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Tang Q, Wang C, Li H, Chen Z, Zhang L, Zhang J, Liu X, Xue Y, Qiu Y, Peng M, Zeng Y, Hu P. Unexpected HBsAg decrease after nucleoside analogues retreatment among HBeAg positive postpartum women: a pilot study. Virol J 2025; 22:36. [PMID: 39948654 PMCID: PMC11827179 DOI: 10.1186/s12985-025-02632-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2024] [Accepted: 01/14/2025] [Indexed: 02/16/2025] Open
Abstract
BACKGROUND Mother-to-child transmission (MTCT) is one of the main routes of transmission of HBV, and previous studies focused on the efficacy and safety of nucleoside analogues (NAs) in preventing MTCT. There are limited data on virologic changes of chronic hepatitis B (CHB) patients after discontinuing treatment postpartum and the efficacy of retreatment. METHODS A retrospective-prospective real-world pilot cohort study on pregnant women with CHB was conducted. Biochemical and virological characteristics (HBsAg, HBeAg and HBV DNA) in patients received NAs treatment pre-pregnancy (n = 24), patients discontinued treatment after delivery (n = 88) and retreatment patients (n = 22) were collected during follow-up. RESULTS The incidences of HBeAg clearance, half decrease of HBsAg, 0.5 lg decrease of HBsAg and HBsAg < 1000 IU/mL in patients discontinuing treatment postpartum were 5.7% (4/70), 10.0% (8/48), 6.3% (3/48) and 1.6% (1/61), respectively. More significantly decreases of HBsAg, HBeAg and HBV DNA were observed in retreatment patients compared to patients received NAs treatment pre-pregnancy. Significantly higher cumulative incidences of half decrease of HBsAg, 0.5 lg decrease of HBsAg and HBsAg < 1000 IU/mL were achieved in retreatment patients compared to patients received NAs treatment pre-pregnancy. Long-term follow-up results indicated that it is safe for HBeAg positive pregnant patients to discontinue treatment after delivery. CONCLUSION HBeAg positive patients received NAs treatment during pregnancy and discontinued it postpartum can benefit from NAs retreatment because of unexpected decrease of HBsAg, which may be helpful for achieve the goal of functional cure. Trial registration number ClinicalTrials.gov (No.ChiCTR2100054116).
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Affiliation(s)
- Qiao Tang
- Department of Infectious Diseases, Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, the Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
| | - Chunrui Wang
- Department of Infectious Diseases, Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, the Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
| | - Hu Li
- Department of Infectious Diseases, Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, the Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
| | - Zhiwei Chen
- Department of Infectious Diseases, Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, the Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
| | - Li Zhang
- Department of Infectious Diseases, Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, the Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
| | - Jing Zhang
- Department of Infectious Diseases, Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, the Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
| | - Xiaoqing Liu
- Department of Infectious Diseases, Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, the Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
| | - Yunling Xue
- Department of Infectious Diseases, Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, the Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
| | - Yue Qiu
- Department of Infectious Diseases, Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, the Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
| | - Mingli Peng
- Department of Infectious Diseases, Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, the Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
| | - Yi Zeng
- Department of Infectious Diseases, Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, the Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
| | - Peng Hu
- Department of Infectious Diseases, Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, the Second Affiliated Hospital, Chongqing Medical University, Chongqing, China.
