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Zhong G, Jiang ZH, Wang XY, Chen QY, Zhang LJ, Hu LP, Huang ML, Huang YB, Hu X, Zhang WW, Harrison TJ, Fang ZL. Increasing Prevalence of Occult HBV Infection in Adults Vaccinated Against Hepatitis B at Birth. Vaccines (Basel) 2025; 13:174. [PMID: 40006721 PMCID: PMC11860204 DOI: 10.3390/vaccines13020174] [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: 12/11/2024] [Revised: 02/02/2025] [Accepted: 02/05/2025] [Indexed: 02/27/2025] Open
Abstract
BACKGROUND/OBJECTIVES Immunization with the hepatitis B vaccine is the most effective means of preventing acute HBV infection. However, whether the primary vaccination of infants confers lifelong immunity remains controversial. Therefore, the ongoing surveillance of vaccine recipients is required. METHODS A longitudinal study was carried out based on LongAn county, one of the five clinical trial centers for hepatitis B immunization in China in the 1980s. Serum samples were collected and tested for HBV serological markers and DNA. RESULTS A total of 637 subjects born in 1987-1993 were recruited, including 503 males and 134 females. The total prevalence of HBsAg was 3.9%. The prevalence in females (8.2%) was significantly higher than that in males (2.8%) (p = 0.004). The prevalence of anti-HBc in females (52.2%) was also significantly higher than that in males (41.2%) (p = 0.021). The prevalence of anti-HBs was 42.7% and did not differ significantly between males (41.7%) and females (46.3%) (p = 0.347). Compared to data from surveillance over the last ten years, the positivity rate of HBsAg did not increase. The positivity rate of anti-HBs decreased significantly (p = 0.049) while that of anti-HBc increased significantly (p = 0.001). The prevalence of occult HBV infection (OBI) in 2024 (6.0%) was significantly higher than that in 2017 (1.6%) (p = 0.045). Subjects diagnosed with OBI in 2017 maintained occult infection in 2024. CONCLUSIONS Neonatal HBV vaccination maintained effective protection for at least 37 years. However, the prevalence of OBI increases with age in those vaccinated at birth, raising a new issue of how to prevent and control OBI in the post-universal infant vaccination era.
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Affiliation(s)
- Ge Zhong
- Guangxi Zhuang Autonomous Region Center for Disease Prevention and Control, Guangxi Key Laboratory for the Prevention and Control of Viral Hepatitis, Nanning 530028, China; (G.Z.); (Z.-H.J.); (X.-Y.W.); (Q.-Y.C.); (L.-J.Z.); (L.-P.H.); (M.-L.H.); (Y.-B.H.); (X.H.); (W.-W.Z.)
| | - Zhi-Hua Jiang
- Guangxi Zhuang Autonomous Region Center for Disease Prevention and Control, Guangxi Key Laboratory for the Prevention and Control of Viral Hepatitis, Nanning 530028, China; (G.Z.); (Z.-H.J.); (X.-Y.W.); (Q.-Y.C.); (L.-J.Z.); (L.-P.H.); (M.-L.H.); (Y.-B.H.); (X.H.); (W.-W.Z.)
| | - Xue-Yan Wang
- Guangxi Zhuang Autonomous Region Center for Disease Prevention and Control, Guangxi Key Laboratory for the Prevention and Control of Viral Hepatitis, Nanning 530028, China; (G.Z.); (Z.-H.J.); (X.-Y.W.); (Q.-Y.C.); (L.-J.Z.); (L.-P.H.); (M.-L.H.); (Y.-B.H.); (X.H.); (W.-W.Z.)
| | - Qin-Yan Chen
- Guangxi Zhuang Autonomous Region Center for Disease Prevention and Control, Guangxi Key Laboratory for the Prevention and Control of Viral Hepatitis, Nanning 530028, China; (G.Z.); (Z.-H.J.); (X.-Y.W.); (Q.-Y.C.); (L.-J.Z.); (L.-P.H.); (M.-L.H.); (Y.-B.H.); (X.H.); (W.-W.Z.)
| | - Lu-Juan Zhang
- Guangxi Zhuang Autonomous Region Center for Disease Prevention and Control, Guangxi Key Laboratory for the Prevention and Control of Viral Hepatitis, Nanning 530028, China; (G.Z.); (Z.-H.J.); (X.-Y.W.); (Q.-Y.C.); (L.-J.Z.); (L.-P.H.); (M.-L.H.); (Y.-B.H.); (X.H.); (W.-W.Z.)
| | - Li-Ping Hu
- Guangxi Zhuang Autonomous Region Center for Disease Prevention and Control, Guangxi Key Laboratory for the Prevention and Control of Viral Hepatitis, Nanning 530028, China; (G.Z.); (Z.-H.J.); (X.-Y.W.); (Q.-Y.C.); (L.-J.Z.); (L.-P.H.); (M.-L.H.); (Y.-B.H.); (X.H.); (W.-W.Z.)
| | - Mei-Lin Huang
- Guangxi Zhuang Autonomous Region Center for Disease Prevention and Control, Guangxi Key Laboratory for the Prevention and Control of Viral Hepatitis, Nanning 530028, China; (G.Z.); (Z.-H.J.); (X.-Y.W.); (Q.-Y.C.); (L.-J.Z.); (L.-P.H.); (M.-L.H.); (Y.-B.H.); (X.H.); (W.-W.Z.)
- School of Preclinical Medicine, Guangxi Medical University, Nanning 530021, China
| | - Yu-Bi Huang
- Guangxi Zhuang Autonomous Region Center for Disease Prevention and Control, Guangxi Key Laboratory for the Prevention and Control of Viral Hepatitis, Nanning 530028, China; (G.Z.); (Z.-H.J.); (X.-Y.W.); (Q.-Y.C.); (L.-J.Z.); (L.-P.H.); (M.-L.H.); (Y.-B.H.); (X.H.); (W.-W.Z.)
- School of Preclinical Medicine, Guangxi Medical University, Nanning 530021, China
| | - Xue Hu
- Guangxi Zhuang Autonomous Region Center for Disease Prevention and Control, Guangxi Key Laboratory for the Prevention and Control of Viral Hepatitis, Nanning 530028, China; (G.Z.); (Z.-H.J.); (X.-Y.W.); (Q.-Y.C.); (L.-J.Z.); (L.-P.H.); (M.-L.H.); (Y.-B.H.); (X.H.); (W.-W.Z.)
- School of Preclinical Medicine, Guangxi Medical University, Nanning 530021, China
| | - Wei-Wei Zhang
- Guangxi Zhuang Autonomous Region Center for Disease Prevention and Control, Guangxi Key Laboratory for the Prevention and Control of Viral Hepatitis, Nanning 530028, China; (G.Z.); (Z.-H.J.); (X.-Y.W.); (Q.-Y.C.); (L.-J.Z.); (L.-P.H.); (M.-L.H.); (Y.-B.H.); (X.H.); (W.-W.Z.)
| | - Tim J. Harrison
- Division of Medicine, University College London Medical School, London WC1E 6BT, UK;
| | - Zhong-Liao Fang
- Guangxi Zhuang Autonomous Region Center for Disease Prevention and Control, Guangxi Key Laboratory for the Prevention and Control of Viral Hepatitis, Nanning 530028, China; (G.Z.); (Z.-H.J.); (X.-Y.W.); (Q.-Y.C.); (L.-J.Z.); (L.-P.H.); (M.-L.H.); (Y.-B.H.); (X.H.); (W.-W.Z.)
