepatocellular Carcinoma (HCC): Diagnostic Test Accuracy and Meta-analysis. J Clin Exp Hepatol 2025; 15:102381. [PMID: 39262566 PMCID: PMC11386263 DOI: 10.1016/j.jceh.2024.102381] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/08/2024] [Accepted: 07/21/2024] [Indexed: 09/13/2024] Open
Abstract
Purpose We aimed to perform a meta-analysis with the intention of evaluating the reliability and test accuracy of the aMAP risk score in the identification of HCC. Methods A systematic search was performed in PubMed, Scopus, Cochrane, Embase, and Web of Science databases from inception to September 2023, to identify studies measuring the aMAP score in patients for the purpose of predicting the occurrence or recurrence of HCC. The meta-analysis was performed using the meta package in R version 4.1.0. The diagnostic accuracy meta-analysis was conducted using Meta-DiSc software. Results Thirty-five studies 102,959 participants were included in the review. The aMAP score was significantly higher in the HCC group than in the non-HCC group, with a mean difference of 6.15. When the aMAP score is at 50, the pooled sensitivity, specificity, negative likelihood ratio, and positive likelihood ratio with 95% CI was 0.961 (95% CI 0.936, 0.976), 0.344 (95% CI 0.227, 0.483), 0.114 (95% CI 0.087, 0.15), and 1.464 (95% CI 1.22, 1.756), respectively. At a cutoff value of 60, the pooled sensitivity, specificity, negative likelihood ratio, and positive likelihood ratio with 95% CI was 0.594 (95% CI 0.492, 0.689), 0.816 (95% CI 0.714, 0.888), 0.497 (95% CI 0.418, 0.591), and 3.235 (95% CI 2.284, 4.582), respectively. Conclusion The aMAP score is a reliable, accurate, and easy-to-use tool for predicting HCC patients of all stages, including early-stage HCC. Therefore, the aMAP score can be a valuable tool for surveillance of HCC patients and can help to improve early detection and reduce mortality.
Collapse
Affiliation(s)
| | - Tareq M Abubasheer
- Faculty of Medicine, Al-Quds University (Al-Azhar Branch), Gaza, Palestine
| | - Ramez M Odat
- Faculty of Medicine, Jordan University of Science and Technology, Irbid, Jordan
| | | | - Nada S Jibril
- Faculty of Medicine, Menofia University, Menofia, Egypt
| | - Aya M Ramadan
- Faculty of Medicine, Menofia University, Menofia, Egypt
| | | | | | | | | | - Ahmed M Afifi
- Department of Surgery, University of Toledo Medical Center, USA
| | - Benarad J Mohamed
- Oncology Department UClouvain, University Catholic Louvain, Brussels, Belgium
| | - Prasun K Jalal
- Division of Gastroenterology, Baylor College of Medicine, Houston, TX, 77030, USA
| |
Collapse
|
9
|
Zhang M, Mouzannar K, Zhang Z, Teraoka Y, Piotrowski J, Ishida Y, Tateno-Mukaidani C, Saito T, Abe-Chayama H, Chayama K, Liang TJ. Hepatitis B virus genotypes A1 and A2 have distinct replication phenotypes due to polymorphisms in the HBx gene. PLoS Pathog 2025; 21:e1012803. [PMID: 39787208 PMCID: PMC11717313 DOI: 10.1371/journal.ppat.1012803] [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: 08/02/2024] [Accepted: 12/03/2024] [Indexed: 01/12/2025] Open
Abstract
HBV genotype A has two major subtypes, A1 (commonly in Africa) and A2 (commonly in Europe) with only 4% nucleotide differences. Individuals infected with these two subtypes appear to have different clinical manifestations and virologic features. Whether such a difference results from the virus or host has not been established. Using HBV generated from molecule clones of subtypes A1 and A2 in cell culture (HBVcc), we demonstrate that HBVcc of subtypes A1 and A2 can be passaged in vitro and in vivo and respond equally well to human IFN-α treatment. HBVcc passaged in human liver chimeric mice (HBVmp) infected human hepatocytes more efficiently than that of the original HBVcc. Subtype A2 showed a much higher viral replication level than that of subtype A1. Mechanistic investigations using constructs with chimeric A1/A2 sequences and specific mutations indicated that subtype A2 has an inherently higher replication phenotype due to specific polymorphisms in the HBx gene resulting in amino acid variations. Studies of HBx expression demonstrated that A1 HBx is expressed at a much lower level than that of A2 HBx. Mutagenesis studies identified two HBx amino acid variations responsible for the observed phenotypic difference. Using AlphaFold2, we generated structural models of HBx proteins of A1 and A2. Superposition of the two models reveal that the overall structural motifs are similarly aligned, except for the C-terminal peptides diverging between the A1 and A2 models, possibly explaining their functional difference. In conclusion, using various in vitro and in vivo models, here we show that subtype A2 has an inherently higher replication phenotype due to polymorphisms in HBx that result in possible differences in structure and expression level of the two subtype HBx proteins. This genotypic difference potentially explains the reported clinical differences between the two subtypes as well as providing a previously unrecognized association between viral sequence variations and clinical manifestations of HBV infection in humans.
Collapse
Affiliation(s)
- Min Zhang
- Liver Diseases Branch, NIDDK, NIH, Bethesda, Maryland, United States of America
| | - Karim Mouzannar
- Liver Diseases Branch, NIDDK, NIH, Bethesda, Maryland, United States of America
| | - Zhensheng Zhang
- Liver Diseases Branch, NIDDK, NIH, Bethesda, Maryland, United States of America
| | - Yuji Teraoka
- Department of Gastroenterology and Metabolism, Graduate School of Biomedical & Health Science, Hiroshima University, Hiroshima, Japan
| | - Jason Piotrowski
- Liver Diseases Branch, NIDDK, NIH, Bethesda, Maryland, United States of America
| | - Yuji Ishida
- Division of Gastrointestinal and Liver Diseases, Department of Medicine, University of Southern California, Keck School of Medicine, Los Angeles, California, United States of America
- PhoenixBio Co., Ltd., Higashi-Hiroshima, Hiroshima, Japan
| | - Chise Tateno-Mukaidani
- Division of Gastrointestinal and Liver Diseases, Department of Medicine, University of Southern California, Keck School of Medicine, Los Angeles, California, United States of America
- PhoenixBio Co., Ltd., Higashi-Hiroshima, Hiroshima, Japan
| | - Takeshi Saito
- Division of Gastrointestinal and Liver Diseases, Department of Medicine, University of Southern California, Keck School of Medicine, Los Angeles, California, United States of America
| | - Hiromi Abe-Chayama
- Center for Medical Specialist Graduate Education and Research, Hiroshima, Japan
| | - Kazuaki Chayama
- Collaborative Research Laboratory of Medical Innovation, Hiroshima University, Hiroshima, Japan
| | - T. Jake Liang
- Liver Diseases Branch, NIDDK, NIH, Bethesda, Maryland, United States of America
| |
Collapse
|
10
|
Bell L, Kalulu A, Ameara K, Allard N, Natuman S, Fisher Z, Homer CS, Taissets A, Jackson K, Karan N, Kalmos K, Deed E, Dick L, Obed L, Toa F, Obed H, Taura BJ, Guyant P, Howell J, Iopa J, Pakoa JG, Paul M, Sam H, Spelman T, Stephens J, Vurobaravu S, Hellard M, van Gemert C. Protektem pikinini blong yu trial: protocol for a single arm field trial to assess the effectiveness of treating-all pregnant women with hepatitis B infection with tenofovir prophylaxis to prevent mother-to-child transmission in Vanuatu, 2024-2025. BMC Public Health 2024; 24:3457. [PMID: 39695524 PMCID: PMC11657636 DOI: 10.1186/s12889-024-20946-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2024] [Accepted: 12/03/2024] [Indexed: 12/20/2024] Open
Abstract
BACKGROUND Hepatitis B infection is a major public health concern in Vanuatu, with approximately 9% of the general population estimated to be living with chronic hepatitis B. Most new infections are due to mother-to-child transmission (MTCT). Hepatitis B vaccination is available in Vanuatu, but coverage rates for first dose within 24 h of birth and third dose are suboptimal. While treatment of chronic hepatitis B infection with tenofovir disoproxil fumarate (TDF) is available in country, there is no capacity to test hepatitis B e antigen and limited capacity to test hepatitis B virus (HBV) DNA viral load, which is a current eligibility requirement for women in pregnancy to access hepatitis B prophylaxis for MTCT per National guidelines. Recently, the World Health Organization guidelines have been updated to recommend universal peripartum antiviral prophylaxis (PAP) of pregnant women living with hepatitis B to prevent MTCT of HBV, without assessment of viral load in places without access to testing. However, these recommendations are conditional based on low-certainty evidence. The aim of this trial is to evaluate the effectiveness and safety of universal PAP and provide evidence for the global guidelines. METHODS A single arm field trial compared to real world control sites will be conducted in Vanuatu involving pregnant women attending antenatal care services with positive HBsAg rapid tests. Participants at the control sites will undergo routine care. Participants at the intervention sites will all receive oral TDF prophylaxis from second trimester to completion of infant primary hepatitis B vaccination schedule. Primary data analysis will be by intention-to-treat. Initial analyses will be unadjusted comparisons of the intervention sites and control sites. Adjusted analyses will be performed, as needed, and presented in addition to unadjusted comparisons. DISCUSSION This study will provide evidence of acceptability, effectiveness and cost-effectiveness of prophylaxis for all women with hepatitis B during pregnancy, as per the updated WHO guidelines, compared with current practice. The outcome of this trial will provide critical information to inform national and global guidelines around universal peripartum antiviral prophylaxis for hepatitis B during pregnancy. TRIAL REGISTRATION Australian New Zealand Clinical Trials Registry (ANZCTR), ACTRN: ACTRN12623001202651p. Registered 21 November 2023.
Collapse
Affiliation(s)
- Leila Bell
- Burnet Institute, Melbourne, Australia.
- Monash University, Melbourne, Australia.
| | | | | | - Nicole Allard
- Department of Infectious Diseases, University of Melbourne, Melbourne, Australia
- WHO Collaborating Centre for Viral Hepatitis, The Doherty Institute, Melbourne, Australia
| | | | | | - Caroline Se Homer
- Burnet Institute, Melbourne, Australia
- Monash University, Melbourne, Australia
| | | | - Kathy Jackson
- Victorian Infectious Diseases Reference Laboratory, Royal Melbourne Hospital, at the Peter Doherty Institute for Infection and Immunity, Victoria, 3000, Australia
| | - Navin Karan
- Victorian Infectious Diseases Reference Laboratory, Royal Melbourne Hospital, at the Peter Doherty Institute for Infection and Immunity, Victoria, 3000, Australia
| | | | - Emily Deed
- London School of Hygiene and Tropical Medicine, London, UK
| | - Leiwia Dick
- Laboratory Department, Vila Central Hospital, Port Vila, Vanuatu
| | - Leias Obed
- Vanuatu Family Health Association, Port Vila, Vanuatu
| | | | | | | | | | - Jessica Howell
- Burnet Institute, Melbourne, Australia
- Monash University, Melbourne, Australia
- Department of Gastroenterology, St. Vincent's Hospital, Melbourne, Australia
- Department of Medicine, University of Melbourne, Melbourne, Australia
| | | | | | - Minado Paul
- Vila Central Hospital General Medicine, Port Vila, Vanuatu
| | | | - Tim Spelman
- Burnet Institute, Melbourne, Australia
- Department of Surgery, University of Melbourne, Melbourne, Australia
| | | | | | - Margaret Hellard
- Burnet Institute, Melbourne, Australia
- Monash University, Melbourne, Australia
- Department of Infectious Diseases, The Alfred Hospital, Melbourne, Australia
- Doherty Institute and School of Population and Global Health, University of Melbourne, Melbourne, Australia
| | | |
Collapse
|
11
|
Yan B, Zhang X, Lv J, Feng Y, Meng X, Lin X, Zhang Y, Wang S, Ji F, Chen M, Yuan X, Tao Z, Zhang L. Seroprevalence of hepatitis B among the general population in Shandong Province, Eastern China, an update 30 years after the implementation of the neonatal vaccination program. BMC Infect Dis 2024; 24:1433. [PMID: 39695996 DOI: 10.1186/s12879-024-10340-0] [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: 08/27/2024] [Accepted: 12/11/2024] [Indexed: 12/20/2024] Open
Abstract
BACKGROUND In 1992, Hepatitis B vaccine was first recommended for routine neonatal immunization in China. This study aimed to estimate the prevalence of hepatitis B virus (HBV) infection in Shandong Province, eastern China (updating our previous study in 2014), and to help guide the efforts of hepatitis B elimination. METHODS We determined prevalence of HBV infection from the remaining serum samples collected through a population-based survey, which was originally intended for a seroepidemiological survey of anti-SARS-CoV-2 antibodies conducted in 2023. The samples (n = 5000) were obtained from individuals all-aged over 1 year residing in ten counties of Shandong Province. The chemiluminescence microparticle immunoassay was used to detect serological markers of HBV. RESULTS In total, 4999 samples were eligible for the test of hepatitis B. The overall prevalence of HBsAg, anti-HBs, and anti-HBc in the 2023 survey was 2.25% (95%CI:1.64-2.87), 46.21% (95%CI:44.05-48.38), and 25.17% (95%CI:23.46-26.88), respectively. The HBsAg prevalence has dropped to 0.28% among individuals younger than 30 years, particularly with less than 0.1% among children aged 1-14 (considerably below the 8% prevalence recorded in 1992). The peak prevalence of HBsAg was observed in individuals aged 40-49 years (5.63%), followed by those aged 30-39 (3.11%). CONCLUSION The Shandong Province has achieved substantial success in controlling HBV infection among the younger generation through the newborn routine vaccination program. To accelerate progress towards the goal of eliminating hepatitis B in the province, additional strategies should also be adopted in parallel, including increasing diagnostic coverage, expanding antiviral treatment, and enhancing hepatitis B vaccine coverage for HBV-susceptible adults.
Collapse
Affiliation(s)
- Bingyu Yan
- Shandong Center for Disease Control and Prevention, Jinan, China
| | - Xiaomeng Zhang
- School of Public Health, Shandong University Cheeloo College of Medicine, Jinan, China
| | - Jingjing Lv
- Shandong Center for Disease Control and Prevention, Jinan, China
| | - Yi Feng
- Shandong Center for Disease Control and Prevention, Jinan, China
| | - Xin Meng
- Shandong Center for Disease Control and Prevention, Jinan, China
| | - Xiaojuan Lin
- Shandong Center for Disease Control and Prevention, Jinan, China
| | - Yan Zhang
- Shandong Center for Disease Control and Prevention, Jinan, China
| | - Suting Wang
- Shandong Center for Disease Control and Prevention, Jinan, China
| | - Feng Ji
- Shandong Center for Disease Control and Prevention, Jinan, China
| | - Meng Chen
- Shandong Center for Disease Control and Prevention, Jinan, China
| | - Xinyu Yuan
- Shandong Center for Disease Control and Prevention, Jinan, China
| | - Zexin Tao
- Shandong Center for Disease Control and Prevention, Jinan, China
| | - Li Zhang
- Shandong Center for Disease Control and Prevention, Jinan, China.