- Department of Infectious Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
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Tang Q, Wang C, Li H, Chen Z, Liu X, Xue Y, Qiu Y, Zeng Y, Hu P. PgRNA closely correlates to cytokine profile in HBeAg-positive pregnant women undergoing prophylactic antiviral intervention. Front Immunol 2024; 15:1511855. [PMID: 39720709 PMCID: PMC11668345 DOI: 10.3389/fimmu.2024.1511855] [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: 10/15/2024] [Accepted: 11/29/2024] [Indexed: 12/26/2024] Open
Abstract
Background Previous studies primarily focused on the effects of ALT and virology, but there is a lack of research on the correlations of HBcrAg and pgRNA, two novel virologic markers, with immunological parameters in pregnant women with CHB undergoing prophylactic antiviral intervention. Methods We conducted a retrospective cohort study involving 28 HBeAg-positive pregnant women with CHB undergoing prophylactic antiviral intervention. Clinical data, virological markers (HBV DNA, HBsAg, HBeAg, HBcrAg and pgRNA) and 28 cytokines were detected at three time points: 24-28 weeks gestation (before prophylactic antiviral intervention), near birth and within 3 months postpartum. Results PgRNA was moderately (correlation coefficient between 0.4 and 0.6) positively correlated with Th1-type cytokines (IFN-γ, IL12p70, IL2, and TNF-α), Th17-type cytokines (IL21), Th2-type cytokines (IL10, IL4, and IL5), and cytokines regulating cell proliferation and differentiation (CTLA4, IL15, IL23, and TGF-β1) and moderately negatively correlated with EGF (correlation coefficient = -0.4), while ALT, HBV-DNA, HBsAg and HBcrAg were insignificantly correlated with cytokines at 24-28 weeks of gestation. Most cytokines tended to be elevated, with statistically significant increases observed only for the chemokines IP10 and MCP-1 during pregnancy. Most cytokines were significantly increased in postpartum women with virologic rebound after treatment discontinuation postpartum, but no significant change in the Th1/Th2 ratio. Changes in virologic markers were significantly correlated with cytokines. Immune activation was more pronounced in postpartum women who developed ALT flare compared to who did not, with Th1-type cytokines (especially IL12p40) and chemokines being main differential cytokines. Conclusion PgRNA was more closely correlated with cytokine profiles, and postpartum ALT flare may be the result of the interaction between Th1-type cytokines and chemokines.
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Affiliation(s)
- Qiao Tang
- The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Chunrui Wang
- The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Hu Li
- The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Zhiwei Chen
- The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Xiaoqing Liu
- The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Yunling Xue
- The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Yue Qiu
- The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Yi Zeng
- The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Peng Hu
- Department of Infectious Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
- Institute for Viral Hepatitis, The Key Laboratory of Molecular Biology for Infectious Diseases, Chinese Ministry of Education, Chongqing Medical University, Chongqing, China
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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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Gao F, Li X, Wang H, Xu Z, Qian W, Bai G. Single-cell profiling of the peripheral blood immune landscape during mid- and late-stage pregnancy. Physiol Genomics 2024; 56:855-868. [PMID: 39555960 DOI: 10.1152/physiolgenomics.00041.2024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2024] [Revised: 09/16/2024] [Accepted: 09/17/2024] [Indexed: 11/19/2024] Open
Abstract
We aimed to determine the peripheral blood mononuclear cell (PBMC) immune profiles of mid- and late-stage pregnant women to establish a foundation for studying pregnancy-related diseases. Peripheral blood samples were collected from three women each during mid- and late-stage pregnancy, and PBMCs were extracted for single-cell RNA sequencing (scRNA-seq). Peripheral blood samples were also collected for flow cytometry analysis to validate the analytical results. HOPX+ CD4+ T cells, ZNF683+CD8+ T cells, and KLRB1+CD8+ T cells significantly differed in quantitative ratio and gene transcript level between women at mid- and late-stage pregnancy. In late pregnancy, cell-to-cell communication was enhanced and effector CD8+ T cells highly expressed infection-related pathways. A rare T cell subtype, "XIST+ T cells," exhibited high XIST expression, a gene that may be involved in the regulation of immune-related gene transcription and translation, and insulin signaling pathway, during pregnancy. Monocytes exhibited significant proinflammatory and metabolic properties in mid- and late-stage pregnancy, respectively. Natural killer (NK) cells were mainly involved in T- and B-cell-mediated signaling pathways, and in T cell differentiation, in mid-pregnancy. Enhanced innate immunity of NK cells was observed. Moreover, NK cells expressed genes associated with diabetes-related pathways in late-stage pregnancy. To conclude, we present detailed changes in the immune response occurring in pregnant women from mid- to late-stage gestation, revealing significant differences in PBMC subtypes and molecular properties. These findings provide insights into the physiopathological mechanisms of chronic hepatitis B infection, systemic lupus erythematosus, and gestational diabetes mellitus underlying systemic immune responses during mid- and late-stage pregnancy.NEW & NOTEWORTHY There are significant differences in three subtypes of memory/effector T cells (HOPX+ CD4+ T cells, ZNF683+CD8+ T cells, and KLRB1+CD8+ T cells) between mid- and late pregnancy. In late pregnancy, intercellular interaction was enhanced and effector CD8+ T cells highly expressed infection-related pathways. A rare T cell subtype, "XIST+ T cells," may be involved in the regulation of immune-related gene transcription and translation with a strong female bias.