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Wibowo DP, Agustiningsih A, Jayanti S, Sukowati CHC, El Khobar KE. Exploring the impact of hepatitis B immunoglobulin and antiviral interventions to reduce vertical transmission of hepatitis B virus. World J Exp Med 2024; 14:95960. [PMID: 39713069 PMCID: PMC11551711 DOI: 10.5493/wjem.v14.i4.95960] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/23/2024] [Revised: 08/16/2024] [Accepted: 09/02/2024] [Indexed: 10/31/2024] Open
Abstract
Hepatitis B virus (HBV) infection is a major public health burden. In HBV endemic regions, high prevalence is also correlated with the infections acquired in infancy through perinatal transmission or early childhood exposure to HBV, the so-called mother-to-child transmission (MTCT). Children who are infected with HBV at a young age are at higher risk of developing chronic HBV infection than those infected as adults, which may lead to worse clinical outcome. To reduce the incidence of HBV MTCT, several interventions for the infants or the mothers, or both, are already carried out. This review explores the newest information and approaches available in literature regarding HBV MTCT prevalence and its challenges, especially in high HBV endemic countries. This covers HBV screening in pregnant women, prenatal intervention, infant immunoprophylaxis, and post-vaccination serological testing for children.
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Affiliation(s)
- Dhita Prabasari Wibowo
- Eijkman Research Center for Molecular Biology, Research Organization for Health, National Research and Innovation Agency of Indonesia, Jakarta 10430, Indonesia
- Postgraduate School, Faculty of Medicine, Universitas Hasanuddin, Makassar 90245, Indonesia
| | - Agustiningsih Agustiningsih
- Eijkman Research Center for Molecular Biology, Research Organization for Health, National Research and Innovation Agency of Indonesia, Jakarta 10430, Indonesia
| | - Sri Jayanti
- Eijkman Research Center for Molecular Biology, Research Organization for Health, National Research and Innovation Agency of Indonesia, Jakarta 10430, Indonesia
| | - Caecilia H C Sukowati
- Eijkman Research Center for Molecular Biology, Research Organization for Health, National Research and Innovation Agency of Indonesia, Jakarta 10430, Indonesia
- Department of Liver Cancer, Fondazione Italiana Fegato ONLUS, Trieste 34149, Italy
| | - Korri Elvanita El Khobar
- Eijkman Research Center for Molecular Biology, Research Organization for Health, National Research and Innovation Agency of Indonesia, Jakarta 10430, Indonesia
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Eilard A, Andersson ME, Wejstål R, Norkrans G, Lindh M. Occult hepatitis B infection in children born to HBeAg-positive women confers a low long-term risk for HBsAg-positive infection. Infection 2024; 52:2351-2357. [PMID: 38727925 PMCID: PMC11621201 DOI: 10.1007/s15010-024-02290-1] [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: 02/22/2024] [Accepted: 05/01/2024] [Indexed: 12/07/2024]
Abstract
PURPOSE Mother-to-child transmission (MTCT) has been the main cause of chronic hepatitis B virus (HBV) infection, particularly in East Asia. Hepatitis B immunoglobulin (HBIG) and vaccination given directly after birth effectively prevents hepatitis B surface antigen (HBsAg)-positive (overt) HBV infection, but occult hepatitis B infection (OBI) may develop despite adequate prophylaxis. The aim of this study was to investigate the long-term outcome in children born to mothers with very high HBV DNA levels with special focus on children discovered in early childhood with OBI. METHODS One-year and long-term outcome regarding overt and occult HBV infection were analysed in 66 children born to hepatitis B e antigen (HBeAg)-positive mothers, and were compared with one-year outcome in 69 children born to HBeAg-negative mothers. The children were born between 1998 and 2018. RESULTS Six children born to HBeAg-positive mothers developed overt chronic HBV infection, in two cases after normal pregnancies and despite HBIG and vaccination, but never when nucleotide analogue treatment was given during pregnancy. OBI with HBV DNA detected in serum in the absence of surface antigen (HBsAg) was observed in four children at the age of 1 year. One of them was transiently HBsAg-positive at the age of 7 years. At long-term follow-up, six children had overt chronic infection, one had OBI and six had previous OBI or positive anti-HBc suggesting resolved unidentified infections. CONCLUSION The results indicate that children born to mothers with high HBV DNA levels have approximately 10% risk to develop OBI despite antiviral treatment, vaccination and HBIG, but that such OBI confers a minimal long-term risk for overt infection, at least in immunocompetent children.
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Affiliation(s)
- Anders Eilard
- Department of Infectious Diseases, University of Gothenburg, 413 46, Gothenburg, Sweden.
- Department of Infectious Diseases, Sahlgrenska University Hospital, 416 85, Gothenburg, Sweden.
| | - Maria E Andersson
- Department of Infectious Diseases, University of Gothenburg, 413 46, Gothenburg, Sweden
| | - Rune Wejstål
- Department of Infectious Diseases, Sahlgrenska University Hospital, 416 85, Gothenburg, Sweden
| | - Gunnar Norkrans
- Department of Infectious Diseases, Sahlgrenska University Hospital, 416 85, Gothenburg, Sweden
| | - Magnus Lindh
- Department of Infectious Diseases, University of Gothenburg, 413 46, Gothenburg, Sweden
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Delghandi S, Raoufinia R, Shahtahmasbi S, Meshkat Z, Gouklani H, Gholoobi A. An overview of occult hepatitis B infection (OBI) with emphasis on HBV vaccination. Heliyon 2024; 10:e37097. [PMID: 39281486 PMCID: PMC11402251 DOI: 10.1016/j.heliyon.2024.e37097] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2024] [Revised: 08/25/2024] [Accepted: 08/27/2024] [Indexed: 09/18/2024] Open
Abstract
Background The prevalence of chronic hepatitis B virus (HBV) poses a significant threat to the lives of 257 million individuals globally, potentially resulting in severe outcomes such as liver cirrhosis or hepatocellular carcinoma. Among the existing preventive measures, yeast-derived vaccines have proven to be the most efficacious approach in combatting hepatitis B. Nonetheless, as scientific inquiries focus more on occult HBV infection (OBI) in vaccinated persons and the lingering risk of vertical transmission affecting 10-30 % of babies born to HBsAg-positive mothers, there is a growing apprehension regarding the inability of HBV vaccines to ensure complete immunity. This study aims to offer a more comprehensive understanding of the implications of widespread HBV vaccination initiatives on OBI while tackling the primary limitations associated with current vaccine formulations. Methods The exploration was conducted on PubMed, Scopus, and Web of Science databases to pinpoint research on OBI within vaccinated cohorts. A sum of 76 suitable studies was recognized. Discussion Multiple studies have documented the occurrence of OBI in fully vaccinated individuals, including both the general population and high-risk groups, such as newborns born to HBsAg-positive mothers. Factors contributing to vaccine failures include low-level anti-HBs antibodies, high maternal viral loads in mother-to-child transmission cases, as well as the presence of vaccine escape mutants and heterologous HBV genotypes. However, further research is needed to precisely understand the impact of active immunization on the emergence of OBI in vaccinated populations. Nonetheless, it is apparent that the advancement of more effective HBV vaccines could potentially lead to the extinction of HBV.