- School of Public Health, Shandong University Cheeloo College of Medicine, Jinan, China.
| |
Collapse
|
12
|
Zoa-Assoumou S, M'boyis-Kamdem H, Mougola-Bissiengou P, Nzengui-Nzengui GF, Kombila-Koumavor C, Mbani-Okouma M, Mourembou G, Ndjoyi-Mbiguino A. Seroprevalence of hepatitis B virus markers of infection and immunity among people living in Libreville, Gabon. IJID REGIONS 2024; 13:100448. [PMID: 39885836 PMCID: PMC11780383 DOI: 10.1016/j.ijregi.2024.100448] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/22/2024] [Revised: 09/06/2024] [Accepted: 09/06/2024] [Indexed: 02/01/2025]
Abstract
Objectives In Gabon, data on hepatitis B virus (HBV) infection are limited to hepatitis B surface antigen (HBsAg) detection among specific populations and rural regions. This is the first study aimed at determining the seroprevalence of HBV markers among the Gabonese population. Methods A retrospective study was conducted from January 2002 through December 2022. All patients who requested HBV marker screening (HBsAg, anti-HBc, anti-HBs, anti-HBe, hepatitis B e antigen) were included in this study. Results A total of 496 people were included in this study. The prevalence of HBV exposure was high (59.5%) and significantly associated with age, sex, pregnancy status, and social status. Among individuals with evidence of HBV exposure, only 89 (33.7%) had effectively cleared the virus. Overall, HBsAg was detected in 108 of the 496 (21.8%) people included in the study. HBsAg infection was more common among individuals in the 16-25 (35.1%) and 26-35-year (30.6%) age groups. Moreover, most of HBsAg-infected patients were health care workers (HCWs) (P = 0.0096). Among the 496 individuals included in this study, 126 (25.4%) were still susceptible to HBV. Most of the susceptible female patients were pregnant (P <0.0001). HCWs had a significantly lower probability of being naïve to HBV infection (P = 0.0001). There was a similar prevalence of susceptibility in male and female patients (50 [24.5%] male and 76 [26.0%] female patients). Only 15.1% of the studied population was vaccinated. Conclusions Our findings revealed a high seroprevalence of HBV infection in the study area and very low HBV immunization coverage. Additional care and resources should be provided to promote HBV vaccination and block vertical HBV transmission.
Collapse
Affiliation(s)
- Samira Zoa-Assoumou
- University of Health Sciences, Department of Bacteriology-Virology, Libreville, Gabon
- University of Hassan II Casablanca, Faculty of Sciences and Technologies Mohammedia, Laboratory of Virology, Microbiology and Quality/Ecotoxicology and Biodiversity, Casablanca, Morocco
| | - Hervé M'boyis-Kamdem
- University of Health Sciences, Department of Bacteriology-Virology, Libreville, Gabon
| | | | | | | | - Marina Mbani-Okouma
- University of Health Sciences, Department of Bacteriology-Virology, Libreville, Gabon
| | - Gael Mourembou
- University of Health Sciences, Department of Bacteriology-Virology, Libreville, Gabon
| | | |
Collapse
|
13
|
Okwan DK, Scott GY, Takyi P, Boateng CO, Antwi PB, Abrampah AA, Boateng DGKO, Obeng MA. A Multicentre Cross-Sectional Study on Hepatitis B Vaccination Coverage and Associated Factors Among Personnel Working in Health Facilities in Kumasi, Ghana. BIOMED RESEARCH INTERNATIONAL 2024; 2024:8899638. [PMID: 39534102 PMCID: PMC11557171 DOI: 10.1155/2024/8899638] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 08/14/2024] [Accepted: 10/18/2024] [Indexed: 11/16/2024]
Abstract
Background: As part of efforts to reach the elimination target by 2030, the WHO and CDC recommend that all HCWs adhere to the three-dose Hepatitis B vaccination schedule to protect themselves against the infection. This study assessed Hepatitis B vaccination coverage and associated factors among personnel working in health facilities in Kumasi, Ashanti Region, Ghana. Materials and Methods: A cross-sectional study involving 530 HCWs was conducted in four hospitals in Kumasi from September to November 2023. An investigator-administered questionnaire was employed in gathering participant demographics and other information related to vaccination coverage. IBM SPSS Version 26.0 and GraphPad Prism 8.0 were used for analysing the data. Results: Even though the majority (70.6%) reported having taken at least one dose of the vaccine, only 43.6% were fully vaccinated (≥ 3 doses). More than a quarter (29.4%) had not taken any dose of the HBV vaccine. Close to a quarter (23.6%) had not screened or tested for HBV infection in their lifetime. The statistically significant variables influencing vaccination status were age, marital status, profession, and status in the hospital. Nearly one-half (44.9%) of the participants who have not taken the vaccine reported they do not have a reason for not taking it, and a high proportion (80.1%) were willing to take the vaccine when given for free. Conclusion: To combat the low Hepatitis B vaccination coverage among healthcare workers in Kumasi, Ghana, amidst the significant public health threat of HBV infection, comprehensive measures are necessary. These include implementing infection prevention control programmes, enhancing occupational health and safety, and conducting health promotion campaigns in healthcare facilities. Extending and intensifying Hepatitis B screening and vaccination initiatives to tertiary institutions and encouraging employers, supervisors, or team leaders to provide these services nationwide are also recommended.
Collapse
Affiliation(s)
- Daniel Kobina Okwan
- Department of Anatomy, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana
| | - Godfred Yawson Scott
- Department of Medical Diagnostics, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana
| | - Pius Takyi
- Kumasi Centre for Collaborative Research in Tropical Medicine, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana
| | - Clinton Owusu Boateng
- Kumasi Centre for Collaborative Research in Tropical Medicine, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana
| | - Philemon Boasiako Antwi
- Kumasi Centre for Collaborative Research in Tropical Medicine, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana
| | | | | | - Michael Agyemang Obeng
- Kumasi Centre for Collaborative Research in Tropical Medicine, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana
| |
Collapse
|
14
|
Angelo AA, Teketelew BB, Berta DM, Chane E, Cherie N, Nigus M, Girmay G, Tamir M, Bitew M. Knowledge, attitude, and practices towards hepatitis infection and its associated factors among adults in Gondar town, northwest Ethiopia; a community-based study, 2021. JOURNAL OF HEALTH, POPULATION, AND NUTRITION 2024; 43:178. [PMID: 39497180 PMCID: PMC11536916 DOI: 10.1186/s41043-024-00654-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/27/2024] [Accepted: 10/04/2024] [Indexed: 11/06/2024]
Abstract
BACKGROUND Hepatitis virus infection remains a serious public health concern worldwide. Percutaneous, mucosal, or non-intact skin exposure to infectious blood, semen, and other body fluids are the major routes of infection in endemic areas, including Ethiopia, where little is known about the community's knowledge, attitudes, and practice toward hepatitis infection. Thus, this study aimed to determine the knowledge, attitude, and practices towards hepatitis infection among adults in Gondar town. METHODS A community-based cross-sectional study was conducted from July to August 2021 on a total of 390 participants. Proportional sample allocation was used in 3 randomly selected sub-cities. Then, study participants from randomly selected households were recruited by using a systematic random sampling technique. Socio-demographic data and questions regarding KAP were collected via a self-administered and interviewer-administered questionnaire. Statistical analysis was performed using SPSS version 20. Logistic regression analyses were used to identify the associated factors and a p-value < 0.05 was considered statistically significant. RESULTS The mean age of the study participants was 30 ± 8.43 years and more than half ½ (53.3%) ranged from 26 to 40 years old. In this study, 335 (85.9%) of study participants had poor knowledge about hepatitis infection. About 344 (88.2%) had a negative attitude toward hepatitis infections, and 344 (88.2%) of the participants had a poor practice to prevent hepatitis infections. Multivariate analysis affirmed that having vaccination for hepatitis infection was significantly associated with a positive attitude (AOR, with 95% CI: 2.135 (1.006-4.532) and good practice levels (AOR, with 95% CI: 22.623 (0.032-0.156). CONCLUSIONS AND RECOMMENDATIONS In this study majority of the participants have poor knowledge, attitudes, and practices toward hepatitis infection. Therefore, targeted community-based interventions are necessary. However, this study revealed that having vaccination for hepatitis infection was significantly associated with a positive attitude and good practice levels among the study participants.
Collapse
Affiliation(s)
- Abiy Ayele Angelo
- Department of Immunology and Molecular Biology, School of Biomedical and Laboratory Sciences, College of Medicine and Health Sciences, University of Gondar, P.O. Box 196, Gondar, Ethiopia.
| | - Bisrat Birke Teketelew
- Department of Hematology and Immunohematology, School of Biomedical and Laboratory Sciences, College of Medicine and Health Sciences, University of Gondar, Gondar, Ethiopia
| | - Dereje Mengesha Berta
- Department of Hematology and Immunohematology, School of Biomedical and Laboratory Sciences, College of Medicine and Health Sciences, University of Gondar, Gondar, Ethiopia
| | - Elias Chane
- Department of Clinical Chemistry, School of Biomedical and Laboratory Sciences, College of Medicine and Health Sciences, University of Gondar, Gondar, Ethiopia
| | - Negesse Cherie
- Department of Quality Assurance and Laboratory Management, School of Biomedical and Laboratory Sciences, College of Medicine and Health Sciences, University of Gondar, Gondar, Ethiopia
| | - Mesele Nigus
- Department of Quality Assurance and Laboratory Management, School of Biomedical and Laboratory Sciences, College of Medicine and Health Sciences, University of Gondar, Gondar, Ethiopia
| | - Getu Girmay
- Department of Immunology and Molecular Biology, School of Biomedical and Laboratory Sciences, College of Medicine and Health Sciences, University of Gondar, P.O. Box 196, Gondar, Ethiopia
| | - Mebratu Tamir
- Department of Medical Parasitology, School of Biomedical and Laboratory Sciences, College of Medicine and Health Sciences, University of Gondar, Gondar, Ethiopia
| | - Mehari Bitew
- Department of Medical Microbiology, School of Biomedical and Laboratory Sciences, College of Medicine and Health Sciences, University of Gondar, Gondar, Ethiopia
| |
Collapse
|
15
|
Tang Y, Xu M, Wang C, Wu M, Hu L, Li J, Lu W, Zheng Y, Zhang M, Jiang X, Zhu C, Audsley J, Tangkijvanich P, Avihingsanon A, Song S, Liu S, Lewin SR, George J, Douglas MW, Ling Y, Yuan Z, Zhu L, Zhang Z, Zhang X. Circulating capsid-antibody-complexes (CACs) drive intrahepatic complement deposition and inform subclinical liver inflammation in chronic hepatitis B. Antiviral Res 2024; 231:106017. [PMID: 39396554 DOI: 10.1016/j.antiviral.2024.106017] [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: 08/14/2024] [Revised: 09/20/2024] [Accepted: 10/04/2024] [Indexed: 10/15/2024]
Abstract
Chronic infection with Hepatitis B Virus (HBV) often results in a dysfunctional virus-specific T cell response hampering viral clearance. Paradoxically, intrahepatic inflammatory responses that contribute more to liver histopathology than to viral suppression are commonly observed, which are widely believed to be cell mediated. The involvement of humoral immunity in this process however is not well documented. To investigate the possible roles of HBV Capsid-Antibody Complexes (CACs) in eliciting chronic liver inflammation, we developed a novel microplate-based assay for the quantification of CACs in serum. The CACs assay showed high sensitivity and specificity with its readout closely correlating with the molecular features of CACs. A cross-sectional study on untreated chronic hepatitis B (CHB) patients showed a 77% positive rate for CACs with significant association with alanine transaminase (ALT), intrahepatic inflammation, and complement deposition, suggestive of its functional role in hepatic injury. Multiple staining of complement activation fragment C4d with major leukocyte and myofibroblast markers revealed an intertwined picture in periportal area with a morphology reminiscent of "piecemeal necrosis". In a pooled cohort with ALT levels lower than 40 IU/ml, CACs alone revealed subclinical liver inflammation. We provide definitive evidence for a causative role for CACs in complement-mediated intrahepatic immunopathology, an additional mechanism contributing to liver damage in CHB. Assessment of CACs in serum complements current clinical markers for assessing CHB associated inflammation.
Collapse
Affiliation(s)
- Yijie Tang
- Shanghai Public Health Clinical Centre, Fudan University, Shanghai, China; Department of Clinical Laboratory Medicine, Shanghai Skin Disease Hospital, School of Medicine, Tonji University, Shanghai, China
| | - Mingzhu Xu
- Shanghai Public Health Clinical Centre, Fudan University, Shanghai, China; Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai, China
| | - Cong Wang
- Shanghai Public Health Clinical Centre, Fudan University, Shanghai, China
| | - Min Wu
- Shanghai Public Health Clinical Centre, Fudan University, Shanghai, China
| | - Lyuyin Hu
- Faculty of Science and Technology, University of Canberra, Australia
| | - Jin Li
- Department of Infectious Diseases, The Affiliated Infectious Diseases Hospital of Soochow University, Suzhou, Jiangsu Province, China
| | - Wei Lu
- Shanghai Public Health Clinical Centre, Fudan University, Shanghai, China
| | - Ye Zheng
- Shanghai Public Health Clinical Centre, Fudan University, Shanghai, China
| | - Min Zhang
- Shanghai Public Health Clinical Centre, Fudan University, Shanghai, China
| | - Xizi Jiang
- Department of Infectious Diseases, The Affiliated Infectious Diseases Hospital of Soochow University, Suzhou, Jiangsu Province, China
| | - Chuanwu Zhu
- Department of Infectious Diseases, The Affiliated Infectious Diseases Hospital of Soochow University, Suzhou, Jiangsu Province, China
| | - Jennifer Audsley
- Department of Infectious Diseases, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia
| | - Pisit Tangkijvanich
- Center of Excellence in Hepatitis and Liver Cancer, Faculty of Medicine, Chulalongkorn University, Thailand
| | - Anchalee Avihingsanon
- HIV Netherlands Australia Thailand Research Collaboration (HIV-NAT), Bangkok, Thailand
| | - Shu Song
- Shanghai Public Health Clinical Centre, Fudan University, Shanghai, China
| | - Shuangzhe Liu
- Faculty of Science and Technology, University of Canberra, Australia
| | - Sharon R Lewin
- Department of Infectious Diseases, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia; Victorian Infectious Diseases Service, Royal Melbourne Hospital at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia; Department of Infectious Diseases, Alfred Hospital and Monash University, Melbourne, Australia
| | - Jacob George
- The Westmead Institute for Medical Research, University of Sydney and Westmead Hospital, Sydney, Australia
| | - Mark W Douglas
- The Westmead Institute for Medical Research, University of Sydney and Westmead Hospital, Sydney, Australia; Centre for Infectious Diseases and Microbiology, Sydney Infectious Diseases Institute, The University of Sydney at Westmead Hospital, Sydney, Australia
| | - Yun Ling
- Shanghai Public Health Clinical Centre, Fudan University, Shanghai, China
| | - Zhenghong Yuan
- Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai, China
| | - Li Zhu
- Department of Infectious Diseases, The Affiliated Infectious Diseases Hospital of Soochow University, Suzhou, Jiangsu Province, China.
| | - Zhanqing Zhang
- Shanghai Public Health Clinical Centre, Fudan University, Shanghai, China.
| | - Xiaonan Zhang
- Shanghai Public Health Clinical Centre, Fudan University, Shanghai, China; Faculty of Science and Technology, University of Canberra, Australia.
| |
Collapse
|
16
|
You X, Jiang F, Zhang Y. Clinical effects of combined treatment of traditional Chinese medicine and western medicine for viral hepatitis B cirrhosis and the effects on serum miR-122, miR-200a. Biotechnol Genet Eng Rev 2024; 40:2803-2817. [PMID: 37057745 DOI: 10.1080/02648725.2023.2202531] [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: 02/22/2023] [Accepted: 04/10/2023] [Indexed: 04/15/2023]
Abstract
The aim is to explore the clinical effects of combined treatment of Traditional Chinese Medicine (TCM) and western medicine in viral hepatitis B cirrhosis and the effects on microRNA (miR)-122 and miR-200a. 116 patients with chronic hepatitis B cirrhosis were admitted to our hospital. Real-time fluorescent quantitative PCR (qPCR) was employed to reveal the level of serum miR-122 and miR-200a in the three groups. The clinical effects of the two groups were compared, including alanine aminotransferase (ALT), aspartate amino transferase (AST), total bilirubin (TBIL) and alpha fetoprotein (AFP) indexes, coagulation function indexes, liver elasticity value and the main therapeutic effects. After treatment, the ALT, AST, TBIL and AFP indexes significantly decreased in both groups, which were much lower in the western medicine (WM) + TCM Group. The levels of albumin (ALB) all increased, and the increase was more significant in the WM + TCM Group. The prothrombin time (PT) was down-regulated while the prothrombin activity (PTA) was up-regulated in both groups. Both groups showed a decrease in liver elasticity after treatment, which was more obvious in the WM + TCM Group. The incidence of primary peritonitis, hepatic encephalopathy, hepatorenal syndrome, gastrointestinal bleeding and electrolyte disturbance in the WM + TCM Group was significantly lower than those in the WM Group. The combination of Chinese and western medicine in the treatment of cirrhosis can reduce the occurrence of complications, improve the clinical symptoms and improve the clinical effects effectively, which is worthy of further study and clinical popularization. Viral hepatitis B, Liver cirrhosis, Combination of TCM and Western medicine, miR-122, miR-200a.
Collapse
Affiliation(s)
- Xiaofan You
- Department of Clinical Laboratory, Yantaishan Hospital, Yantai, China
| | - Fen Jiang
- Department of Hepatology, Yantai Qishan Hospital, Yantai, China
| | - Yiliang Zhang
- Department of Clinical Laboratory, Yantaishan Hospital, Yantai, China
| |
Collapse
|
17
|
Xu W, Luo Q, Zhang Y, Xie C, Peng L. A case report: cccDNA and pgRNA remain positive in liver tissue in a chronic hepatitis B patient with functional cure. Front Med (Lausanne) 2024; 11:1427043. [PMID: 39534217 PMCID: PMC11554451 DOI: 10.3389/fmed.2024.1427043] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2024] [Accepted: 10/11/2024] [Indexed: 11/16/2024] Open
Abstract
Hepatitis B surface antigen (HBsAg) seroclearance is recommended as the ideal endpoint for nucleos(t)ide analog (NA) treatments. Functional cure of chronic hepatitis B (CHB) is defined as having undetectable serum hepatitis B virus (HBV) deoxyribonucleic acid and serum HBsAg. We report a functional cure case of CHB with a family history of hepatocellular carcinoma (HCC) after long-term NA therapy. Despite achieving functional cure for over 7 years, both HBV covalently closed circular deoxyribonucleic acid (cccDNA) and pregenomic ribonucleic acid (pgRNA) remain positive in the liver tissue of the patient, indicating that a sterilizing cure has not been achieved. This case highlights the importance of active surveillance of HBV cccDNA and pgRNA for sterilizing the cure and risk of HCC.
Collapse
Affiliation(s)
- Wenxiong Xu
- Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
- Guangdong Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Qiumin Luo
- Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
- Guangdong Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Yeqiong Zhang
- Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
- Guangdong Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Chan Xie
- Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
- Guangdong Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Liang Peng
- Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
- Guangdong Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
- Key Laboratory of Tropical Disease Control, Ministry of Education, Sun Yat-sen University, Guangzhou, China
| |
Collapse
|
18
|
Echevarria-Lima J, Moles R. Monocyte and Macrophage Functions in Oncogenic Viral Infections. Viruses 2024; 16:1612. [PMID: 39459945 PMCID: PMC11512331 DOI: 10.3390/v16101612] [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] [Revised: 10/07/2024] [Accepted: 10/08/2024] [Indexed: 10/28/2024] Open
Abstract
Monocytes and macrophages are part of innate immunity and constitute the first line of defense against pathogens. Bone marrow-derived monocytes circulate in the bloodstream for one to three days and then typically migrate into tissues, where they differentiate into macrophages. Circulatory monocytes represent 5% of the nucleated cells in normal adult blood. Following differentiation, macrophages are distributed into various tissues and organs to take residence and maintain body homeostasis. Emerging evidence has highlighted the critical role of monocytes/macrophages in oncogenic viral infections, mainly their crucial functions in viral persistence and disease progression. These findings open opportunities to target innate immunity in the context of oncogenic viruses and to explore their potential as immunotherapies.
Collapse
Affiliation(s)
- Juliana Echevarria-Lima
- Laboratório de Imunologia Básica e Aplicada, Department of Immunology, Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro 21941-902, Brazil;
| | - Ramona Moles
- Department of Cell and Molecular Biology, University of Mississippi Medical Center, Jackson, MS 39216, USA
- Cancer Center and Research Institute, University of Mississippi Medical Center, Jackson, MS 39216, USA
- Center for Immunology and Microbial Research, University of Mississippi Medical Center, Jackson, MS 39216, USA
| |
Collapse
|
19
|
Dutschke A, Agergaard J, Medina C, Hønge BL. Prevalence of hepatitis and HIV infection among 18-months old children in Guinea-Bissau before vaccination. Trop Med Int Health 2024; 29:919-921. [PMID: 39187275 DOI: 10.1111/tmi.14045] [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] [Indexed: 08/28/2024]
Abstract
OBJECTIVES This study reports on the prevalence of hepatitis B virus (HBV) in children in Guinea-Bissau before the hepatitis B vaccine was introduced. METHODS Cross-sectional study. From 2005 to 2008, 187 children aged 18 months were enrolled in a vaccine trial and had blood samples taken to test for HBV (HbsAg, anti-HBs and anti-HBc), hepatitis C virus (HCV) and HIV. RESULTS HBsAg prevalence was 11.2% and prevalence of any HBV serological marker was 16.0%. No children were positive for HCV. One was positive for HIV-1. CONCLUSIONS The prevalence of HBsAg was high compared to other sub-Saharan African countries pre-immunisation, underscoring the importance of broad and sustained HBV vaccination. This study indicates that the majority of HBV transmission is horizontal during childhood in Guinea-Bissau.
Collapse
Affiliation(s)
- Alexander Dutschke
- Department of Infectious Diseases, Aarhus University Hospital, Aarhus, Denmark
- Bandim Health Project, Indepth Network, Bissau, Guinea-Bissau
- GloHAU, Center for Global Health, School of Public Health, Aarhus University, Aarhus, Denmark
| | - Jane Agergaard
- Department of Infectious Diseases, Aarhus University Hospital, Aarhus, Denmark
| | - Candida Medina
- Bandim Health Project, Indepth Network, Bissau, Guinea-Bissau
| | - Bo Langhoff Hønge
- Department of Infectious Diseases, Aarhus University Hospital, Aarhus, Denmark
- Bandim Health Project, Indepth Network, Bissau, Guinea-Bissau
| |
Collapse
|
20
|
Thakur S, Goncalves RV. The State of the Globe: The Global Challenge of Hepatitis B and C Coinfection. J Glob Infect Dis 2024; 16:125-126. [PMID: 39886093 PMCID: PMC11775396 DOI: 10.4103/jgid.jgid_219_24] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2024] [Revised: 12/03/2024] [Accepted: 12/03/2024] [Indexed: 02/01/2025] Open
Affiliation(s)
- Suman Thakur
- Department of Emergency Medicine, IGMC, Shimla, Himachal Pradesh, India
| | - Rose V. Goncalves
- Department of Emergency Medicine, Emergency Medicine Residency Program, Sarasota Memorial Hospital, Florida State University College of Medicine, Sarasota, FL, USA
| |
Collapse
|
21
|
Moe KT, Tan KSW. Mechanistic Insights on Microbiota-Mediated Development and Progression of Esophageal Cancer. Cancers (Basel) 2024; 16:3305. [PMID: 39409925 PMCID: PMC11475040 DOI: 10.3390/cancers16193305] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2024] [Revised: 09/18/2024] [Accepted: 09/24/2024] [Indexed: 10/20/2024] Open
Abstract
Esophageal cancer (EC) is one of the most common malignant tumors worldwide, and its two major types, esophageal adenocarcinoma (EAC) and esophageal squamous cell carcinoma (ESCC), present a severe global public health problem with an increasing incidence and mortality. Established risk factors include smoking, alcohol consumption, and dietary habits, but recent research has highlighted the substantial role of oral microbiota in EC pathogenesis. This review explores the intricate relationship between the microbiome and esophageal carcinogenesis, focusing on the following eight significant mechanisms: chronic inflammation, microbial dysbiosis, production of carcinogenic metabolites, direct interaction with epithelial cells, epigenetic modifications, interaction with gastroesophageal reflux disease (GERD), metabolic changes, and angiogenesis. Certain harmful bacteria, such as Porphyromonas gingivalis and Fusobacterium nucleatum, are specifically implicated in sustaining irritation and tumor progression through pathways including NF-κB and NLRP3 inflammasome. Additionally, the review explores how microbial byproducts, including short-chain fatty acids (SCFAs) and reactive oxygen species (ROS), contribute to DNA harm and disease advancement. Furthermore, the impact of reflux on microbiota composition and its role in esophageal carcinogenesis is evaluated. By combining epidemiological data with mechanistic understanding, this review underscores the potential to target the microbiota-immune system interplay for novel therapeutic and diagnostic strategies to prevent and treat esophageal cancer.
Collapse
Affiliation(s)
- Kyaw Thu Moe
- Biomedical Sciences, Newcastle University Medicine Malaysia, Iskandar Puteri 79200, Johor, Malaysia
| | - Kevin Shyong-Wei Tan
- Laboratory of Molecular and Cellular Parasitology, Health Longevity Translational Research Programme, Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, 5 Science Drive, Singapore 117545, Singapore
| |
Collapse
|
22
|
Senoo-Dogbey VE, Klutsey EE. Self-reported exposure to blood and body fluids and serological evidence of lifetime exposure to hepatitis B virus among health care workers in Ghana: a cross-sectional study. BMC Infect Dis 2024; 24:968. [PMID: 39271979 PMCID: PMC11396757 DOI: 10.1186/s12879-024-09703-4] [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: 03/22/2024] [Accepted: 08/01/2024] [Indexed: 09/15/2024] Open
Abstract
INTRODUCTION In Sub-Saharan Africa alone, about 40-65% of Hepatitis B Virus infections among HCWs were a result of percutaneous occupational exposures to contaminated blood and body fluids of patients. Occupational exposure to blood and body fluids among healthcare workers is on the rise in Ghana. However, the relationship between self-reported exposures to blood and body fluids suspected to be contaminated with the hepatitis B virus and actual serological evidence of exposure remains unknown. The aim of the study however was to assess the self-reported exposure to HBV as against the serological evidence of lifetime exposure to HBV and associated factors among Ghanaian HCWs. METHODS The study was a cross-sectional analytical survey that involved 340 HCWs who were recruited using a simple random sampling procedure from six cadres of staff from five districts in Greater Accra. The participants were surveyed using a validated instrument and 5mls of venous blood was aseptically withdrawn for qualitative detection of Anti-HBc. SPSS version 23.0 was used to analyze the data to obtain proportions, odds ratios and their corresponding confidence intervals with the level of significance set at 0.05. RESULTS The response rate was 94% with Nurses and Doctors in the majority with a mean age of 35.6 ± 7.2. Self-reported exposure to HBV was 63% whereas lifetime exposure to HBV (Anti-HBc) prevalence was 8.2% (95% CI = 5.0-11.0%). Females were 60% less likely to be exposed to HBV (aOR = 0.4; 95% CI = 0.1-0.9) than their male counterparts. HCWs without training in the prevention of blood-borne infections had almost three times higher odds of being exposed to HBV in their lifetime (aOR = 2.6; 95% CI = 1.0-6.4). CONCLUSIONS The findings of this study suggest that self-reported exposure to HBV-contaminated biological materials was high with a corresponding high lifetime exposure to HBV. The female gender was protective of anti-HBc acquisition. Apart from direct interventions for preventing occupational exposures to HBV in the healthcare setting, periodic training of all categories of healthcare workers in infection prevention techniques could significantly reduce exposure to the Hepatitis B virus.
Collapse
Affiliation(s)
- Vivian Efua Senoo-Dogbey
- Department of Public Health, School of Nursing and Midwifery, University of Ghana, P. O. Box LG 25, Accra, Legon, Ghana.
- Ghana Institute of Management and Public Administration, Greenhill Campus Achimota, Accra, Ghana.
| | - Ellen Eyi Klutsey
- Department of Nursing, University of Health and Allied Sciences, Ho, Volta Region, Ghana
| |
Collapse
|
23
|
Awiah EA, Aabalekuu S, Dun-Dery F, Dun-Dery E, Bayor F, Adokiya MN, Bessing B. Correlates of Hepatitis B infection in pregnant women attending antenatal clinics in Wa Municipality, Ghana. PLOS GLOBAL PUBLIC HEALTH 2024; 4:e0002447. [PMID: 39255265 PMCID: PMC11386425 DOI: 10.1371/journal.pgph.0002447] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/14/2023] [Accepted: 08/13/2024] [Indexed: 09/12/2024]
Abstract
Despite the availability of an effective vaccine against viral hepatitis B infection, it remains prevalent, highly transmissible especially through mother-to-child, life-threatening, and a major public health challenge. A positive Hepatitis B e-Antigen (HBeAg) mother has a 90% risk of transmitting the virus to the unborn child in the perinatal period. This study sought to determine the prevalence and risk of Hepatitis B infection among pregnant women in the Wa Municipality of Ghana. A cross-sectional study employing systematic random sampling was conducted among 183 consented pregnant women who went for antenatal care in nine health facilities in the Wa Municipality. A structured validated questionnaire was used to collect information about socio-demographic and obstetric characteristics, awareness of Hepatitis B Virus (HBV) transmission and its prevention. Blood samples (3.0 mls) were collected from each participant to test for HBV serum markers using a Wondfo One Step HBV rapid immunochromatographic assay (Catalog number W003) for the Hepatitis B surface antigen (HBsAg). We conducted descriptive statistics including the prevalence and used multivariable logistic regression to determine the risk of Hepatitis B among study participants. Data was analysed using Stata/SE 15. About 20.2% of the 183 pregnant women screened tested positive for HBsAg. Generally, compared with younger pregnant women, older (> = 25) pregnant women were >9 times less likely to test positive for both chronic Hepatitis B core antibody (HBcAb) and (HBeAg) Hepatitis B infections. However, pregnant women in polygamous relationship were more likely to test positive for both (HBcAb) and (HBsAg and HBeAg) Hepatitis B infections compared with those in monogamous relationship. In a multivariable analysis, pregnant women in a polygamous relationships were about 5 times more likely to test positive for HBsAg (AOR = 4.61, 95% CI: 2.06-9.89) and HBcAb (AOR = 4.89, 95% CI:1.52-6.81) and HBeAg (AOR = 4.62, 95% CI:1.21-6.39) compared with those in a monogamous relationship. This study highlights a high HBsAg prevalence among pregnant women with those in polygamous relationship and younger age more likely to test positive. Facility and community-based health services should emphasize the need for regular screening, education, and vaccination of pregnant women, especially those at high risk, to prevent mother-to-child transmission of viral hepatitis B.
Collapse
Affiliation(s)
| | - Simon Aabalekuu
- Department of Public Health, Regional Health Directorate, Upper West Region, Wa, Ghana
| | - Frederick Dun-Dery
- Department of Paediatrics, Cumming School of Medicine, University of Calgary, Alberta, Canada
| | - Elvis Dun-Dery
- Department of Public Health, Purdue University, West Lafayette, IN, United States of America
| | - Fidelis Bayor
- Department of Anaesthesiology, Lawra Municipal Hospital, Ghana Health Service, Wa, Ghana
| | - Martin Nyaaba Adokiya
- Department of Epidemiology and Biostatistics, School of Public Health, University for Development Studies, Tamale, Ghana
| | | |
Collapse
|
24
|
Wondmeneh TG, Mekonnen AT. Epidemiology of hepatitis B virus infection among pregnant women in Africa: a systematic review and meta-analysis. BMC Infect Dis 2024; 24:921. [PMID: 39237884 PMCID: PMC11375975 DOI: 10.1186/s12879-024-09839-3] [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: 06/03/2024] [Accepted: 08/29/2024] [Indexed: 09/07/2024] Open
Abstract
BACKGROUND Although hepatitis B infection is highly endemic in Africa, information on its epidemiology among pregnant women in the region is limited. Therefore, this systematic review provided up-to-date information on the epidemiology of hepatitis B virus (HBsAg) infection among pregnant women in Africa. METHODS A systematic review and meta-analysis was conducted according to the Preferred Reporting Items for Systematic Reviews. The Web of Science, Scopus, PubMed, Google Scholar, and African journals online were searched to identify relevant studies published between January 1, 2015, and May 21, 2024, on hepatitis B virus infection in pregnant women living in Africa. The Joanna Briggs Institute tool was used to assess the methodological qualities of the included studies. The random effects model was used to estimate the pooled prevalence of HBV infection. I2 assessed the amount of heterogeneity. Publication bias was assessed using Egger's test and a funnel plot. RESULTS We included 91 studies from 28 African countries. The pooled prevalence of hepatitis B infection among pregnant women in Africa was 5.89% (95% CI: 5.26-6.51%), with significant heterogeneity between studies (I2 = 97.71%, p < 0.001). Family history of hepatitis B virus infection (AOR = 2.72, 95%CI: 1.53-3.9), multiple sexual partners (AOR = 2.17, 95%CI: 1.3-3.04), and sharing sharp materials were risk factors for hepatitis B infection. CONCLUSION An intermediate endemic level of hepatitis B virus infection (2-7%) was observed among pregnant women in Africa. To prevent disease transmission, interventions should focus on pregnant women with a family history of hepatitis B infection, multiple sexual partners, and sharing sharp materials.