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Affiliation(s)
- Sara Delghandi
- Medical Genetics Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
- Division of Immunology and Genomic Medicine, Center for Cancer Immunotherapy and Immunobiology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Ramin Raoufinia
- Noncommunicable Diseases Research Center, Neyshabur University of Medical Sciences, Neyshabur, Iran
- Medical Genetics Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Sahar Shahtahmasbi
- Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Zahra Meshkat
- Antimicrobial Resistance Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Hamed Gouklani
- Infectious and Tropical Diseases Research Center, Hormozgan Health Institute, Hormozgan University of Medical Sciences, Bandar Abbas, Iran
| | - Aida Gholoobi
- Medical Genetics Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
- Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
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Li Y, Song Y, Xiao Y, Wang T, Li L, Liu M, Li J, Wang J. The Characteristic of HBV Quasispecies Is Related to Occult HBV Infection of Infants Born to Highly Viremic Mothers. Viruses 2024; 16:1104. [PMID: 39066265 PMCID: PMC11281566 DOI: 10.3390/v16071104] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2024] [Revised: 06/28/2024] [Accepted: 07/08/2024] [Indexed: 07/28/2024] Open
Abstract
Although a combination of immunoprophylaxis and antiviral therapy can effectively prevent mother-to-child transmission (MTCT) of hepatitis B virus (HBV), a considerable number of infants born to highly viremic mothers still develop occult HBV infection (OBI). To uncover the virological factor and risk predictor for OBI in infants, we found that the diversity and complexity of maternal HBV quasispecies in the case group were lower than those in the control group. Mutations with significant differences between the two groups were most enriched in the NTCPbd and PreC regions. Genetic distance at the amino-acid level of the PreC region, especially the combination of three amino-acid mutations in the PreC region, could strongly predict the risk of OBI in infants. HBV quasispecies in OBI infants were highly complex, and the non-synonymous substitutions were mainly found in the RT and HBsAg regions. The sK47E (rtQ55R) and sP49L mutations in OBI infants might contribute to OBI through inhibiting the production of HBV DNA and HBsAg, respectively. This study found the potential virological factors and risk predictors for OBI in infants born to highly viremic mothers, which might be helpful for controlling OBI in infants.
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Affiliation(s)
- Yi Li
- Department of Microbiology & Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China
- Department of Clinical Laboratory, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
- Graduate School, Peking Union Medical College, Chinese Academy of Medical Science, Beijing 100730, China
| | - Yarong Song
- Department of Microbiology & Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China
| | - Yiwei Xiao
- Department of Microbiology & Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China
| | - Tong Wang
- Department of Clinical Laboratory, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
| | - Lili Li
- Department of Microbiology & Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China
| | - Minmin Liu
- Department of Microbiology & Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China
| | - Jie Li
- Department of Microbiology & Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China
| | - Jie Wang
- Department of Microbiology & Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China
- NHC Key Laboratory of Medical Immunology, Peking University, Beijing 100191, China
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Liu H, Chen S, Liu X, Lou J. Effect of S-region mutations on HBsAg in HBsAg-negative HBV-infected patients. Virol J 2024; 21:92. [PMID: 38654327 PMCID: PMC11040738 DOI: 10.1186/s12985-024-02366-2] [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: 02/25/2024] [Accepted: 04/15/2024] [Indexed: 04/25/2024] Open
Abstract
BACKGROUND Occult HBV infection (OBI) is a special form of hepatitis B virus (HBV) infection that may cause Liver cirrhosis and hepatocellular carcinoma, causing significant harm to patients. Given the insidious nature of OBI, it is usually not easy to be detected. Most of the samples currently studied are concentrated on blood donors, however, patients in this special state have not been fully studied. This project aimed to study the effect of HBV S region mutations on HBsAg in patients with clinical OBI. METHODS Collect 107 HBsAg-/HBV DNA + blood samples from Beijing Youan Hospital, Capital Medical University from August 2022 to April 2023. Next, the successfully extracted and amplified HBV DNA S regions were sequenced. Construct mutant plasmids to verify the cell function of the high-frequency mutation sites and explore the possible molecular mechanism. RESULTS Sixty-eight HBsAg-negative samples were sequenced, revealing high-frequency amino acid substitution sites in the HBV S protein, including immune escape mutations (i.e., sY100C、sK122R、sI126T、sT131P、and sS114T) and TMD (Transmembrane domain) region substitutions (i.e., sT5A、sG10D、sF20S、and sS3N). We constructed a portion of the mutant plasmids and found that sT5A, sF20S, sG10D, sS3N, sI68T, and sI126T single point mutations or combined mutations may decrease HBsAg expression or change the antigenicity of HBsAg leading to detection failure. CONCLUSIONS HBsAg-negative patients may show various mutations and amino acid replacement sites at high frequency in the HBV S-region, and these mutations may lead to undetectable Hepatitis B surface antigen (HBsAg), HBsAg antigenic changes or secretion inhibition.
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Affiliation(s)
- Hui Liu
- Clinical Laboratory Center, Beijing Youan Hospital, Capital Medical University, 100069, Beijing, China
| | - Shuxiang Chen
- Clinical Laboratory Center, Beijing Youan Hospital, Capital Medical University, 100069, Beijing, China
| | - Xin Liu
- Clinical Laboratory Center, Beijing Youan Hospital, Capital Medical University, 100069, Beijing, China
| | - Jinli Lou
- Clinical Laboratory Center, Beijing Youan Hospital, Capital Medical University, 100069, Beijing, China.
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Ou G, Qing L, Zhang L, Yang Y, Ye G, Peng L, Li Y, Yang L, Liu Y. Cytokine IL-5 and HGF: combined prediction of non-/low immune response to hepatitis B vaccination at birth in infants born to HBsAg-positive mothers. Front Cell Infect Microbiol 2024; 14:1332666. [PMID: 38495649 PMCID: PMC10940320 DOI: 10.3389/fcimb.2024.1332666] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2023] [Accepted: 02/19/2024] [Indexed: 03/19/2024] Open
Abstract
Background The immune response to hepatitis B vaccine may be influenced by numerous factors, and patients with non/low response re-exposed to hepatitis B virus remain susceptible. Thus, a better understanding of the underlying mechanisms of non/low immune response in infants born to Hepatitis B surface antigen (HBsAg)-positive mothers is essential. Methods 100 infants born to HBsAg-positive mothers from 2015 to 2020 were enrolled in the study, further divided into the non/low response group (n=13) and the moderate strong response group (n=87) based on the quantification of hepatitis B surface antibody at 12 months of age. The differential expression of 48 immune-related cytokines in the two groups was compared and analyzed in detail. The key cytokines were further identified and clinically predictive models were developed. Results We found that 13 cytokines were lowly expressed and one cytokine was highly expressed in the non/low response group, compared with the moderate strong response group at birth. In addition, 9 cytokines were lowly expressed and one cytokine was highly expressed in the non/low response group at 12 months of age. Furthermore, we found that IL-5 and HGF were promising predictors for predicting the immunization response to hepatitis B vaccine in infants, and the combination of the two cytokines showed the best predictive efficiency, with an area under the curve (AUC) value of 0.844. Conclusion The present study provides a theoretical basis on cytokines for developing and implementing effective immunotherapies against non/low immune response in infants born to HBsAg-positive mothers.