Collapse
Affiliation(s)
| | - Ayal Tsegaye Mekonnen
- Department of Biomedical, College of Medical and Health Science, Samara University, Semera, Ethiopia
| |
Collapse
|
25
|
Wu L, Lai J, Luo Q, Zhang Y, Lin C, Xie D, Chen Y, Deng H, Gao Z, Peng L, Xu W. Long-term hepatitis B surface antigen kinetics after nucleos(t)ide analog discontinuation in patients with noncirrhotic chronic hepatitis B. LIVER RESEARCH 2024; 8:179-187. [PMID: 39957751 PMCID: PMC11771267 DOI: 10.1016/j.livres.2024.07.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/04/2023] [Revised: 03/10/2024] [Accepted: 07/02/2024] [Indexed: 02/18/2025]
Abstract
Background and aim Few studies have reported hepatitis B surface antigen (HBsAg) kinetics after nucleos(t)ide analog (NA) discontinuation in patients with noncirrhotic chronic hepatitis B (CHB). The study specifically investigated long-term HBsAg kinetics after NA discontinuation. Methods Between January 2014 to January 2024, this study prospectively enrolled 106 outpatients with noncirrhotic CHB who met the discontinuation criteria after NA consolidation treatment. Demographic, clinical, and laboratory data were collected and analyzed after NA discontinuation. Results Ninety-six patients who finished 5 years of follow-up were included. HBsAg remained undetectable in 29 patients with end of treatment (EOT) HBsAg negativity. Among 67 patients with EOT HBsAg positivity, HBsAg seroclearance occurred in 12 (17.9%) patients with an estimated annual incidence of HBsAg seroclearance of 3.6%. Patients with EOT HBsAg levels of ≤1000 IU/mL had a higher HBsAg seroclearance rate than those with EOT HBsAg levels of >1000 IU/mL (33.3% vs. 5.4%). The proportion of patients with HBsAg ≤1000 IU/mL increased during follow-up. Logistic regression analysis indicated that the EOT HBsAg level was an independent factor for HBsAg seroclearance and an HBsAg level decline exceeding 1 log10 IU/mL. The optimal EOT HBsAg cutoff for both HBsAg seroclearance and an HBsAg level decline exceeding 1 log10 IU/mL was 359 IU/mL. Conclusions Patients with EOT HBsAg negativity experienced no relapse and maintained HBsAg seroclearance during 5 years of follow-up after NA discontinuation. A higher HBsAg seroclearance rate can be obtained in patients with EOT HBsAg levels of ≤1000 IU/mL during 5 years of follow-up after NA discontinuation. Close monitoring and proper NA retreatment are recommended to guarantee the safety of NA discontinuation. Clinical trial number Clinicaltrials.gov number NCT02883647.
Collapse
Affiliation(s)
- Lina Wu
- Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
- Guangdong Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Jiadi Lai
- Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
- Guangdong Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Qiumin Luo
- Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
- Guangdong Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Yeqiong Zhang
- Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
- Guangdong Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Chaoshuang Lin
- Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
- Guangdong Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Dongying Xie
- Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
- Guangdong Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Youming Chen
- Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
- Guangdong Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Hong Deng
- Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
- Guangdong Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Zhiliang Gao
- Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
- Guangdong Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
- Key Laboratory of Tropical Disease Control, Ministry of Education, Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Liang Peng
- Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
- Guangdong Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
- Key Laboratory of Tropical Disease Control, Ministry of Education, Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Wenxiong Xu
- Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
- Guangdong Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
| |
Collapse
|
26
|
Daniels J, Nartey YA, Djankpa F, Simpore J, Obiri-Yeboah D. Characteristics and antiviral treatment eligibility of patients diagnosed with hepatitis B at a teaching hospital in Ghana: Implications for prevention and management. PLoS One 2024; 19:e0302086. [PMID: 39172867 PMCID: PMC11340950 DOI: 10.1371/journal.pone.0302086] [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: 03/26/2024] [Accepted: 08/07/2024] [Indexed: 08/24/2024] Open
Abstract
Hepatitis B virus (HBV) infection poses a considerable public health challenge in limited-resource settings especially in the sub-Saharan African region. Even though HBV infection is incurable, timely treatment is effective in preventing disease progression to liver cirrhosis or hepatocellular carcinoma. However, not all infected patients require treatment. The aim of the study was to determine the clinical, immunological, and virological profiles of treatment naïve patients with HBV infection, seen at the outpatient clinic of the Cape Coast Teaching Hospital. Additionally, the study sought to determine the antiviral treatment eligibility rate based on the 2015 guidelines of the World Health Organization (WHO) compared with the new 2024 guidelines. A hospital-based cross-sectional study involving total sampling of 220 treatment naïve HBV surface antigen positive clients was carried out. A structured questionnaire was used to collect data that were analyzed with STATA version 16. The median age at diagnosis was 34 years (IQR 26.0-41.5) with a male to female ratio of 1:1.5. A total of 138 participants (62.7%) were diagnosed with HBV infection following voluntary testing. There was a median delay of 8.5 months (IQR 3.0-22.5) between initial diagnosis and patients' presentation for medical care. In all, 24 patients (10.9%) had abnormal clinical examination findings, 172 patients (78.2%) had HBV DNA levels ≤ 2000 IU/ml whereas 8 (3.6%) were seropositive for the HBV envelope antigen. A few patients had concomitant human immunodeficiency virus (2.7%) and hepatitis C virus (1.4%) infections. Treatment eligibility rate based on the WHO 2015 guidelines was 6.4% (n = 14), however, with the updated 2024 guidelines, treatment eligibility was 42.3% (n = 93). Increasing the screening rate among the general population, early linkage to clinical care of screen positives and vaccination of screen negatives will help reduce HBV-related clinical conditions in resource-limited settings.
Collapse
Affiliation(s)
- Joseph Daniels
- National Centre for Radiotherapy, Oncology and Nuclear Medicine, Korle Bu Teaching Hospital, Accra, Ghana
- Department of Microbiology and Immunology, School of Medical Sciences, University of Cape Coast, Cape Coast, Ghana
| | - Yvonne A. Nartey
- Department of Internal Medicine and Therapeutics, School of Medical Sciences, University of Cape Coast, Cape Coast, Ghana
| | - Francis Djankpa
- Department of Physiology, School of Medical Sciences, University of Cape Coast, Cape Coast, Ghana
| | - Jacques Simpore
- Centre de Recherche Biomoléculaire Pietro Annigoni (CERBA), Ouagadougou, Burkina Faso
| | - Dorcas Obiri-Yeboah
- Department of Microbiology and Immunology, School of Medical Sciences, University of Cape Coast, Cape Coast, Ghana
| |
Collapse
|
27
|
Jiao L, Shen T, Han Y, Liu W, Liu W, Dang L, Wei M, Yang Y, Guo J, Miao M, Xu X. The spatial-temporal distribution of hepatitis B virus infection in China,2006-2018. BMC Infect Dis 2024; 24:811. [PMID: 39129008 PMCID: PMC11318140 DOI: 10.1186/s12879-024-09716-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: 06/28/2023] [Accepted: 08/05/2024] [Indexed: 08/13/2024] Open
Abstract
OBJECTIVES Hepatitis B is a liver disease caused by Hepatitis B virus (HBV) infection and is highly prevalent in China. To better understand the epidemiological characteristics of hepatitis B in China and develop effective disease control strategies, we employed temporal and spatial statistical methods. METHODS We obtained HBV incidence data from the Public Health Science Data Center of the Chinese Center for Disease Control and Prevention for the years 2006 to 2018. Using Geographic Information System (GIS) and SaTScan scanning technology, we conducted spatial autocorrelation analysis and spatiotemporal scan analysis to create a map and visualize the distribution of hepatitis B incidence. RESULTS While hepatitis B incidence rebounded in 2011 and 2017, the overall incidence in China decreased.In the trend analysis by item, the incidence varies from high to low. The global spatial autocorrelation analysis revealed a clustered distribution, and the Moran index analysis of spatial autocorrelation within local regions identified five provinces as H-H clusters (hot spots), while one province was an L-L cluster (cold spot). Spatial scan analysis identified 11 significant spatial clusters. CONCLUSIONS We found significant clustering in the spatial distribution of hepatitis B incidence and positive spatial correlation of hepatitis B incidence in China. We also identified high-risk times and regional clusters of hepatitis B incidence.
Collapse
Affiliation(s)
- Liping Jiao
- Laboratory Department, Weinan Center for Disease Control and Prevention, Weinan, Shaanxi, China
| | - Tuo Shen
- Laboratory Department, Weinan Center for Disease Control and Prevention, Weinan, Shaanxi, China.
| | - Yingzi Han
- Laboratory Department, Weinan Center for Disease Control and Prevention, Weinan, Shaanxi, China
| | - Wen Liu
- Department of Biological Sciences, University of Alberta, Edmonton, Alberta, Canada
| | - Wei Liu
- Laboratory Department, Weinan Center for Disease Control and Prevention, Weinan, Shaanxi, China
| | - Lin Dang
- Laboratory Department, Weinan Center for Disease Control and Prevention, Weinan, Shaanxi, China
| | - Mingmin Wei
- Laboratory Department, Weinan Center for Disease Control and Prevention, Weinan, Shaanxi, China
| | - Yunyun Yang
- Laboratory Department, Weinan Center for Disease Control and Prevention, Weinan, Shaanxi, China
| | - Jingjing Guo
- Laboratory Department, Weinan Center for Disease Control and Prevention, Weinan, Shaanxi, China
| | - Meirong Miao
- Laboratory Department, Weinan Center for Disease Control and Prevention, Weinan, Shaanxi, China
| | - Xiangming Xu
- Laboratory Department, Weinan Center for Disease Control and Prevention, Weinan, Shaanxi, China
| |
Collapse
|
28
|
Ayinde M, Olufemi-Aworinde K, Joel-Medewase V, Aliu-Ayinde M, Aworinde O, Adeyemi A. Determinants of mother-to-child transmission of hepatitis B virus among pregnant women in southwestern Nigeria. Pan Afr Med J 2024; 48:161. [PMID: 39629313 PMCID: PMC11613995 DOI: 10.11604/pamj.2024.48.161.41605] [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: 09/02/2023] [Accepted: 06/28/2024] [Indexed: 12/07/2024] Open
Abstract
Introduction hepatitis B virus (HBV) infection is a serious public health problem in sub-Saharan Africa and a common cause of liver disease globally. This study aimed to determine the seroprevalence and the rate of mother-to-child transmission of HBV after the age of viability. Methods the study was a cross-sectional study that involved 543 eligible consenting pregnant women and newborns of Hepatitis B surface antigen (HBsAg) positive mothers. A one-step rapid HBsAg strip was used to screen eligible patients for HBV infection. Venous blood sample (5mls) was taken from every HBsAg-positive woman for Hepatitis B e Antigen (HBeAg), Hepatitis B e antibody (HBeAb), Hepatitis B core Antibody (HBcAb) and Hepatitis B surface Antibody (HBsAb). In addition, 2mls of cord blood was taken to assay for HBsAg and HBV DNA. Data was analysed using SPSS version 22. Results of 543 pregnant women screened, 18 (3.3%) of them were HBsAg-positive with all of them testing negative for HBeAg. HBV DNA was detected in the cord blood of 4 (22.2%) new-borns delivered while 2 (11.1%) tested positive for HBsAg; the above finding indicated that only 4 of the neonates had detectable HBV DNA (>100copies/ml) in their cord blood. Conclusion findings from this study demonstrate a low prevalence of HBV infection among pregnant women after the age of viability in Ogbomoso. HBV DNA analysis rather than HBsAg was shown to be more sensitive and specific in determining the risk of intrauterine infections.
Collapse
Affiliation(s)
- Musa Ayinde
- Department of Obstetrics and Gynaecology, Faculty of Clinical Sciences, Ladoke Akintola University of Technology, Ogbomoso, Nigeria
| | - Kehinde Olufemi-Aworinde
- Department of Haematology and Blood Transfusion, Faculty of Basic Clinical Sciences, Ladoke Akintola University of Technology, Ogbomoso, Nigeria
| | - Victor Joel-Medewase
- Department of Paediatrics and Child Health, Faculty of Clinical Sciences, Ladoke Akintola University of Technology, Ogbomoso, Nigeria
| | - Medinat Aliu-Ayinde
- Department of Epidemiology and Community Health, Faculty of Clinical Sciences, University of Ilorin, Ilorin, Nigeria
| | - Olufemi Aworinde
- Department of Obstetrics and Gynaecology, Faculty of Clinical Sciences, Ladoke Akintola University of Technology, Ogbomoso, Nigeria
| | - Adewale Adeyemi
- Department of Obstetrics and Gynaecology, Faculty of Clinical Sciences, Ladoke Akintola University of Technology, Ogbomoso, Nigeria
| |
Collapse
|
29
|
Atanaw T, Girmay G, Zemene A, Assefa M, Eshetie T, Bewket G, Alemiye F, Belete D, Birhane N. Seroprevalence of hepatitis B and C viruses and some possible associated factors among cancer patients at the Oncology Treatment Center, Gondar, Northwest Ethiopia: A cross-sectional study. PLoS One 2024; 19:e0308161. [PMID: 39093829 PMCID: PMC11296633 DOI: 10.1371/journal.pone.0308161] [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: 03/28/2024] [Accepted: 07/17/2024] [Indexed: 08/04/2024] Open
Abstract
BACKGROUND Cancer patients are prone to infections such as hepatitis B virus (HBV) and hepatitis C virus (HCV), which pose a major public health challenge, especially in developing countries. However, little is known about the magnitude of these infections among cancer patients in Ethiopia. Thus, this study determined the prevalence of HBV and HCV in cancer patients at the Oncology Treatment Center, Gondar, Northwest Ethiopia. MATERIALS AND METHODS An institutional-based cross-sectional study was conducted on 115 cancer patients from 15 April to 22 July 2023 at the Oncology Treatment Center, Gondar, Northwest Ethiopia. Sociodemographic, clinical, and other relevant data were collected using a pretested structured questionnaire. Five milliliters of venous blood were collected using a vacutainer tube, serum was harvested and tested for HBV and HCV using a one-step HBsAg and anti-HCV test strip with further confirmation through an ELISA test kit. Data were analyzed using SPSS version 20 and Fisher exact test was used to determine the association between HBV/HCV infection and associated factors. RESULTS Out of 115 cancer patients, the majority (62.6%) were females. The median age was 50 (IQR; 40-56) years. The overall prevalence of HBV and HCV infections was 4.3% (95% CI; 0.6-8%) and 6.1% (95% CI; 1.7-10.5%), respectively. Sex was significantly associated with the prevalence of HCV (p = 0.011) with higher anti-HCV positivity in males (14%) than in females (1.4%). CONCLUSIONS In this study, the prevalence of HCV was higher and the HBV prevalence was intermediate in cancer patients. To reduce the burden of HBV and HCV infections, it is crucial to provide access to HBV and HCV screening services, strengthen vaccination, and improve prompt treatment in cancer patients.