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Affiliation(s)
- Guanyong Ou
- National Clinical Research Center for Infectious Disease, State Key Discipline of Infectious Disease, The Third People’s Hospital of Shenzhen, Second Hospital Affiliated to Southern University of Science and Technology, Shenzhen, China
- School of Medicine, Southern University of Science and Technology, Shenzhen, China
| | - Ling Qing
- National Clinical Research Center for Infectious Disease, State Key Discipline of Infectious Disease, The Third People’s Hospital of Shenzhen, Second Hospital Affiliated to Southern University of Science and Technology, Shenzhen, China
- Graduate Collaborative Training Base of Shenzhen Third People’s Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan, China
| | - Li Zhang
- National Clinical Research Center for Infectious Disease, State Key Discipline of Infectious Disease, The Third People’s Hospital of Shenzhen, Second Hospital Affiliated to Southern University of Science and Technology, Shenzhen, China
- Graduate Collaborative Training Base of Shenzhen Third People’s Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan, China
| | - Yang Yang
- National Clinical Research Center for Infectious Disease, State Key Discipline of Infectious Disease, The Third People’s Hospital of Shenzhen, Second Hospital Affiliated to Southern University of Science and Technology, Shenzhen, China
| | - Guoguo Ye
- National Clinical Research Center for Infectious Disease, State Key Discipline of Infectious Disease, The Third People’s Hospital of Shenzhen, Second Hospital Affiliated to Southern University of Science and Technology, Shenzhen, China
| | - Ling Peng
- National Clinical Research Center for Infectious Disease, State Key Discipline of Infectious Disease, The Third People’s Hospital of Shenzhen, Second Hospital Affiliated to Southern University of Science and Technology, Shenzhen, China
| | - Yanjie Li
- National Clinical Research Center for Infectious Disease, State Key Discipline of Infectious Disease, The Third People’s Hospital of Shenzhen, Second Hospital Affiliated to Southern University of Science and Technology, Shenzhen, China
| | - Liuqing Yang
- National Clinical Research Center for Infectious Disease, State Key Discipline of Infectious Disease, The Third People’s Hospital of Shenzhen, Second Hospital Affiliated to Southern University of Science and Technology, Shenzhen, China
| | - Yingxia Liu
- National Clinical Research Center for Infectious Disease, State Key Discipline of Infectious Disease, The Third People’s Hospital of Shenzhen, Second Hospital Affiliated to Southern University of Science and Technology, Shenzhen, China
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Wu J, He J, Xu H. Global prevalence of occult HBV infection in children and adolescents: A systematic review and meta-analysis. Ann Hepatol 2024; 29:101158. [PMID: 37748752 DOI: 10.1016/j.aohep.2023.101158] [Citation(s) in RCA: 6] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/28/2023] [Revised: 08/17/2023] [Accepted: 09/11/2023] [Indexed: 09/27/2023]
Abstract
INTRODUCTION AND OBJECTIVES Occult HBV infection (OBI) is a specific form of hepatitis B virus (HBV) infection and has the possibility of developing into hepatocellular carcinoma (HCC) in adults. This study aimed to estimate the global prevalence of occult HBV infection in children and adolescents. MATERIALS AND METHODS We systematically searched PubMed, Embase, Web of Science, and Cochrane databases for relevant studies on the prevalence of OBI in children and adolescents. Meta-analysis was performed using STATA 16 software. RESULTS Fifty studies were included. The overall prevalence of OBI in children and adolescents was 7.5% (95% CI: 0.050-0.103). In different risk populations, OBI prevalence was remarkably high in the HIV-infected population (24.2%, 95% CI: 0.000-0.788). The OBI prevalence was 0.8% (95% CI:0.000-0.029) in the healthy population, 3.8% (95% CI:0.012-0.074) in the general population, and 6.4% (95% CI: 0.021-0.124) in children born to HBsAg-positive mothers. Based on different serological profiles, the prevalence of OBI in HBsAg-negative and anti-HBc-positive patients was 6.6% (95% CI: 0.016-0.136), 3.0% (95% CI: 0.009-0.059) in HBsAg-negative and anti-HBc-negative patients, 4.6% (95% CI: 0.015-0.088) in HBsAg-negative and anti-HBs-positive patients, and 3.7% (95% CI: 0.001-0.102) in HBsAg-negative and anti-HBs-negative patients. CONCLUSIONS Despite HBV vaccination and hepatitis B immunoglobulin (HBIG), OBI is common in children and adolescents in high-risk groups.
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Affiliation(s)
- Jiaying Wu
- Department of Infectious Diseases, Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Child Infection and Immunity, Chongqing, China; The First batch of key Disciplines On Public Health in Chongqing, Health Commission of Chongqing, Chongqing, China
| | - Jiayao He
- Affiliated Hospital of Chengdu University, Chengdu, China
| | - Hongmei Xu
- Department of Infectious Diseases, Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Child Infection and Immunity, Chongqing, China; The First batch of key Disciplines On Public Health in Chongqing, Health Commission of Chongqing, Chongqing, China.
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Post-Vaccination and Post-Infection Immunity to the Hepatitis B Virus and Circulation of Immune-Escape Variants in the Russian Federation 20 Years after the Start of Mass Vaccination. Vaccines (Basel) 2023; 11:vaccines11020430. [PMID: 36851307 PMCID: PMC9962567 DOI: 10.3390/vaccines11020430] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2022] [Revised: 02/07/2023] [Accepted: 02/09/2023] [Indexed: 02/16/2023] Open
Abstract
A neonatal vaccination against the Hepatitis B virus (HBV) infection was initiated in Russia 20 years ago, with catch-up immunization for adolescents and adults under the age of 60 years launched in 2006. Here, we have assessed the humoral immunity to HBV in different regions of Russia, as well as the infection frequency following 20 years of a nationwide vaccination campaign. We have also evaluated the role of immune-escape variants in continuing HBV circulation. A total of 36,149 healthy volunteers from nine regions spanning the Russian Federation from west to east were tested for HBV surface antigen (HBsAg), antibodies to HBV capsid protein (anti-HBc), and antibodies to HBsAg (anti-HBs). HBV sequences from 481 chronic Hepatitis B patients collected from 2018-2022 were analyzed for HBsAg immune-escape variants, compared with 205 sequences obtained prior to 2010. Overall, the HBsAg detection rate was 0.8%, with this level significantly exceeded only in one study region, the Republic of Dagestan (2.4%, p < 0.0001). Among the generation vaccinated at birth, the average HBsAg detection rate was below 0.3%, ranging from 0% to 0.7% depending on the region. The anti-HBc detection rate in subjects under 20 years was 7.4%, indicating ongoing HBV circulation. The overall proportion of participants under 20 years with vaccine-induced HBV immunity (anti-HBs positive, anti-HBc negative) was 41.7% but below 10% in the Tuva Republic and below 25% in the Sverdlovsk and Kaliningrad regions. The overall prevalence of immune-escape HBsAg variants was 25.2% in sequences obtained from 2018-2022, similar to the prevalence of 25.8% in sequences collected prior to 2010 (p > 0.05). The population dynamics of immune-escape variants predicted by Bayesian analysis have remained stable over the last 20 years, indicating the absence of vaccine-driven positive selection. In contrast, the wild-type HBV population size experienced a rapid decrease starting in the mid-1990s, following the introduction of mass immunization, but it subsequently began to recover, reaching pre-vaccination levels by 2020. Taken together, these data indicate that it is gaps in vaccination, and not virus evolution, that may be responsible for the continued virus circulation despite 20 years of mass vaccination.