Collapse
Affiliation(s)
- Tadesse Atanaw
- University of Gondar Comprehensive Specialized Hospital, Gondar, Ethiopia
| | - Getu Girmay
- Department of Immunology and Molecular Biology, School of Biomedical and Laboratory Science, College of Medicine and Health Sciences, University of Gondar, Gondar, Ethiopia
| | - Aragaw Zemene
- Department of Medical Biotechnology, Institute of Biotechnology, University of Gondar, Gondar, Ethiopia
| | - Muluneh Assefa
- Department of Medical Microbiology, School of Biomedical and Laboratory Science, College of Medicine and Health Sciences, University of Gondar, Gondar, Ethiopia
| | - Tewodros Eshetie
- Department of Medical Biotechnology, Institute of Biotechnology, University of Gondar, Gondar, Ethiopia
| | - Gezahegn Bewket
- Department of Immunology and Molecular Biology, School of Biomedical and Laboratory Science, College of Medicine and Health Sciences, University of Gondar, Gondar, Ethiopia
| | - Fikadu Alemiye
- Department of Internal Medicine, School of Medicine, College of Medicine and Health Sciences, University of Gondar, Gondar, Ethiopia
| | - Debaka Belete
- Department of Medical Microbiology, School of Biomedical and Laboratory Science, College of Medicine and Health Sciences, University of Gondar, Gondar, Ethiopia
| | - Nega Birhane
- Department of Medical Biotechnology, Institute of Biotechnology, University of Gondar, Gondar, Ethiopia
| |
Collapse
|
30
|
Ding Y, Guo H, Hong X, Li Q, Miao Z, Pan Q, Zheng K, Wang W. The distinct spatiotemporal evolutionary landscape of HBV and HDV largely determines the unique epidemic features of HDV globally. Mol Phylogenet Evol 2024; 197:108114. [PMID: 38825156 DOI: 10.1016/j.ympev.2024.108114] [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: 08/21/2023] [Revised: 05/07/2024] [Accepted: 05/26/2024] [Indexed: 06/04/2024]
Abstract
Chronic infection of hepatitis B virus (HBV) and hepatitis D virus (HDV) causes the most severe form of viral hepatitis. Due to the dependence on HBV, HDV was deemed to co-evolve and co-migrate with HBV. However, we previously found that the naturally occurred HDV/HBV combinations do not always reflect the most efficient virological adaptation (Wang et al., 2021). Moreover, regions with heavy HBV burden do not always correlate with high HDV prevalence (e.g., East Asia), and vice versa (e.g., Central Asia). Herein, we systematically elucidated the spatiotemporal evolutionary landscape of HDV to understand the unique epidemic features of HDV. We found that the MRCA of HDV was from South America around the late 13th century, was globally dispersed mainly via Central Asia, and evolved into eight genotypes from the 19th to 20th century. In contrast, the MRCA of HBV was from Europe ∼23.7 thousand years ago (Kya), globally dispersed mainly via Africa and East Asia, and evolved into eight genotypes ∼1100 years ago. When HDV stepped in, all present-day HBV genotypes had already formed and its global genotypic distribution had stayed stable geographically. Nevertheless, regionalized HDV adapted to local HBV genotypes and human lineages, contributing to the global geographical separation of HDV genotypes. Additionally, a sharp increase in HDV infections was observed after the 20th century. In conclusion, HDV exhibited a distinct spatiotemporal distribution path compared with HBV. This unique evolutionary relationship largely fostered the unique epidemic features we observe nowadays. Moreover, HDV infections may continue to ramp up globally, thus more efforts are urgently needed to combat this disease.
Collapse
Affiliation(s)
- Yibo Ding
- Department of Pathogen Biology and Immunology, Jiangsu Key Laboratory of Immunity and Metabolism, Jiangsu International Laboratory of Immunity and Metabolism, Xuzhou Medical University, Xuzhou, China
| | - Hongbo Guo
- Department of Pathogen Biology and Immunology, Jiangsu Key Laboratory of Immunity and Metabolism, Jiangsu International Laboratory of Immunity and Metabolism, Xuzhou Medical University, Xuzhou, China.
| | - Xinfang Hong
- Second Medical Center of PLA General Hospital, Beijing, China
| | - Qiudi Li
- Department of Pathogen Biology and Immunology, Jiangsu Key Laboratory of Immunity and Metabolism, Jiangsu International Laboratory of Immunity and Metabolism, Xuzhou Medical University, Xuzhou, China
| | - Zhijiang Miao
- Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming, China
| | - Qiuwei Pan
- Department of Gastroenterology and Hepatology, Erasmus MC-University Medical Center, Rotterdam, The Netherlands.
| | - Kuiyang Zheng
- Department of Pathogen Biology and Immunology, Jiangsu Key Laboratory of Immunity and Metabolism, Jiangsu International Laboratory of Immunity and Metabolism, Xuzhou Medical University, Xuzhou, China.
| | - Wenshi Wang
- Department of Pathogen Biology and Immunology, Jiangsu Key Laboratory of Immunity and Metabolism, Jiangsu International Laboratory of Immunity and Metabolism, Xuzhou Medical University, Xuzhou, China.
| |
Collapse
|
31
|
Sun W, Nan J, Xu H, Wang L, Niu J, Zhang J, Yang B. Neural Network Enables High Accuracy for Hepatitis B Surface Antigen Detection with a Plasmonic Platform. NANO LETTERS 2024; 24:8784-8792. [PMID: 38975746 DOI: 10.1021/acs.nanolett.4c02860] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 07/09/2024]
Abstract
The detection of hepatitis B surface antigen (HBsAg) is critical in diagnosing hepatitis B virus (HBV) infection. However, existing clinical detection technologies inevitably cause certain inaccuracies, leading to delayed or unwarranted treatment. Here, we introduce a label-free plasmonic biosensing method based on the thickness-sensitive plasmonic coupling, combined with supervised deep learning (DL) using neural networks. The strategy of utilizing neural networks to process output data can reduce the limit of detection (LOD) of the sensor and significantly improve the accuracy (from 93.1%-97.4% to 99%-99.6%). Compared with widely used emerging clinical technologies, our platform achieves accurate decisions with higher sensitivity in a short assay time (∼30 min). The integration of DL models considerably simplifies the readout procedure, resulting in a substantial decrease in processing time. Our findings offer a promising avenue for developing high-precision molecular detection tools for point-of-care (POC) applications.
Collapse
Affiliation(s)
- Weihong Sun
- Joint Laboratory of Opto-Functional Theranostics in Medicine and Chemistry, The First Hospital of Jilin University, Changchun 130021, P. R. China
- State Key Laboratory of Supramolecular Structure and Materials, Center for Supramolecular Chemical Biology, College of Chemistry, Jilin University, Changchun 130012, P. R. China
| | - Jingjie Nan
- Joint Laboratory of Opto-Functional Theranostics in Medicine and Chemistry, The First Hospital of Jilin University, Changchun 130021, P. R. China
- State Key Laboratory of Supramolecular Structure and Materials, Center for Supramolecular Chemical Biology, College of Chemistry, Jilin University, Changchun 130012, P. R. China
| | - Hongqin Xu
- Department of Hepatology, Center of Infectious Diseases and Pathogen Biology, The First Hospital of Jilin University, Changchun 130021, P. R. China
| | - Lei Wang
- Joint Laboratory of Opto-Functional Theranostics in Medicine and Chemistry, The First Hospital of Jilin University, Changchun 130021, P. R. China
- State Key Laboratory of Supramolecular Structure and Materials, Center for Supramolecular Chemical Biology, College of Chemistry, Jilin University, Changchun 130012, P. R. China
| | - Junqi Niu
- Department of Hepatology, Center of Infectious Diseases and Pathogen Biology, The First Hospital of Jilin University, Changchun 130021, P. R. China
| | - Junhu Zhang
- Joint Laboratory of Opto-Functional Theranostics in Medicine and Chemistry, The First Hospital of Jilin University, Changchun 130021, P. R. China
- State Key Laboratory of Supramolecular Structure and Materials, Center for Supramolecular Chemical Biology, College of Chemistry, Jilin University, Changchun 130012, P. R. China
| | - Bai Yang
- Joint Laboratory of Opto-Functional Theranostics in Medicine and Chemistry, The First Hospital of Jilin University, Changchun 130021, P. R. China
- State Key Laboratory of Supramolecular Structure and Materials, Center for Supramolecular Chemical Biology, College of Chemistry, Jilin University, Changchun 130012, P. R. China
| |
Collapse
|
32
|
Jeong Y, Han J, Jang KL. Reactive Oxygen Species Induction by Hepatitis B Virus: Implications for Viral Replication in p53-Positive Human Hepatoma Cells. Int J Mol Sci 2024; 25:6606. [PMID: 38928309 PMCID: PMC11204012 DOI: 10.3390/ijms25126606] [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: 04/24/2024] [Revised: 06/03/2024] [Accepted: 06/11/2024] [Indexed: 06/28/2024] Open
Abstract
Hepatitis B virus (HBV) infects approximately 300 million people worldwide, causing chronic infections. The HBV X protein (HBx) is crucial for viral replication and induces reactive oxygen species (ROS), leading to cellular damage. This study explores the relationship between HBx-induced ROS, p53 activation, and HBV replication. Using HepG2 and Hep3B cell lines that express the HBV receptor NTCP, we compared ROS generation and HBV replication relative to p53 status. Results indicated that HBV infection significantly increased ROS levels in p53-positive HepG2-NTCP cells compared to p53-deficient Hep3B-NTCP cells. Knockdown of p53 reduced ROS levels and enhanced HBV replication in HepG2-NTCP cells, whereas p53 overexpression increased ROS and inhibited HBV replication in Hep3B-NTCP cells. The ROS scavenger N-acetyl-L-cysteine (NAC) reversed these effects. The study also found that ROS-induced degradation of the HBx is mediated by the E3 ligase Siah-1, which is activated by p53. Mutations in p53 or inhibition of its transcriptional activity prevented ROS-mediated HBx degradation and HBV inhibition. These findings reveal a p53-dependent negative feedback loop where HBx-induced ROS increases p53 levels, leading to Siah-1-mediated HBx degradation and HBV replication inhibition. This study offers insights into the molecular mechanisms of HBV replication and identifies potential therapeutic targets involving ROS and p53 pathways.
Collapse
Affiliation(s)
- Yuna Jeong
- Department of Integrated Biological Science, The Graduate School, Pusan National University, Busan 46241, Republic of Korea; (Y.J.); (J.H.)
| | - Jiwoo Han
- Department of Integrated Biological Science, The Graduate School, Pusan National University, Busan 46241, Republic of Korea; (Y.J.); (J.H.)
| | - Kyung Lib Jang
- Department of Integrated Biological Science, The Graduate School, Pusan National University, Busan 46241, Republic of Korea; (Y.J.); (J.H.)
- Department of Microbiology, College of Natural Science, Pusan National University, Busan 46241, Republic of Korea
- Microbiological Resource Research Institute, Pusan National University, Busan 46241, Republic of Korea
| |
Collapse
|
33
|
Duracinsky M, Yaya I, Yombo-Kokule L, Bessonneau P, Thonon F, Rousset-Torrente O, Roudot-Thoraval F, Lert F, Zucman D, Chassany O. Development of a risk prediction score for screening for HBV, HCV and HIV among migrants in France: results from a multicentre observational study (STRADA study). BMJ Open 2024; 14:e075315. [PMID: 38839381 PMCID: PMC11163614 DOI: 10.1136/bmjopen-2023-075315] [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: 05/04/2023] [Accepted: 12/14/2023] [Indexed: 06/07/2024] Open
Abstract
OBJECTIVES Migrants from high HIV, hepatitis B virus (HBV) or hepatitis C virus (HCV) endemicity regions have a great burden of these infections and related diseases in the host countries. This study aimed to assess the predictive capacity of the Test Rapide d'Orientation Diagnostique (TROD) Screen questionnaire for HIV, HBV and HCV infections among migrants arriving in France. DESIGN An observational and multicentre study was conducted among migrants. A self-questionnaire on demographic characteristics, personal medical history and sexual behaviours was completed. SETTING The study was conducted in the centres of the French Office for Immigration and Integration (OFII). PARTICIPANTS Convenience sampling was used to select and recruit adult migrants between January 2017 and March 2020. OUTCOME MEASURES Participants were tested for HIV, HBV and HCV with rapid tests. For each infection, the test performance was assessed using receiver operating characteristics curves, using area under the curve (AUC) as a measure of accuracy. RESULTS Among 21 133 regular migrants seen in OFII centres, 15 343 were included in the study. The participants' mean age was 35.6 years (SD±11.1). The prevalence (95% CI) of HBV, HCV and HIV was 2.0% (1.8% to 2.2%), 0.3% (0.2% to 0.4%) and 0.3% (0.2% to 0.4%), respectively. Based on the sensitivity-specificity curve analysis, the cut-off points (95% CI) chosen for the risk score were: 2.5 (2.5 to 7.5) for HBV infection in men; 6.5 (0.5 to 6.5) for HBV infection in women; 9.5 (9.5 to 12.5) for HCV infection; and 10.5 (10.0 to 18.5) for HIV infection. Test performance was highest for HIV (AUC=82.15% (95% CI 74.54% to 87.99%)), followed by that for HBV in men (AUC=79.22%, (95% CI 76.18% to 82.26%)), for HBV in women (AUC=78.83 (95% CI 74.54% to 82.10%)) and that for HCV (AUC=75.95% (95% CI 68.58% to 83.32%)). CONCLUSION The TROD screen questionnaire showed good overall performance for predicting HIV, HBV and HCV infections among migrants in OFII centres. It could be used to optimise screening for these infections and to propose rapid screening tests to those who are at high risk. TRIAL REGISTRATION NUMBER NCT02959684.
Collapse
Affiliation(s)
- Martin Duracinsky
- Patient-Reported Outcomes Research (PROQOL), Health Economics Clinical Trial Unit (URC-ECO), Hotel-Dieu Hospital, AP- HP, Paris, France
- ECEVE, UMR-S 1123, Paris Cité University, Inserm, Paris, France
- Internal Medicine Unit, Le Kremlin Bicêtre Hospital, Bicêtre, France
| | - Issifou Yaya
- Patient-Reported Outcomes Research (PROQOL), Health Economics Clinical Trial Unit (URC-ECO), Hotel-Dieu Hospital, AP- HP, Paris, France
- ECEVE, UMR-S 1123, Paris Cité University, Inserm, Paris, France
| | - Lisa Yombo-Kokule
- Patient-Reported Outcomes Research (PROQOL), Health Economics Clinical Trial Unit (URC-ECO), Hotel-Dieu Hospital, AP- HP, Paris, France
- ECEVE, UMR-S 1123, Paris Cité University, Inserm, Paris, France
| | - Pascal Bessonneau
- Patient-Reported Outcomes Research (PROQOL), Health Economics Clinical Trial Unit (URC-ECO), Hotel-Dieu Hospital, AP- HP, Paris, France
- ECEVE, UMR-S 1123, Paris Cité University, Inserm, Paris, France
| | - Frédérique Thonon
- Patient-Reported Outcomes Research (PROQOL), Health Economics Clinical Trial Unit (URC-ECO), Hotel-Dieu Hospital, AP- HP, Paris, France
- ECEVE, UMR-S 1123, Paris Cité University, Inserm, Paris, France
| | - Olivia Rousset-Torrente
- Patient-Reported Outcomes Research (PROQOL), Health Economics Clinical Trial Unit (URC-ECO), Hotel-Dieu Hospital, AP- HP, Paris, France
- ECEVE, UMR-S 1123, Paris Cité University, Inserm, Paris, France
| | | | - France Lert
- Paris Fast Track City Initiative (FTCI) program, Paris, France
| | - David Zucman
- Department of Internal Medicine, Foch Hospital, Suresnes, France
| | - Olivier Chassany
- Patient-Reported Outcomes Research (PROQOL), Health Economics Clinical Trial Unit (URC-ECO), Hotel-Dieu Hospital, AP- HP, Paris, France
- ECEVE, UMR-S 1123, Paris Cité University, Inserm, Paris, France
| |
Collapse
|
34
|
Chen PJ. Challenges for hepatitis B control in Asia-Pacific areas: Consolidating vaccination and rolling-out antiviral therapies. J Gastroenterol Hepatol 2024; 39:1033-1039. [PMID: 38413195 DOI: 10.1111/jgh.16528] [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: 01/28/2024] [Accepted: 02/07/2024] [Indexed: 02/29/2024]
Abstract
Chronic hepatitis B (CHB) was, and still is, a prevalent liver disease in the world, especially high in the Asia-Pacific areas. With the advent of preventive vaccines and effective viral suppression drugs and active implementations, CHB has gradually become under control. The world-wide prevalence reduces from 4.2% in 1980 to 3.2% in 2020 study. CHB patients receiving long-term antiviral therapies significantly improve the clinical outcomes, saving from end-stage liver diseases. Despite of these impressive progresses, to meet the WHO sustained development goals (SDG) for CHB control, a 90% reduction of incidence and a 65% reduction of mortality in year 2030, there is still a long way to go. In this review, four ongoing approaches have been proposed: (i) A continuous monitoring of long-term vaccine efficacy in vaccinated populations; (ii) consolidating the hepatitis B virus vaccination program against vaccine hesitancy and limited resources; (iii) rolling-out current oral antivirals to more CHB patients not only for diseases treatment but also for infection preventions; and (iv) development of curative therapies, both friendly-to-dispense and affordable. A coherent and persevere efforts by the society may succeed and achieve the SDG for CHB in the future.