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10
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Deng X, Guo X, Gu H, Wang D, Laperche S, Allain J, Zang L, Candotti D. Anti-HBc-nonreactive occult hepatitis B infections with HBV genotypes B and C in vaccinated immunocompetent adults. J Viral Hepat 2022; 29:958-967. [PMID: 35876456 PMCID: PMC9804389 DOI: 10.1111/jvh.13733] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/07/2022] [Accepted: 07/01/2022] [Indexed: 01/05/2023]
Abstract
Absence of anti-HBc reactivity with detectable anti-HBs was observed in blood donors with occult hepatitis B virus (HBV) infection (OBI). The prevalence and mechanisms underlying this uncommon condition were investigated over time in Chinese blood donors with OBI. Isolated anti-HBs OBI status was identified from 466,911 donors from Dalian, China, and monitored in follow-up (range: 2.6-84.3 months). HBV vaccination status was documented, and infecting viral strains were characterized. Of 451 confirmed OBIs (1:1035), 43 (9.5%; 1:10,858) had isolated anti-HBs as only serological marker. Isolated anti-HBs OBIs differed from anti-HBc-reactive OBIs by significantly younger age (median 24 years), higher HBV DNA (median: 20 IU/ml) and anti-HBs (median 60.5 IU/L) levels, paucity of mutations in HBV Core and S proteins, and high vaccination rate (72%). Vaccinated isolated anti-HBs OBIs (n = 31) differed from unvaccinated (n = 11) by significantly younger age (22 vs 38 years), higher anti-HBs level at index (48% vs 9% with anti-HBs >100 IU/L) and higher frequency of anti-HBs immune response (44% vs 20%). Of 15 vaccinated and 5 unvaccinated OBIs follow-up, 65% (8 vaccinated and 5 unvaccinated) became HBV DNA negative suggesting aborted recent infection, while 35% (7 vaccinated) had low persistent viraemia 2 to 65 months post index. In conclusion, isolated anti-HBs OBI in Chinese blood donors appears associated with young, vaccinated, adults exposed to HBV who predominantly develop low level aborted infection revealed by transient HBV DNA and immune anti-HBs response. However, a subset of individuals still experienced low but persistent viral replication whose clinical outcome remains uncertain.
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Affiliation(s)
| | | | - Hongfang Gu
- Dalian Public Health Clinical CenterDalianChina
| | | | - Syria Laperche
- Department of Blood Transmitted AgentsNational Institute of Blood TransfusionParisFrance
| | | | | | - Daniel Candotti
- Department of Blood Transmitted AgentsNational Institute of Blood TransfusionParisFrance,Department of VirologyHenri Mondor Hospital, AP‐HPCréteilFrance,University of Paris‐Est, INSERM U955, IMRBCréteilFrance
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11
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Jiang X, Chang L, Yan Y, Ji H, Sun H, Xiao Y, Song S, Feng K, Nuermaimaiti A, Wang L. Role of S Protein Transmembrane Domain Mutations in the Development of Occult Hepatitis B Virus Infection. Emerg Microbes Infect 2022; 11:2184-2196. [PMID: 35976035 PMCID: PMC9518280 DOI: 10.1080/22221751.2022.2114849] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
Occult HBV infection (OBI) is a special infection status during Hepatitis B virus (HBV) infection. The underlying mechanism of its occurrence remains unclear. This study conducted sequencing analysis on 104 OBI plasma samples and 524 HBsAg positive samples from 29 blood centres, and searched for high-frequency mutations in transmembrane domain (TMD) of S protein in the OBI population. Plasmids with TMD high-frequency mutations were constructed, in vivo and in vitro functional experiments were performed to investigate possible molecular mechanisms of OBI occurrence. We found 22 high-frequency TMD mutations in genotype B OBI strains. Among them, five mutations can lead to impairment of HBsAg secretion; seven mutations had accumulated intracellular HBsAg while extracellular HBsAg didn’t decrease compared to wildtype. This study chose C85R from TMD2, F220C, and F220Y from TMD4 for further exploration. Protein structure predication showed these three mutant HBsAg displayed changed hydrophilic properties and tended to accumulate in the phospholipid bilayer of cell membrane. Mutant HBsAg’s secretion disorder may induce OBI. On the other hand, V168A + V177A from TMD3 expressed increased HBsAg both in intracellular and extracellular levels. This mutation had most unstable natural conformation and may be inclined to transition into V177A or V168A + S174N + V177A. These three mutations were more prone to mixed infection, presenting a state of coexistence, thus approaching the impaired secretion pattern of OBI. This study demonstrated TMD mutations could contribute to the occurrence of OBI and provided a theoretical basis for OBI study and the functional cure of chronic hepatitis B virus infection.
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Affiliation(s)
- Xinyi Jiang
- National Center for Clinical Laboratories, Beijing Hospital, National Center of Gerontology; Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, P.R. China.,Beijing Engineering Research Center of Laboratory Medicine, Beijing Hospital, P.R. China.,Graduate School, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, P.R. China."
| | - Le Chang
- National Center for Clinical Laboratories, Beijing Hospital, National Center of Gerontology; Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, P.R. China.,Beijing Engineering Research Center of Laboratory Medicine, Beijing Hospital, P.R. China.,Graduate School, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, P.R. China."
| | - Ying Yan
- National Center for Clinical Laboratories, Beijing Hospital, National Center of Gerontology; Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, P.R. China.,Beijing Engineering Research Center of Laboratory Medicine, Beijing Hospital, P.R. China.,Graduate School, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, P.R. China."
| | - Huimin Ji
- National Center for Clinical Laboratories, Beijing Hospital, National Center of Gerontology; Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, P.R. China.,Beijing Engineering Research Center of Laboratory Medicine, Beijing Hospital, P.R. China.,Graduate School, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, P.R. China."
| | - Huizhen Sun
- National Center for Clinical Laboratories, Beijing Hospital, National Center of Gerontology; Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, P.R. China.,Beijing Engineering Research Center of Laboratory Medicine, Beijing Hospital, P.R. China.,Graduate School, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, P.R. China."