Collapse
Affiliation(s)
- Pei-Jer Chen
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- National Taiwan University College of Medicine, Taipei, Taiwan
| |
Collapse
|
35
|
Senoo-Dogbey VE, Ohene LA, Wuaku DA. Occupational exposure to Hepatitis B virus, disease burden and pathways for postexposure prophylaxis management: recommendations for healthcare workers in highly endemic settings. Infect Prev Pract 2024; 6:100354. [PMID: 38559369 PMCID: PMC10979087 DOI: 10.1016/j.infpip.2024.100354] [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: 10/07/2023] [Accepted: 02/28/2024] [Indexed: 04/04/2024] Open
Abstract
Hepatitis B Virus (HBV) was recognized many decades ago as an important occupational hazard for Health Care Workers (HCWs) globally. HCWs who are directly involved in patient care and are in continuous contact with blood or body fluids have an increased risk of occupationally acquiring the virus. The risk of HCWs in highly endemic areas is greater due to the greater prevalence of infection in the general population. Recommendations are available to guide HBV prevention activities or practices among HCWs. These include the use of the hepatitis B vaccine as a preexposure prophylaxis and the use of hepatitis B immunoglobulin alone or hepatitis B immunoglobulin plus the vaccine as postexposure prophylaxis. The uptake of preexposure prophylaxis has been observed to be low in resource-poor settings where the disease is highly endemic. Postexposure prophylaxis has become the remedy for preventing occupational transmission of HBV in these settings. This review aimed to summarize the available evidence on the risk of transmission of HBV infection, the burden of infection and recommendations for pre- and postexposure prophylaxis for the prevention of occupational acquisition of HBV among HCWs. We conducted a narrative review to summarize the evidence available on the recommended steps of HBV exposure management and the utilization of post-exposure prophylaxis (PEP) for HBV. A comprehensive search was conducted in PubMed, Science Direct, Google Scholar, and Africa Journals Online (AJOL) databases. The keywords used were hepatitis B, hepatitis B virus postexposure prophylaxis, occupational exposures, and recommendations for postexposure to hepatitis B virus. We gleaned evidence from the literature sources and summarized the concepts related to exposure forms, postexposure prophylaxis management pathways and recommendations for the utilization of postexposure prophylaxis among exposed healthcare workers. From the synthesis of evidence, we conclude that HBV infection is a life-threatening condition. However, the disease is preventable by using the HBV vaccine as a preexposure prophylaxis measure. An effective postexposure prophylaxis management program is also available, and the last resort to preventing occupational transmission of HBV among HCWs who non-responders are, or who fail to vaccinate completely against HBV. Irrespective of the availability of these lifesaving interventions, the use of pre- and post-exposure prophylaxis among HCWs in highly endemic regions is suboptimal. Many barriers operating at the individual HCW and health facility levels have been identified as impacting the successful use of HBV preventive measures.
Collapse
Affiliation(s)
- Vivian Efua Senoo-Dogbey
- Department of Public Health, School of Nursing and Midwifery, University of Ghana, P. O. Box LG 25, Legon, Accra, Ghana
- Ghana Institute of Management and Public Administration, Ghana
| | - Lillian Akorfa Ohene
- Department of Public Health, School of Nursing and Midwifery, University of Ghana, P. O. Box LG 25, Legon, Accra, Ghana
| | - Delali Adwoa Wuaku
- Department of Nursing Research, Nursing, and Midwifery Training School, Korle-Bu, P. O Box KB 83, Accra, Ghana
| |
Collapse
|
36
|
Maung ST, Deepan N, Decharatanachart P, Chaiteerakij R. Screening for viral hepatitis B infection in cancer patients before receiving chemotherapy - A systematic review and meta-analysis. Asia Pac J Clin Oncol 2024; 20:335-345. [PMID: 38512893 DOI: 10.1111/ajco.14055] [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: 12/29/2023] [Revised: 02/08/2024] [Accepted: 03/03/2024] [Indexed: 03/23/2024]
Abstract
AIM We conducted a systematic review and meta-analysis to assess the hepatitis B virus (HBV) screening rate in cancer patients before systemic chemotherapy, aiming to identify those needing antiviral prophylaxis for HBV reactivation. METHODS We searched PubMed, Embase, Scopus, and Google Scholar for relevant studies. The pooled screening rate was estimated using a random effects model. Subgroup analyses were conducted based on malignancy types, chemotherapy regimens, study period, and HBV endemic regions. RESULTS The meta-analysis included 29 studies from various endemic regions (19 low-endemic, three lower intermediate-endemic, and seven higher intermediate-endemic). These studies encompassed hematologic malignancies (n = 10), solid-organ tumors (n = 4), and combinations (n = 15). Seven studies used rituximab-containing regimens, four did not, and the remaining 11 did not specify chemotherapy regimens. The pooled screening rate was 57% (95% confidence interval [95%CI]: 46%-68%, I2 = 100%). Over time, screening rates improved from 37% (95%CI: 23%-53%) in 2006-2010 to 68% (54%-80%) in 2011-2015 and 69% (48%-84%) in 2016-2020. Screening rates were highest at 89% (74%-96%) in high endemic countries, followed by 60% (45-73%) in lower-intermediate and 49% (34-64%) in low-endemic countries. Patients with hematological malignancies had a higher screening rate than those with solid organ tumors, 65% (55%-74%) versus 37% (21%-57%), respectively. A screening rate was higher in patients receiving rituximab-containing chemotherapy than non-rituximab regimens, 68% (55%-79%) versus 45% (27%-65%). CONCLUSION Despite existing guidelines, pre-chemotherapy HBV screening rate remains unsatisfactory, with substantial heterogeneous rates globally. These findings underscore the need for effective strategies to align practices with clinical guidelines.
Collapse
Affiliation(s)
- Soe Thiha Maung
- Division of Gastroenterology, Department of Internal Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand
- Ma Har Myaing Hospital, Yangon, Myanmar
| | - Natee Deepan
- Division of Academic Affairs, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | | | - Roongruedee Chaiteerakij
- Division of Gastroenterology, Department of Internal Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand
- Center of Excellence for Innovation and Endoscopy in Gastrointestinal Oncology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| |
Collapse
|
37
|
Jalal MA, Karami M, Namdari M, Lami F, Taher TMJ, Etemad K. Identifying Expert Opinions on the Challenges and Barriers Faced in Implementing Iraq's National Plan for Controlling Hepatitis B. Cureus 2024; 16:e62814. [PMID: 39036276 PMCID: PMC11260289 DOI: 10.7759/cureus.62814] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/20/2024] [Indexed: 07/23/2024] Open
Abstract
BACKGROUND This study examined the difficulties and obstacles faced by healthcare professionals in implementing Iraq's national plan for hepatitis B virus (HBV) control. This research aims to offer valuable insights into the intricacies of HBV control efforts and identify key areas for improvement. METHODS In this qualitative study, semi-structured interviews were conducted with a purposive sample of 10 physicians, representing diverse medical specialties and healthcare settings, including experts in the fields of medical sciences. Data analysis was conducted using MAXQDA software, version 24 (VERBI Software GmbH, Berlin, Germany) to identify recurring themes and gain insights into the challenges encountered during the implementation of the national plan. RESULTS Ten physicians participated in the study, providing insights into challenges and barriers hindering the effective implementation of Iraq's national plan for HBV control. Consensus among participants highlighted challenges such as resource constraints, inadequate infrastructure, population ignorance, and vaccine refusal. Documentation challenges, including inaccuracies in reporting HBV-associated mortality, were also noted. Barriers to successful implementation included poor public awareness, inadequate education for healthcare providers, and funding shortages. Unmet needs highlighted the necessity for unified protocols, surveillance systems, and international training programs. The improvement strategies proposed by participants emphasized raising awareness, supporting primary healthcare centers, and enhancing funding allocation. CONCLUSION This study underscores significant challenges in implementing Iraq's national plan for HBV control, with barriers ranging from resource constraints to communication barriers. Healthcare professionals advocate for targeted interventions, collaborative efforts, and policy measures to address these challenges effectively. The findings contribute to the evidence base for enhancing HBV control efforts in Iraq and emphasize the importance of tailored approaches to public health interventions.
Collapse
Affiliation(s)
- Mohammed A Jalal
- Department of Epidemiology, School of Public Health and Safety, Shahid Beheshti University of Medical Sciences, Tehran, IRN
| | - Manoochehr Karami
- Department of Epidemiology, School of Public Health and Safety, Shahid Beheshti University of Medical Sciences, Tehran, IRN
| | - Mahshid Namdari
- Department of Epidemiology, School of Public Health and Safety, Shahid Beheshti University of Medical Sciences, Tehran, IRN
| | - Faris Lami
- Department of Family and Community Medicine, College of Medicine in Baghdad University and Al-Sabtain University, Baghdad, IRQ
| | | | - Koorosh Etemad
- Department of Epidemiology, School of Public Health and Safety, Shahid Beheshti University of Medical Sciences, Tehran, IRN
| |
Collapse
|
38
|
Basimane-Bisimwa P, Koyaweda GW, Ngaïganam E, Vickos U, Sibiro OAD, Yambiyo BM, Sombié BS, Pélembi P, Moussa S, Bekondi C, Giles-Vernick T, Manirakiza A, Vray M, Komas NPJ. Seroprevalence and molecular characterization of viral hepatitis and HIV co-infection in the Central African Republic. PLoS One 2024; 19:e0291155. [PMID: 38722944 PMCID: PMC11081248 DOI: 10.1371/journal.pone.0291155] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2023] [Accepted: 04/19/2024] [Indexed: 05/13/2024] Open
Abstract
BACKGROUND The Central African Republic (CAR) is one of the countries with the highest prevalence of viral hepatitis infection in the world. Coinfection with HIV increases the morbidity and mortality beyond that of mono-infection with either hepatitis or HIV. The present study describes the geographic distribution of viral hepatitis infections and molecular characterization of these viruses in the CAR. METHODOLOGY Out of 12,599 persons enrolled during the fourth Multiple Indicator Cluster Survey of 2010 in the CAR, 10,621 Dried Blood Spot (DBS) samples were obtained and stored at -20°C. Of these DBS, 4,317 samples were randomly selected to represent all regions of the CAR. Serological tests for hepatitis B, D, and C viruses were performed using the ELISA technique. Molecular characterization was performed to identify strains. RESULTS Of the 4,317 samples included, 53.2% were from men and 46.8% from women. The HBsAg prevalence among participants was 12.9% and that HBc-Ab was 19.7%. The overall prevalence of HCV was 0.6%. Co-infection of HIV/HBV was 1.1% and that of HBV/HDV was 16.6%. A total of 77 HBV, 6 HIV, and 6 HDV strains were successfully sequenced, with 72 HBV (93.5%) strains belonging to genotype E and 5 (6.5%) strains belonging to genotype D. The 6 HDV strains all belonged to clade 1, while 4 recombinants subtype were identified among the 6 strains of HIV. CONCLUSION Our study found a high prevalence of HBV, HBV/HDV and HBV/HIV co-infection, but a low prevalence of HCV. CAR remains an area of high HBV endemicity. This study's data and analyses would be useful for establishing an integrated viral hepatitis and HIV surveillance program in the CAR.
Collapse
Affiliation(s)
- Parvine Basimane-Bisimwa
- Institut Pasteur de Bangui, Viral Hepatitis Laboratory, Bangui, Central African Republic
- Université Evangélique en Afrique (UEA), Bukavu, Democratic Republic of Congo
- International Center Advanced for Research and Training (ICART), Bukavu, Democratic Republic of Congo
- Hôpital Général de Référence de Panzi, Bukavu, Democratic Republic of Congo
| | | | - Edgarthe Ngaïganam
- Institut Pasteur de Bangui, Viral Hepatitis Laboratory, Bangui, Central African Republic
| | - Ulrich Vickos
- Laboratory of Arbovirus, Haemorrhagic Fevers, Institut Pasteur de Bangui, Emerging Virus and Zoonosis, Bangui, Central African Republic
| | | | | | - Benjamin Seydou Sombié
- Centre National de Recherche et de Formation sur le Paludisme, Ouagadougou, Burkina Faso
| | - Pulchérie Pélembi
- Institut Pasteur de Bangui, Service des Retrovirus-VIH, Bangui, Central African Republic
| | - Sandrine Moussa
- Institut Pasteur de Bangui, Service des Retrovirus-VIH, Bangui, Central African Republic
| | - Claudine Bekondi
- Institut Pasteur de Bangui, Centre de Ressources Biologiques, Bangui, Central African Republic
| | - Tamara Giles-Vernick
- Institut Pasteur-Université Paris Cité, Anthropology & Ecology of Disease Emergence Unit, INSERM, Paris, France
| | - Alexandre Manirakiza
- Institut Pasteur de Bangui, Epidemiology Service, Bangui, Central African Republic
| | - Muriel Vray
- Institut Pasteur-Université Paris Cité, Unit of Epidemiology of Emergent Infections, INSERM, Paris, France
| | | |
Collapse
|
39
|
Song J, Sun X, Zhou Y, Li S, Wu J, Yang L, Zhou D, Yang Y, Liu A, Lu M, Michael R, Qin L, Yang D. Early application of IFNγ mediated the persistence of HBV in an HBV mouse model. Antiviral Res 2024; 225:105872. [PMID: 38556058 DOI: 10.1016/j.antiviral.2024.105872] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2024] [Revised: 03/20/2024] [Accepted: 03/23/2024] [Indexed: 04/02/2024]
Abstract
The antiviral activity of interferon gamma (IFNγ) against hepatitis B virus (HBV) was demonstrated both in vivo and in vitro in a previous study. IFNγ can suppress HBV replication by accelerating the decay of replication-competent nucleocapsids of HBV. However, in this study, we found that the direct application of the mouse IFNγ (mIFNγ) expression plasmid to the liver of an HBV hydrodynamic injection (HI) mouse model led to the persistence of HBV, as indicated by sustained HBsAg and HBeAg levels in the serum as well as an increased percentage of the HBsAg positive mice, whereas the level of HBV DNA in the serum and the expression of HBcAg in the liver were inhibited at the early stage after HI. Meanwhile, we found that the productions of both HBcAb and HBsAb were suppressed after the application of mIFNγ. In addition, we found that HBV could be effectively inhibited in mice immunized with HBsAg expression plasmid before the application of mIFNγ. Furthermore, mIFNγ showed antiviral effect and promoted the production of HBsAb when the mice subjected to the core-null HBV plasmid. These results indicate that the application of mIFNγ in the HBV HI mouse model, the mice showed defective HBcAg-specific immunity that impeded the production of HBcAb and HBsAb, finally allowing the persistence of the virus. Moreover, IFNγ-induced negative immune regulatory factors also play an important role in virus persistence.