| | - Yingzi Xiao
- National Center for Clinical Laboratories, Beijing Hospital, National Center of Gerontology; Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, P.R. China.,Beijing Engineering Research Center of Laboratory Medicine, Beijing Hospital, P.R. China.,Graduate School, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, P.R. China."
| | - Shi Song
- National Center for Clinical Laboratories, Beijing Hospital, National Center of Gerontology; Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, P.R. China.,Beijing Engineering Research Center of Laboratory Medicine, Beijing Hospital, P.R. China.,Graduate School, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, P.R. China."
| | - Kaihao Feng
- National Center for Clinical Laboratories, Beijing Hospital, National Center of Gerontology; Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, P.R. China.,Beijing Engineering Research Center of Laboratory Medicine, Beijing Hospital, P.R. China.,Graduate School, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, P.R. China."
| | - Abudulimutailipu Nuermaimaiti
- National Center for Clinical Laboratories, Beijing Hospital, National Center of Gerontology; Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, P.R. China.,Beijing Engineering Research Center of Laboratory Medicine, Beijing Hospital, P.R. China.,Graduate School, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, P.R. China."
| | - Lunan Wang
- National Center for Clinical Laboratories, Beijing Hospital, National Center of Gerontology; Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, P.R. China.,Beijing Engineering Research Center of Laboratory Medicine, Beijing Hospital, P.R. China.,Graduate School, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, P.R. China."
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12
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Li AY, Liu Z, Song Y, Xiao Y, Jiang J, Li L, Zhai X, Liu J, Duan Z, Ding F, Liu J, Zhuang H, Zhu L, Jiang J, Zou H, Wang J, Li J. Reduction of the occurrence of occult HBV infection in infants by increasing the dose of hepatitis B vaccine: a large prospective cohort study. Emerg Microbes Infect 2021; 9:1881-1891. [PMID: 32779526 PMCID: PMC7473118 DOI: 10.1080/22221751.2020.1808533] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Occult hepatitis B virus (HBV) infection (OBI) has been observed among infants born to hepatitis B surface antigen (HBsAg)-positive mothers despite successful immunoprophylaxis. This study enrolled 549 infants [349 infants received a 10μg/dose of hepatitis B vaccine (HepB), and 200 infants received 20μg/dose HepB] born to HBsAg-positive mothers with HBV DNA load >6log10IU/mL. The anti-HBs levels in the 10μg group were significantly lower than that in the 20μg group both at 7 [652.48 (564.05-754.82) vs. 1541.72 (1268.69-1873.51) mIU/mL, P<0.001] and 12 months old [257.44 (220.29-300.88) vs. 1073.41 (839.27-1372.78) mIU/mL, P<0.001]. The OBI incidence in the 10μg group was significantly higher than that in the 20μg group at both 7 [21.55% (25/116) vs. 7.56% (9/119), P=0.002] and 12 months old [17.07% (14/82) vs. 6.90% (6/87), P=0.041]. OBI incidence in infants with anti-HBs levels <100mIU/mL was higher than that of those with anti-HBs ≥100mIU/mL [35.71% (5/14) vs. 13.12% (29/221), P=0.036]. This study showed that increasing the immunisation dose from 10μg to 20μg significantly improved anti-HBs levels and decreased OBI incidence in infants with a high maternal viral load. We recommend 20μg HepB to treat this high-risk population.
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Affiliation(s)
- Authors Yi Li
- Department of Microbiology & Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, People's Republic of China
| | - Zhixiu Liu
- Department of Microbiology & Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, People's Republic of China
| | - Yarong Song
- Department of Microbiology & Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, People's Republic of China
| | - Yiwei Xiao
- Department of Microbiology & Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, People's Republic of China
| | - Jing Jiang
- Department of Clinical Research, First Hospital of Jilin University, Changchun, People's Republic of China
| | - Lili Li
- Department of Microbiology & Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, People's Republic of China
| | - Xiangjun Zhai
- Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, People's Republic of China
| | - Jianxun Liu
- Zhengzhou Municipal Center for Disease Control and Prevention, Zhengzhou, People's Republic of China
| | - Zhongping Duan
- Beijing Youan Hospital, Capital Medical University, Beijing, People's Republic of China
| | - Feng Ding
- Department of Microbiology & Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, People's Republic of China
| | - Jia Liu
- Department of Microbiology & Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, People's Republic of China
| | - Hui Zhuang
- Department of Microbiology & Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, People's Republic of China
| | - Liguo Zhu
- Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, People's Republic of China
| | - Jie Jiang
- Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, People's Republic of China
| | - Huaibin Zou
- Beijing Youan Hospital, Capital Medical University, Beijing, People's Republic of China
| | - Jie Wang
- Department of Microbiology & Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, People's Republic of China
| | - Jie Li
- Department of Microbiology & Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, People's Republic of China
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13
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Hu AQ, Cai QY, Zhang M, Liu HY, Wang TL, Han WH, Li Q, Fan W, Li YJ, He YN, Zheng YJ. Overt and occult hepatitis B infection after neonatal vaccination: mother-to-infant transmission and HBV vaccine effectiveness. Int J Infect Dis 2021; 104:601-609. [PMID: 33508476 DOI: 10.1016/j.ijid.2021.01.045] [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: 06/15/2020] [Revised: 12/28/2020] [Accepted: 01/19/2021] [Indexed: 11/28/2022] Open
Abstract
OBJECTIVES Overt and occult hepatitis B infection (HBI) among mothers and infants were investigated, and the effectiveness of vaccination against HBI was evaluated based on transmission types. METHODS A hospital-based cohort was built with 2,734 mothers and 330 mother-infant pairs. Their demographic data were collected. Serological HBV markers, nested-PCR for HBV genes, viral load detection, and phylogenetic analysis were done. RESULTS The overall prevalence of HBI among mothers was 12.1% (330/2,734), with 10.4% for the overt type and 1.8% for the occult type. In 330 out of 1,650 (20%) mother-infant pairs, the overall, type-I (from overt mother to overt infant), type-II (from overt mother to occult infant), and type-Ⅲ (from occult mother to occult infant) transmissions were 1.9% (1/54), 5.6% (3/54) and 0.0% (0/7). The refinement of HBI classification improved the estimate of vaccine effectiveness against HBI from 74.4%-80.9% to 94.4%, which was more prominent for type-II. One mother-infant pair with type-II transmission shared nearly identical complete sequences. However, the high rate of lost-to-follow-up could not be ignored. CONCLUSIONS During the transition period, HBV is mainly transmitted from the overt type of HBI mother to infant. Intensive prenatal screening for mothers is vital.
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Affiliation(s)
- An-Qun Hu
- Department of Clinical Laboratory, Anqing Municipal Hospital, Anqing 246003, China
| | - Qian-Ying Cai
- Department of Epidemiology, School of Public Health, Fudan University, No.130 Dong'an Road, Xuhui District, Shanghai 200032, China; Key Laboratory for Health Technology Assessment, National Commission of Health and Family Planning, Fudan University, No.130 Dong'an Road, Xuhui District, Shanghai 200032, China; Key Laboratory of Public Health Safety, Ministry of Education, School of Public Health, Fudan University, Shanghai 200233, China; Institute of Microsurgery on Extremities, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China
| | - Miao Zhang
- Department of Epidemiology, School of Public Health, Fudan University, No.130 Dong'an Road, Xuhui District, Shanghai 200032, China; Key Laboratory for Health Technology Assessment, National Commission of Health and Family Planning, Fudan University, No.130 Dong'an Road, Xuhui District, Shanghai 200032, China; Key Laboratory of Public Health Safety, Ministry of Education, School of Public Health, Fudan University, Shanghai 200233, China
| | - Hai-Yan Liu
- Department of Clinical Laboratory, Anqing Municipal Hospital, Anqing 246003, China
| | - Tian-Lei Wang
- Department of Epidemiology, School of Public Health, Fudan University, No.130 Dong'an Road, Xuhui District, Shanghai 200032, China; Key Laboratory for Health Technology Assessment, National Commission of Health and Family Planning, Fudan University, No.130 Dong'an Road, Xuhui District, Shanghai 200032, China; Key Laboratory of Public Health Safety, Ministry of Education, School of Public Health, Fudan University, Shanghai 200233, China
| | - Wen-Hui Han
- Department of Obstetrics and Gynecology, Anqing Municipal Hospital, Anqing 246003, China
| | - Qing Li
- Department of Obstetrics and Gynecology, Anqing Municipal Hospital, Anqing 246003, China
| | - Wei Fan
- Department of Epidemiology, School of Public Health, Fudan University, No.130 Dong'an Road, Xuhui District, Shanghai 200032, China; Key Laboratory for Health Technology Assessment, National Commission of Health and Family Planning, Fudan University, No.130 Dong'an Road, Xuhui District, Shanghai 200032, China; Key Laboratory of Public Health Safety, Ministry of Education, School of Public Health, Fudan University, Shanghai 200233, China
| | - Yi-Jie Li
- Department of Epidemiology, School of Public Health, Fudan University, No.130 Dong'an Road, Xuhui District, Shanghai 200032, China; Key Laboratory for Health Technology Assessment, National Commission of Health and Family Planning, Fudan University, No.130 Dong'an Road, Xuhui District, Shanghai 200032, China; Key Laboratory of Public Health Safety, Ministry of Education, School of Public Health, Fudan University, Shanghai 200233, China
| | - Yi-Ning He
- Department of Epidemiology, School of Public Health, Fudan University, No.130 Dong'an Road, Xuhui District, Shanghai 200032, China; Key Laboratory for Health Technology Assessment, National Commission of Health and Family Planning, Fudan University, No.130 Dong'an Road, Xuhui District, Shanghai 200032, China; Key Laboratory of Public Health Safety, Ministry of Education, School of Public Health, Fudan University, Shanghai 200233, China
| | - Ying-Jie Zheng
- Department of Epidemiology, School of Public Health, Fudan University, No.130 Dong'an Road, Xuhui District, Shanghai 200032, China; Key Laboratory for Health Technology Assessment, National Commission of Health and Family Planning, Fudan University, No.130 Dong'an Road, Xuhui District, Shanghai 200032, China; Key Laboratory of Public Health Safety, Ministry of Education, School of Public Health, Fudan University, Shanghai 200233, China.
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14
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Ghaziasadi A, Fakhari Z, Aghcheli B, Poortahmasebi V, Farahmand M, Norouzi M, Ghalichi L, Soleimani A, Hedayat Yaghoobi M, Ravanshad M, Jazayeri SM. High prevalence of occult hepatitis B infection (OBI) among healthy children and their parents in Alborz province, Iran; Vertical OBI, myth or truth? Liver Int 2020; 40:92-100. [PMID: 31518482 DOI: 10.1111/liv.14252] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/25/2019] [Revised: 08/23/2019] [Accepted: 08/30/2019] [Indexed: 12/13/2022]
Abstract
BACKGROUND Occult hepatitis B infection (OBI) has been described in various clinical settings including after hepatitis B virus (HBV) immunization. The purpose of study was to characterize the prevalence of OBI among immunized children from a subset of general population and the parents of OBI-positive cases. METHODS Sera of 1200 children from general population who have been previously immunized by HBV vaccine were assayed for anti-HBs. 660 were randomly selected for HBV DNA testing by different polymerase chain reaction (PCR) methods and were analysed by direct sequencing on surface genes. RESULTS None of participants were positive for HBsAg and anti-HBc. 549 (45.7%) and 651 (54.3%) cases had anti-HBs > 10 mIU/mL (responders) and < 10 mIU/mL (nonresponders) respectively. Of 660 selected specimens, 91 (16%) of children were positive for OBI. 23 (25.2%) and 68 (74.8%) of HBV DNA positive cases were belonged to responders and nonresponders, respectively, showing significant difference (P < .001). The mean levels of anti-HBs in OBI-positive and OBI-negative groups, showed no considerable variations. The mean viral load for OBI-positive cases showed substantial differences between responders and nonresponders (P = .007). Of 49 parents (98 individuals) of OBI-positive children 11 (22%) and 18 (36%) were positive for anti-HBc and anti-HBs respectively. Molecular testing was positive in 32 subjects (16 couples, 32.6%). In total, 6 mothers and 11 fathers were positive for OBI. CONCLUSION A proportion of OBI-positive vaccinated children could be existed in different populations. This finding could be arisen from vertical HBV transmission or vertical OBI possibly from their parents.
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Affiliation(s)
- Azam Ghaziasadi
- Department of Virology, School of Public Health, Tehran University of Medical Sciences Tehran, Tehran, Iran
| | - Zahra Fakhari
- Department of Virology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
| | - Bahman Aghcheli
- Department of Virology, School of Public Health, Tehran University of Medical Sciences Tehran, Tehran, Iran
| | - Vahdat Poortahmasebi
- Infectious and Tropical Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
- Liver and Gastrointestinal Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
- Research Center for Clinical Virology, Tehran University of Medical Sciences, Tehran, Iran
| | - Mohammad Farahmand
- Department of Virology, School of Public Health, Tehran University of Medical Sciences Tehran, Tehran, Iran
| | - Mehdi Norouzi
- Department of Virology, School of Public Health, Tehran University of Medical Sciences Tehran, Tehran, Iran
- Research Center for Clinical Virology, Tehran University of Medical Sciences, Tehran, Iran
| | - Leila Ghalichi
- Mental Health Research Center, Psychosocial Health Research Institute, Iran University of Medical Sciences Tehran, Tehran, Iran
| | - Alireza Soleimani
- Department of Infectious Disease, Imam Ali Hospital, Alborz University of Medical Sciences, Karaj, Iran
| | - Mojtaba Hedayat Yaghoobi
- Department of Infectious Disease, Imam Ali Hospital, Alborz University of Medical Sciences, Karaj, Iran
| | - Mehrdad Ravanshad
- Department of Virology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
| | - Seyed Mohammad Jazayeri
- Department of Virology, School of Public Health, Tehran University of Medical Sciences Tehran, Tehran, Iran
- Research Center for Clinical Virology, Tehran University of Medical Sciences, Tehran, Iran
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15
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Raimondo G, Locarnini S, Pollicino T, Levrero M, Zoulim F, Lok AS. Update of the statements on biology and clinical impact of occult hepatitis B virus infection. J Hepatol 2019; 71:397-408. [PMID: 31004683 DOI: 10.1016/j.jhep.2019.03.034] [Citation(s) in RCA: 343] [Impact Index Per Article: 57.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/21/2019] [Revised: 03/20/2019] [Accepted: 03/28/2019] [Indexed: 02/06/2023]
Abstract
In October 2018 a large number of international experts with complementary expertise came together in Taormina to participate in a workshop on occult hepatitis B virus infection (OBI). The objectives of the workshop were to review the existing knowledge on OBI, to identify issues that require further investigation, to highlight both existing controversies and newly emerging perspectives, and ultimately to update the statements previously agreed in 2008. This paper represents the output from the workshop.