Collapse
Affiliation(s)
- Jingjiao Song
- Experimental Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China.
| | - Xiliang Sun
- Clinical Laboratory, Qingdao West Coast New District People's Hospital, Shandong, PR China.
| | - Yun Zhou
- Department of Infectious Diseases, Union Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China; Key Laboratory of Receptors-mediated Gene Regulation and Drug Discovery, School of Medicine, Henan University, Kaifeng, PR China.
| | - Sheng Li
- Department of Infectious Diseases, Union Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China.
| | - Jun Wu
- Department of Infectious Diseases, Union Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China.
| | - Lu Yang
- Experimental Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China.
| | - Di Zhou
- Experimental Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China.
| | - Yan Yang
- Experimental Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China.
| | - Anding Liu
- Experimental Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China.
| | - Mengji Lu
- Institute of Virology, University Hospital of Essen, University of Duisburg-Essen, Essen, Germany.
| | | | - Li Qin
- Department of Dermatology, Traditional Chinese and Western Medicine Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, Hubei, PR China.
| | - Dongliang Yang
- Experimental Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China; Department of Infectious Diseases, Union Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China.
| |
Collapse
|
40
|
Yanagisawa Y, Imai S, Kizaki H, Hori S. A cross-sectional survey of hepatitis B virus screening in patients who received immunosuppressive therapy for rheumatoid arthritis in Japan. J Pharm Health Care Sci 2024; 10:18. [PMID: 38637884 PMCID: PMC11025209 DOI: 10.1186/s40780-024-00339-9] [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: 01/16/2024] [Accepted: 04/15/2024] [Indexed: 04/20/2024] Open
Abstract
BACKGROUND Patients with a history of hepatitis B virus (HBV) infection who are receiving immunosuppressive therapy are at risk of HBV reactivation and disease. Therefore, HBV screening is required prior to administering antirheumatic drugs with immunosuppressive effects. This study aimed to determine the status of hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HBcAb), and hepatitis B surface antibody (HBsAb) screening prior to the initiation of drug therapy, including new antirheumatic drugs, in patients with rheumatoid arthritis. METHODS This retrospective cross-sectional study used data from April 2014 to August 2022 from the Japanese hospital-based administrative claims database. The inclusion criteria were rheumatoid arthritis and first prescription date of antirheumatic drugs. RESULTS A total of 82,282 patients with rheumatoid arthritis who were first prescribed antirheumatic drugs between April 2016 and August 2022 were included. Of the eligible patients, 9.7% (n=7,959) were screened for all HBV (HBsAg, HBsAb, and HbcAb) within 12 months prior to the date of initial prescription. The HBsAg test was performed in 30.0% (n=24,700), HBsAb test in 11.8% (n=9,717), and HBcAb test in 13.1% (n=10,824) of patients. The proportion of patients screened for HBV infection has been increasing since 2018; however, the proportion of patients screened for rheumatoid arthritis remains low. CONCLUSIONS Our findings suggest that HBV screening may be insufficient in patients who received antirheumatic drugs. With the increasing use of new immunosuppressive antirheumatic drugs, including biological agents, healthcare providers should understand the risk of HBV reactivation and conduct appropriate screening.
Collapse
Affiliation(s)
- Yuki Yanagisawa
- Division of Drug Informatics, Keio University Faculty of Pharmacy, 1-5-30 Shibakoen, Minato-ku, Tokyo, 105-8512, Japan
| | - Shungo Imai
- Division of Drug Informatics, Keio University Faculty of Pharmacy, 1-5-30 Shibakoen, Minato-ku, Tokyo, 105-8512, Japan.
| | - Hayato Kizaki
- Division of Drug Informatics, Keio University Faculty of Pharmacy, 1-5-30 Shibakoen, Minato-ku, Tokyo, 105-8512, Japan
| | - Satoko Hori
- Division of Drug Informatics, Keio University Faculty of Pharmacy, 1-5-30 Shibakoen, Minato-ku, Tokyo, 105-8512, Japan
| |
Collapse
|
41
|
Gómez-Moreno A, Ploss A. Mechanisms of Hepatitis B Virus cccDNA and Minichromosome Formation and HBV Gene Transcription. Viruses 2024; 16:609. [PMID: 38675950 PMCID: PMC11054251 DOI: 10.3390/v16040609] [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: 03/13/2024] [Revised: 04/11/2024] [Accepted: 04/13/2024] [Indexed: 04/28/2024] Open
Abstract
Hepatitis B virus (HBV) is the etiologic agent of chronic hepatitis B, which puts at least 300 million patients at risk of developing fibrosis, cirrhosis, and hepatocellular carcinoma. HBV is a partially double-stranded DNA virus of the Hepadnaviridae family. While HBV was discovered more than 50 years ago, many aspects of its replicative cycle remain incompletely understood. Central to HBV persistence is the formation of covalently closed circular DNA (cccDNA) from the incoming relaxed circular DNA (rcDNA) genome. cccDNA persists as a chromatinized minichromosome and is the major template for HBV gene transcription. Here, we review how cccDNA and the viral minichromosome are formed and how viral gene transcription is regulated and highlight open questions in this area of research.
Collapse
Affiliation(s)
| | - Alexander Ploss
- Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA
| |
Collapse
|
42
|
Abebe AD, Assefa M, Belete D, Ferede G. Seroprevalence of Hepatitis B and C Viruses and Their Associated Factors Among Military Personnel at Military Camps in Central Gondar, Ethiopia: A Cross-Sectional Study. Infect Drug Resist 2024; 17:1407-1417. [PMID: 38628243 PMCID: PMC11019156 DOI: 10.2147/idr.s455562] [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: 12/18/2023] [Accepted: 04/05/2024] [Indexed: 04/19/2024] Open
Abstract
Background Globally, viral hepatitis is a leading cause of death and is highly prevalent in Ethiopia. Military personnel are more vulnerable to hepatitis B virus (HBV) and hepatitis C virus (HCV) infections, and there are no data on such populations in the study area. Therefore, this study aimed to determine the seroprevalence of HBV and HCV infections and their associated factors among military personnel in military camps in Central Gondar, Ethiopia. Materials and Methods This institutional-based cross-sectional study was conducted with 277 military personnel from April to August 2022 at military camps in Central Gondar, Ethiopia. A systematic random sampling technique was used to select the study participants. Sociodemographic and other relevant data were collected using a structured questionnaire. Five milliliters of venous blood were collected using a vacutainer tube and tested for hepatitis B surface antigens and anti-hepatitis C virus antibodies using an enzyme-linked immunosorbent assay. Data were analyzed using STATA version 14 software and logistic regression models were used to determine the association between HBV/HCV infection and risk factors. Results Out of 277 participants, the overall seroprevalence of HBV and HCV infections was 19 (6.9%) and 9 (3.3%), respectively. The rate of HBV and HCV co-infection was 2 (0.7%). Having multiple sexual partners (p = 0.048), frequent alcohol use (p = 0.034), hospitalization (p = 0.014), and history of receiving injections from traditional practitioners (p = 0.040) were significant predictors of HBV infection. In contrast, a history of blood transfusion (p = 0.048) and sexually transmitted infections (p = 0.039) were significant risk factors for HCV infection. Conclusion and Recommendations An intermediate prevalence of HBV and HCV infections was observed among the military personnel. Continuous screening, adherence to healthcare service guidelines, and strengthening of vaccination are crucial for preventing HBV and HCV infections.
Collapse
Affiliation(s)
- Ayanaw Dinku Abebe
- Department of Medical Microbiology, School of Biomedical and Laboratory Sciences, College of Medicine and Health Sciences, University of Gondar, Gondar, Ethiopia
| | - Muluneh Assefa
- Department of Medical Microbiology, School of Biomedical and Laboratory Sciences, College of Medicine and Health Sciences, University of Gondar, Gondar, Ethiopia
| | - Debaka Belete
- Department of Medical Microbiology, School of Biomedical and Laboratory Sciences, College of Medicine and Health Sciences, University of Gondar, Gondar, Ethiopia
| | - Getachew Ferede
- Department of Medical Microbiology, School of Biomedical and Laboratory Sciences, College of Medicine and Health Sciences, University of Gondar, Gondar, Ethiopia
| |
Collapse
|
43
|
Buechter M, Günther AM, Manka P, Gerken G, Kahraman A. Factors Positively Correlated with Hepatitis B Surface Antigen Seroconversion in Chronic Hepatitis B. J Pers Med 2024; 14:390. [PMID: 38673017 PMCID: PMC11051014 DOI: 10.3390/jpm14040390] [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: 01/25/2024] [Revised: 03/25/2024] [Accepted: 03/27/2024] [Indexed: 04/28/2024] Open
Abstract
BACKGROUND AND AIMS Chronic hepatitis B virus (HBV) infection is a global public health challenge since more than 250 million individuals are affected worldwide. Since different treatment modalities are available and not all patients are candidates for antiviral treatment, biomarkers that potentially predict the possibility of HBsAg clearance and seroconversion may be useful in clinical practice. PATIENTS AND METHODS In this retrospective study, we aimed to identify factors positively correlated with HBsAg seroconversion in a large cohort of 371 chronic hepatitis B patients treated at a German tertial center between 2005 and 2020. RESULTS Seroconversion occurred in 25/371 (6.7%) and HBsAg loss in 29/371 patients (7.8%) with chronic HBV infection. Antiviral therapy was associated with a lower chance of seroconversion (seroconversion antiviral therapy 14/260 (5.4%) vs. therapy-naïve patients 11/111 (9.9%), p = 0.027). Seroconversion rates were higher in patients with (very) low titers of HBV DNA (best cut-off value 357 IU/mL) and quantitative HBsAg. The best cut-off value with regard to seroconversion was 357 IU/mL for HBV DNA (AUC 0.693 (95%-CI 0.063-0.422), sensitivity 0.714, specificity 0.729; p < 0.0005) and 33,55 IU/mL for HBsAg (AUC 0.794 (95%-CI 0.651-0.937), sensitivity 0.714, specificity 0.949; p < 0.0005). However, male gender was positively associated with seroconversion (seroconversion: males 7.6% vs. females 2.7%, p = 0.036). CONCLUSIONS Treatment-naïve male chronic HBV patients with low viral load and inflammatory activity have the best chance to achieve seroconversion. In the absence of cirrhosis, antiviral therapy should therefore not be performed in this patient collective.
Collapse
Affiliation(s)
- Matthias Buechter
- Department of Gastroenterology and Hepatology, University Clinic of Essen, University of Duisburg-Essen, 45147 Essen, Germany; (A.M.G.); (G.G.); (A.K.)
- Department of Gastroenterology and Hepatology, Elisabeth Hospital, 58638 Iserlohn, Germany
| | - Arne Maria Günther
- Department of Gastroenterology and Hepatology, University Clinic of Essen, University of Duisburg-Essen, 45147 Essen, Germany; (A.M.G.); (G.G.); (A.K.)
| | - Paul Manka
- Department of Internal Medicine, University Hospital Knappschaftskrankenhaus, Ruhr-University Bochum, 44801 Bochum, Germany;
| | - Guido Gerken
- Department of Gastroenterology and Hepatology, University Clinic of Essen, University of Duisburg-Essen, 45147 Essen, Germany; (A.M.G.); (G.G.); (A.K.)
- Department of Gastroenterology and Hepatology, Helios Clinic, 42549 Velbert, Germany
| | - Alisan Kahraman
- Department of Gastroenterology and Hepatology, University Clinic of Essen, University of Duisburg-Essen, 45147 Essen, Germany; (A.M.G.); (G.G.); (A.K.)
- Department of Gastroenterology and Hepatology, Max Grundig Clinic, 77815 Bühl, Germany
| |
Collapse
|
44
|
Olakunde BO, Ifeorah IM, Adeyinka DA, Olakunde OA, Ogundipe T, Olawepo JO, Ezeanolue EE. Immune response to hepatitis B vaccine among children under 5 years in Africa: a meta-analysis. Trop Med Health 2024; 52:28. [PMID: 38561838 PMCID: PMC10983738 DOI: 10.1186/s41182-024-00594-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2024] [Accepted: 03/17/2024] [Indexed: 04/04/2024] Open
Abstract
BACKGROUND Hepatitis B virus (HBV) infection in Africa is mostly acquired before the age of 5 years through vertical or horizontal routes. While all the countries in the World Health Organization African region have introduced HBV vaccination into their national immunization programs, the rate of protective immune response to HBV vaccine among children in Africa has not been systematically synthesized. In this study, we estimated the HBV vaccine seroprotection rate (defined as anti-HBs titer ≥ 10 IU/L) and the associated factors among under-five children who completed a primary series of HBV vaccination in Africa. METHODS We systematically searched PubMed, Web Science, and Scopus databases from inception to May 2022 for potentially eligible studies. The pooled seroprotection rate was estimated using a random-effects model with Freeman-Tukey double arcsine transformation and the associated factors were examined using odds ratio estimated by the DerSimonian and Laird method. RESULTS From the 1063 records identified, 29 studies with a total sample size of 9167 under-five children were included in the meta-analysis. The pooled seroprotection rate was 89.23% (95% CI 85.68-92.33%, I2 = 95.96%, p < 0.001). In the subgroup analyses, there was a significant difference in the rate by the assay method, vaccine dose, and vaccine combination. HIV-positive children had lower odds of achieving seroprotection when compared with HIV-negative children (OR = 0.22, 95%CI 0.12-0.40). CONCLUSIONS The majority of under-five children in Africa achieved seroprotection after completing three or four doses of HBV vaccine. However, the rate was lower among children living with HIV. This calls for interventions to timely identify and address nonresponse to HBV vaccine, particularly among immunosuppressed children.
Collapse
Affiliation(s)
- Babayemi O Olakunde
- Department of Community Prevention and Care Services, National Agency for the Control of AIDS, Abuja, Nigeria.
- Center for Translation and Implementation Research, University of Nigeria Nsukka, Enugu, Nigeria.
- Department of Population and Community Health, School of Public Health, University of North Texas Health Science Center, 3500 Camp Bowie Blvd., Fort Worth, TX, 76107, USA.
| | - Ijeoma M Ifeorah
- Center for Translation and Implementation Research, University of Nigeria Nsukka, Enugu, Nigeria
- Department of Medical Laboratory Sciences, University of Nigeria Nsukka, Enugu, Nigeria
| | - Daniel A Adeyinka
- Department of Research, Saskatchewan Health Authority, Saskatoon, SK, Canada
- Department of Public Health, Federal Ministry of Health, Abuja, Nigeria
| | - Olubunmi A Olakunde
- Department of Disease Control and Immunization, Ondo State Primary Health Care Development Agency, Ondo, Nigeria
| | | | - John O Olawepo
- Center for Translation and Implementation Research, University of Nigeria Nsukka, Enugu, Nigeria
- Department of Health Sciences, Northeastern University, Boston, MA, USA
| | - Echezona E Ezeanolue
- Center for Translation and Implementation Research, University of Nigeria Nsukka, Enugu, Nigeria
- Healthy Sunrise Foundation, Nevada, USA
| |
Collapse
|
45
|
Altın KH, Agel E. Development of Molecular-Based Screening Test for Hepatitis B Virus in Human Plasma Samples. Jpn J Infect Dis 2024; 77:97-104. [PMID: 38030268 DOI: 10.7883/yoken.jjid.2023.313] [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: 12/01/2023]
Abstract
Despite regular administration of hepatitis B virus (HBV) vaccine in several countries, the mortality rate associated with HBV remains significant. The antiviral medications available for the treatment of HBV infection do not suffice for the serious complications related to chronic HBV infection. Additionally, the serological tests fail to detect early viral replication preventing early treatment response. Recently, many studies have demonstrated the significant advantages of loop-mediated isothermal amplification (LAMP) over serological testing and polymerase chain reaction (PCR), for the rapid detection of microbial pathogens. Here we developed a rapid, sensitive, and portable system-integrative LAMP assay for the detection of HBV DNA in plasma samples. The final optimized assay was achieved with an amplification time of less than 45 min at 62°C. The assay showed 100% specificity, 92.20% sensitivity, and a detection limit of 10 copies/µL in 77 HBV-positive plasma samples with known Cq values. Our results showed that the colorimetric LAMP assay is sensitive, efficient, and supremely reliable for rapid detection of HBV, and may be potentially used as a screening test in areas with poor laboratory facilities and limited resource availability.