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Affiliation(s)
- Giovanni Raimondo
- Division of Clinical and Molecular Hepatology, University of Messina, Messina, Italy; Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy.
| | - Stephen Locarnini
- Victorian Infectious Diseases Reference Laboratory at the Doherty Institute, Melbourne, Victoria, Australia
| | - Teresa Pollicino
- Division of Clinical and Molecular Hepatology, University of Messina, Messina, Italy; Department of Human Pathology, University of Messina, Messina, Italy
| | - Massimo Levrero
- Cancer Research Center of Lyon, INSERM U1052, Hospices Civils de Lyon, Lyon University, Lyon, France
| | - Fabien Zoulim
- Cancer Research Center of Lyon, INSERM U1052, Hospices Civils de Lyon, Lyon University, Lyon, France
| | - Anna S Lok
- Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, MI, USA
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16
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Hung WL, Wu JF, Ni YH, Chen HL, Chiang CL, Chang MH, Hsu HY. Occult hepatitis B virus and surface antigen mutant infection in healthy vaccinated cohorts and children with various forms of hepatitis and multiple transfusions. Liver Int 2019; 39:1052-1061. [PMID: 30790411 DOI: 10.1111/liv.14076] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/31/2018] [Revised: 01/29/2019] [Accepted: 02/01/2019] [Indexed: 12/15/2022]
Abstract
BACKGROUND AND AIMS Despite the success of universal infant immunization initiated in Taiwan in 1984, occult hepatitis B virus infection (OBI) and circulating surface antigen mutants remain potential obstacles for eventual eradication of HBV infection. METHODS From 3299 apparently healthy, neonatally-vaccinated subjects (<30 years of age ) enrolled during 2014 serosurvey, we recruited all HBsAg-positive (n = 17), all HBsAg-negative but anti-HBc-positive (n = 132) and randomly selected HBsAg-negative and anti-HBc-negative subjects (n = 411). These recruited subjects and 81 HBsAg-negative children with various forms of hepatitis and multiple transfusions were analysed for serum HBV DNA. RESULTS In healthy, HBsAg-negative subjects, OBI frequency was higher in anti-HBc-positive than anti-HBc-negative individuals (8/90[8.9%] vs 8/301[2.7%], P = 0.0192) aged <18-years, but was not different between anti-HBc-positive and anti-HBc-negative individuals (0/11[0%] vs 3/110[2.7%], P > 0.05) aged 18 to 30 years. OBI occurred more frequently in children of HBsAg-positive mothers than in children of HBsAg-negative mothers (10/101 [9.9%] vs 1/75 [1.3%], P = 0.025). The prevalence of surface 'a' determinant (aa110-160) mutants was 13.3% (2/15) in OBI subjects compared to 36.4% (4/11) in HBsAg-positive subjects (P > 0.05). OBI was found in 30% (3/10) of serologic 'non-A to E' viral hepatitis, 14.3% (3/21) of chronic hepatitis C and 2.0% (1/50) of multitransfused, thalassemic children. CONCLUSIONS In this highly immunized population, surface antigen mutant infection is uncommon and has low contribution to OBI development. HBsAg screening plus highly sensitive HBV DNA assays are needed for assurance of blood supply safety. Multiple transfusions from HBsAg-negative blood donors rarely result in persistent HBV infection. HBV might be related to some of serologic 'non-A to E' viral hepatitis.
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Affiliation(s)
- Wei-Li Hung
- Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan
| | - Jia-Feng Wu
- Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan
| | - Yen-Hsuan Ni
- Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan
| | - Huey-Ling Chen
- Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan.,Graduate Institute of Medical Education and Bioethics, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Cheng-Lun Chiang
- Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan.,Graduate Institute of Medical Education and Bioethics, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Mei-Hwei Chang
- Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan
| | - Hong-Yuan Hsu
- Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan.,Graduate Institute of Medical Education and Bioethics, College of Medicine, National Taiwan University, Taipei, Taiwan
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Eilard A, Andersson M, Ringlander J, Wejstål R, Norkrans G, Lindh M. Vertically acquired occult hepatitis B virus infection may become overt after several years. J Infect 2019; 78:226-231. [PMID: 30658081 DOI: 10.1016/j.jinf.2019.01.002] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2018] [Revised: 12/19/2018] [Accepted: 01/07/2019] [Indexed: 01/16/2023]
Abstract
OBJECTIVES To study the frequency of vertically acquired occult hepatitis B virus (HBV) infection (OBI). METHODS We investigated 44 children born to hepatitis B surface antigen (HBsAg) positive mothers. They received HBV vaccine directly after birth and at 2, 6 and 52 weeks of age; eight with HBeAg-positive mothers also received hepatitis B immunoglobulin (HBIG). HBV DNA was analyzed in blood collected at 6 weeks and 12 months of age, and HBV antibodies at 12 and 18 months of age. RESULTS HBV DNA, but not HBsAg or anti-HBc, was detected at 12 months of age in three children. The viral sequences were almost identical with HBV DNA from their mothers who all were HBeAg-positive and had received tenofovir during pregnancy. Follow-up at 5-7 years age showed that one of the three children had become seropositive for HBsAg and anti-HBc. This child and one of the other two had detectable HBV DNA at the follow-up, with whole genome sequences identical to those in HBV from their mothers. CONCLUSIONS Mothers-to-child transmission of HBV can, despite adequate prophylaxis, lead to OBI which may later develop into overt HBV infection. Whether such infections are of clinical importance needs to be further investigated.
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Affiliation(s)
- Anders Eilard
- Department of Infectious Diseases, University of Gothenburg, 413 46 Gothenburg, Sweden.
| | - Maria Andersson
- Department of Infectious Diseases, University of Gothenburg, 413 46 Gothenburg, Sweden
| | - Johan Ringlander
- Department of Infectious Diseases, University of Gothenburg, 413 46 Gothenburg, Sweden
| | - Rune Wejstål
- Department of Infectious Diseases, University of Gothenburg, 413 46 Gothenburg, Sweden
| | - Gunnar Norkrans
- Department of Infectious Diseases, University of Gothenburg, 413 46 Gothenburg, Sweden
| | - Magnus Lindh
- Department of Infectious Diseases, University of Gothenburg, 413 46 Gothenburg, Sweden.
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