Collapse
Affiliation(s)
- Kevser Hanne Altın
- Department of Medical Microbiology, Faculty of Medicine, Istanbul Medipol University, Türkiye
| | - Esra Agel
- Biomaterials, Biomechanics and Bioelectronics Center of Excellence, TÜBİTAK Marmara Research Center, Türkiye
| |
Collapse
|
46
|
Huang XX, Lin Q, Li Y, Li L. Effects of Maternal Health During Pregnancy and Child Immunization on Mother-to-Child Transmission of Hepatitis B Virus: A Multicentre, Large-Sample Study in Southeast China. Infect Drug Resist 2024; 17:989-1001. [PMID: 38505249 PMCID: PMC10949338 DOI: 10.2147/idr.s443172] [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: 10/25/2023] [Accepted: 02/19/2024] [Indexed: 03/21/2024] Open
Abstract
Purpose High hepatitis B infection rates in China are a major public health issue, and mother-to-child transmission (MTCT) is a significant risk factor. Patients and Methods This study was conducted with a prospective multicentre design from January 2021 to December 2022 in 245 hospitals providing midwifery services in southeastern China. The participants were pregnant women who were positive for hepatitis B surface antigen (HBs Ag) and their children. The HBs Ag concentration was tested in children aged 8-12 months. The odds ratio for each risk factor was calculated by logistic regression analysis, and the decision tree model was used. Results A total of 5369 children born to hepatitis B-infected mothers between 8 and 12 months of age were enrolled, among whom 81 (1.51%) were positive for HBsAg. The risk factors for hepatitis B infection in 5369 children under one-year-old were a high intrauterine hepatitis B exposure level, a history of hepatitis B immunoglobulin (HBIG) delay beyond 12 hours after birth, and lack of full hepatitis B vaccine (HepB), with risks of 3.356 (1.223~9.209), 5.691 (1.931~16.773), and 5.137 (2.265~11.650), respectively. The discrimination accuracy of the decision tree was 98.5%. The risk factors for hepatitis B infection in 4542 children under one year old with high exposure risk were nonstandard treatment by the mother during pregnancy, HBIG delay beyond 12 hours after birth, and no complete HepB administration, with risks of 2.925 (1.063-8.047), 5.354 (1.806-15.871) and 5.147 (2.258-11.733), respectively. The discrimination accuracy of the decision tree was 98.3%. Conclusion To prevent mother-to-child transmission of hepatitis B, it is necessary to standardize the treatment of pregnant women with a high exposure risk of hepatitis B, implement combined vaccination within 12 hours of birth, and standardise the full course of HepB.
Collapse
Affiliation(s)
- Xin-Xin Huang
- The Ministry of Health, Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, Fujian Province, People’s Republic of China
| | - Quan Lin
- Department of Obstetrics, Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, Fujian Province, People’s Republic of China
| | - Yun Li
- Department of Obstetrics, Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, Fujian Province, People’s Republic of China
| | - Li Li
- Department of Obstetrics, Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, Fujian Province, People’s Republic of China
| |
Collapse
|
47
|
Dzudzor B, Nsowah KK, Agyemang S, Vento S, Amarh V, Boima V, Tachi K. Overt and occult hepatitis B virus infection detected among chronic kidney disease patients on haemodialysis at a Tertiary Hospital in Ghana. PLoS One 2024; 19:e0290917. [PMID: 38437229 PMCID: PMC10911607 DOI: 10.1371/journal.pone.0290917] [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: 08/23/2023] [Accepted: 02/17/2024] [Indexed: 03/06/2024] Open
Abstract
Hepatitis B virus (HBV) infection is endemic in Ghana and chronic kidney disease patients on haemodialysis are a high-risk group for HBV infection. We determined the prevalence of overt and occult HBV infection among haemodialysis patients at the Korle Bu Teaching Hospital in Ghana. 104 consenting End Stage Renal Disease patients on long-term haemodialysis were recruited for the study and their socio-demographic, clinical and laboratory information were obtained using structured questionnaire. All the participants were tested for the hepatitis B surface antigen (HBsAg). The HBsAg-negative participants were re-tested for hepatitis B surface antibody (HBsAb), hepatitis B core antibody (HBcAb) and HBV DNA using chemiluminescence and Roche COBAS Ampli-Prep/TaqMan analyser and real-time polymerase chain reaction. Eight (7.7%) of the total participants were positive for HBsAg. Among the 96 HBsAg-negative participants, 12.5% (12) were HBcAb-positive, 7.3% (7) had detectable HBV DNA (mean = 98.7±53.5 IU/mL) and 40.6% (39) were positive for HBsAb. Five out of the 7 HBV DNA-positive participants were males and only one participant was negative for HBcAb. Seventy-three out of the 96 HBsAg-negative participants were vaccinated and 37 of these vaccinated individuals had significant HBsAb titres (mean = 423.21± 380.72 IU/mL). Our data demonstrated that the prevalence of overt and occult HBV infection among the haemodialysis (HD) patients was 7.7% and 7.3%, respectively, and only 50.7% of those who showed proof of vaccination were protected from HBV infection.
Collapse
Affiliation(s)
- Bartholomew Dzudzor
- Department of Medical Biochemistry, University of Ghana Medical School, Korle-Bu, Ghana
| | - Kingsley Kwame Nsowah
- Department of Medical Biochemistry, University of Ghana Medical School, Korle-Bu, Ghana
| | | | - Sandro Vento
- Faculty of Medicine, University of Puthisastra, Phnom Penh, Cambodia
| | - Vincent Amarh
- Department of Medical Biochemistry, University of Ghana Medical School, Korle-Bu, Ghana
| | - Vincent Boima
- Department of Medicine and Therapeutics, University of Ghana Medical School, Korle-Bu, Ghana
| | - Kenneth Tachi
- Department of Medicine and Therapeutics, University of Ghana Medical School, Korle-Bu, Ghana
| |
Collapse
|
48
|
Kanduri SR, Peleg Y, Wadhwani S. Liver Disease-Associated Glomerulopathies. ADVANCES IN KIDNEY DISEASE AND HEALTH 2024; 31:147-156. [PMID: 38649219 DOI: 10.1053/j.akdh.2023.11.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/06/2023] [Revised: 10/11/2023] [Accepted: 11/22/2023] [Indexed: 04/25/2024]
Abstract
Hepatitis B virus (HBV) and hepatitis C virus (HCV) infect a significant number of individuals globally and their extra-hepatic manifestations, including glomerular disease, are well established. Additionally, liver disease-associated IgA nephropathy is the leading cause of secondary IgA nephropathy with disease course varying from asymptomatic urinary abnormalities to progressive kidney injury. Herein we provide an updated review on the epidemiology, pathogenesis, clinical manifestations, and treatment of HBV- and HCV-related glomerulonephritis as well as IgA nephropathy in patients with liver disease. The most common HBV-related glomerulonephritis is membranous nephropathy, although membranoproliferative glomerulonephritis and podocytopathies have been described. The best described HCV-related glomerulonephritis is cryoglobulinemic glomerulonephritis occurring in about 30% of patients with mixed cryoglobulinemic vasculitis. The mainstay of treatment for HBV-GN and HCV-GN is antiviral therapy, with significant improvement in outcomes since the emergence of the direct-acting antivirals. However, cases with severe pathology and/or a more aggressive disease trajectory can be offered a course of immunosuppression, commonly anti-CD20 therapy, particularly in the case of cryoglobulinemic glomerulonephritis.
Collapse
Affiliation(s)
- Swetha R Kanduri
- Department of Nephrology, Ochsner Health System, New Orleans, LA; Ochsner Clinical School, The University of Queensland, New Orleans, LA.
| | - Yonatan Peleg
- Division of Nephrology and Hypertension, Northwestern University Feinberg School of Medicine, Chicago, IL
| | - Shikha Wadhwani
- Division of Nephrology and Hypertension, Northwestern University Feinberg School of Medicine, Chicago, IL
| |
Collapse
|
49
|
Matrenec R, Oropeza CE, Dekoven E, Tarnow G, Maienschein-Cline M, Chau CS, Green SJ, McLachlan A. Ten-eleven translocation (Tet) methylcytosine dioxygenase-dependent viral DNA demethylation mediates in vivo hepatitis B virus (HBV) biosynthesis. J Virol 2024; 98:e0172123. [PMID: 38179947 PMCID: PMC10878274 DOI: 10.1128/jvi.01721-23] [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: 11/01/2023] [Accepted: 11/29/2023] [Indexed: 01/06/2024] Open
Abstract
Liver-specific ten-eleven translocation (Tet) methylcytosine dioxygenases 2 and 3 (Tet2 plus Tet3)-deficient hepatitis B virus (HBV) transgenic mice fail to support viral biosynthesis. The levels of viral transcription and replication intermediates are dramatically reduced. Hepatitis B core antigen is only observed in a very limited number of pericentral hepatocytes in a pattern that is similar to glutamate-ammonia ligase (Glul), a β-catenin target gene. HBV transcript abundance in adult Tet-deficient mice resembles that observed in wild-type neonatal mice. Furthermore, the RNA levels of several β-catenin target genes including Glul, Lhpp, Notun, Oat, Slc1a2, and Tbx3 in Tet-deficient mice were also similar to that observed in wild-type neonatal mice. As HBV transcription is regulated by β-catenin, these findings support the suggestion that neonatal Tet deficiency might limit β-catenin target gene expression, limiting viral biosynthesis. Additionally, HBV transgene DNA displays increased 5-methylcytosine (5mC) frequency at CpG sequences consistent with neonatal Tet deficiency being responsible for decreased developmental viral DNA demethylation mediated by 5mC oxidation to 5-hydroxymethylcytosine, a process that might be responsible for the reduction in cellular β-catenin target gene expression and viral transcription and replication.IMPORTANCEChronic hepatitis B virus (HBV) infection causes significant worldwide morbidity and mortality. There are no curative therapies available to resolve chronic HBV infections, and the small viral genome limits molecular targets for drug development. An alternative approach to drug development is to target cellular genes essential for HBV biosynthesis. In the liver, ten-eleven translocation (Tet) genes encode cellular enzymes that are not essential for postnatal mouse development but represent essential activities for viral DNA demethylation and transcription. Consequently, Tet inhibitors may potentially be developed into therapeutic agents capable of inducing and/or maintaining HBV covalently closed circular DNA methylation, resulting in transcriptional silencing and the resolution of chronic viral infection.
Collapse
Affiliation(s)
- Rachel Matrenec
- Department of Microbiology and Immunology, College of Medicine, University of Illinois, Chicago, Illinois, USA
| | - Claudia E. Oropeza
- Department of Microbiology and Immunology, College of Medicine, University of Illinois, Chicago, Illinois, USA
| | - Eddie Dekoven
- Department of Microbiology and Immunology, College of Medicine, University of Illinois, Chicago, Illinois, USA
| | - Grant Tarnow
- Department of Microbiology and Immunology, College of Medicine, University of Illinois, Chicago, Illinois, USA
| | - Mark Maienschein-Cline
- Research Informatics Core, Research Resources Center, University of Illinois, Chicago, Illinois, USA
| | - Cecilia S. Chau
- Genomics and Microbiome Core Facility, Rush University Medical Center, Chicago, Illinois, USA
| | - Stefan J. Green
- Genomics and Microbiome Core Facility, Rush University Medical Center, Chicago, Illinois, USA
| | - Alan McLachlan
- Department of Microbiology and Immunology, College of Medicine, University of Illinois, Chicago, Illinois, USA
| |
Collapse
|
50
|
Olakunde BO, Itanyi IU, Onyeka TC, Paintsil E, Torpey K, Lasebikan N, Chigbu CO, Ezeanolue EE. Hepatitis B vaccine birth dose coverage among hepatitis B-exposed and hepatitis B-unexposed infants: evidence from the Healthy Beginning Initiative program in Benue State, Nigeria. Pan Afr Med J 2024; 47:67. [PMID: 38681098 PMCID: PMC11055182 DOI: 10.11604/pamj.2024.47.67.40466] [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: 05/18/2023] [Accepted: 01/16/2024] [Indexed: 05/01/2024] Open
Abstract
Introduction Nigeria offers universal hepatitis B birth-dose vaccine (HepB-BD) for the prevention and control of hepatitis B (HepB). While prior studies suggest low coverage of HepB-BD in Nigeria, there is a paucity of evidence on the association between the uptake of HepB-BD and maternal HepB status. This study aimed to determine HepB-BD coverage and the associated factors among infants of HepB-positive and -negative women in Nigeria. Methods the study was a secondary analysis of data from the Healthy Beginning Initiative program conducted between June 2016 and October 2018 in Benue State, Nigeria. The analysis was restricted to data from a cohort of 6269 mothers who had HepB screening during pregnancy and completed the HepB infant immunization question in the post-delivery survey. The association between the coverage of HepB-BD and maternal HepB status, sociodemographic characteristics, and obstetric factors were determined using crude and adjusted relative risks. Results about 10% of the women tested HepB positive. The coverage of HepB-BD was 64% (63.2% among infants of HepB-positive mothers and 63.8% among HepB-negative mothers). The likelihood of infants of HepB-positive mothers receiving HepB-BD was not significantly different from infants of HepB-negative mothers (aRR=0.97, 95%CI= 0.92-1.04). Among HepB-positive mothers, infants of mothers younger than 20 years (aRR=1.49, 95%CI=1.03-2.16) or those who received antenatal care (aRR=1.41, 95%CI=1.16-1.71) were more likely to receive HepB-BD, while mothers with no previous pregnancies (aRR=0.73, 95%CI=0.59-0.91) were less likely to receive HepB-BD. Among HepB-negative mothers, infants of less-educated mothers were less likely to receive HepB-BD (aRR=0.96, 95%CI=0.92-0.99), whereas infants of mothers who received antenatal care (aRR=1.23, 95%CI=1.16-1.31) or had an institutional delivery were more likely (aRR=1.29, 95%CI=1.23-1.36) to receive HepB-BD. Conclusion: our findings highlight the need to improve HepB-BD uptake, particularly among HepB-exposed infants who are at risk of perinatal transmission of HepB.
Collapse
Affiliation(s)
- Babayemi Oluwaseun Olakunde
- Department of Community Prevention and Care Services, National Agency for the Control of AIDS, Abuja, Nigeria
- Center for Translation and Implementation Research, University of Nigeria, Nsukka, Enugu, Nigeria
| | - Ijeoma Uchenna Itanyi
- Center for Translation and Implementation Research, University of Nigeria, Nsukka, Enugu, Nigeria
- Department of Community Medicine, College of Medicine, University of Nigeria, Nsukka, Enugu, Nigeria
| | - Tonia Chinyelu Onyeka
- Center for Translation and Implementation Research, University of Nigeria, Nsukka, Enugu, Nigeria
- Department of Anesthesia/Pain and Palliative Care Unit, College of Medicine, University of Nigeria, Nsukka, Nigeria
| | - Elijah Paintsil
- Department of Pediatrics, Yale School of Medicine, New Haven, CT 06510, USA
- Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, CT 06510, USA
- Department of Pharmacology, Yale School of Medicine, New Haven, CT, USA
| | - Kwasi Torpey
- Department of Population, Family and Reproductive Health, School of Public Health, University of Ghana, Legon-Accra, Ghana
| | - Nwamaka Lasebikan
- Center for Translation and Implementation Research, University of Nigeria, Nsukka, Enugu, Nigeria
- Department of Radiation Medicine, College of Medicine, University of Nigeria, Nsukka, Enugu, Nigeria
| | - Chibuike Ogwuegbu Chigbu
- Center for Translation and Implementation Research, University of Nigeria, Nsukka, Enugu, Nigeria
- Department of Obstetrics and Gynaecology, College of Medicine, University of Nigeria, Nsukka, Enugu, Nigeria
| | - Echezona Edozie Ezeanolue
- Center for Translation and Implementation Research, University of Nigeria, Nsukka, Enugu, Nigeria
- Department of Paediatrics, College of Medicine, University of Nigeria, Nsukka, Enugu, Nigeria
- Healthy Sunrise Foundation, Nevada, USA
| |
Collapse
|