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Affiliation(s)
- Fan Gao
- Gene Joint Laboratory, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, People's Republic of China
| | - Xia Li
- Department of Gynecology and Obstetrics, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, People's Republic of China
| | - Hongyan Wang
- Department of Gynecology and Obstetrics, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, People's Republic of China
| | - Zhen Xu
- Gene Joint Laboratory, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, People's Republic of China
| | - Wenjun Qian
- Department of Gynecology and Obstetrics, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, People's Republic of China
| | - Guiqin Bai
- Gene Joint Laboratory, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, People's Republic of China
- Department of Gynecology and Obstetrics, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, People's Republic of China
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Ochwoto M, Matiang’i M, Machuki Onchieku N, Ndoria S, Matoke L, Otinga M, Zablon J, Mathebula E, Matoke-Muhia D. The feasibility and impact of deploying a four-tests panel at antenatal care in primary health care facilities of a developing country, Kenya. Front Public Health 2024; 12:1399612. [PMID: 39655256 PMCID: PMC11626212 DOI: 10.3389/fpubh.2024.1399612] [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: 03/12/2024] [Accepted: 10/15/2024] [Indexed: 12/12/2024] Open
Abstract
Introduction Contracting HIV, syphilis, hepatitis B virus (HBV), and malaria during pregnancy significantly affects the health of the woman, the pregnancy, and the unborn child. The World Health Organization (WHO) recommends testing pregnant women for these infections to achieve triple elimination of mother-to-child transmissions. However, this goal has not been fully realized in low- to medium-income countries, primarily due to segmented testing practices. This study aimed to investigate the effect of introducing a four-tests panel on the quality of antenatal care (ANC) among pregnant women attending selected Primary Health Care facilities in Kenya. Methods Using a multi-design approach, we analyzed ANC medical records from 577 pregnant women attending eight facilities across four different counties. Blood from the women fingerpick was tested for HIV, Syphilis Hepatitis B Virus and Malaria using the four-tests panel and the results compared to those in the medical records. Results Out of 577 ANC women, only 8.3% had test results for all four infections available. The majority of the mothers had been tested for syphilis (93.7%), HIV (78.5%), and malaria (62.6%), only 19.5% had been tested for HBV. Testing the women using the 4-tests panel yielded positivity rates of 6.9% for HIV, 0.9% for syphilis, 1.9% for malaria, and 1.1% for HBV. Among those without previous test results, the positivity rate was 2.8% for syphilis, 13.8% for HIV (with 10.6% testing positive for recent p24 infections, F = 24.876, p < 0.001), 2.3% for malaria, and 4.5% for HBV, with 83.3% of these individuals having no prior test results. The mean positivity rate of those tested using the 4-tests panel compared to segmented single tests was significantly different. The panel was cost-effective and user-friendly for healthcare workers, and in facilities facing staff shortages, it reduced turnaround time and workloads by half. The use of the panel also improved the profiling of ANC mothers and enhanced data management for the four infections by 91.7%. Conclusion Adopting the 4-tests panel has the potential to improve test result outputs, enhance the quality-of-service delivery, and contribute significantly to the achievement of triple elimination goals.
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Affiliation(s)
- Missiani Ochwoto
- Innovation Technology Transfer Division, Kenya Medical Research Institute (KEMRI), Nairobi, Kenya
| | - Micah Matiang’i
- School of Medical Sciences, AMREF International University (AMIU), Nairobi, Kenya
| | - Noah Machuki Onchieku
- Centre for Biotechnology Research Development (CBRD), Kenya Medical Research Institute (KEMRI), Nairobi, Kenya
| | - Simon Ndoria
- School of Medical Sciences, AMREF International University (AMIU), Nairobi, Kenya
| | - Lydia Matoke
- Centre for Biotechnology Research Development (CBRD), Kenya Medical Research Institute (KEMRI), Nairobi, Kenya
| | - Maureen Otinga
- Centre for Biotechnology Research Development (CBRD), Kenya Medical Research Institute (KEMRI), Nairobi, Kenya
| | - Jeremiah Zablon
- Laboratory Medicine and Pathology Department, Brown University, Providence, RI, United States
| | - Evans Mathebula
- Abbott Rapid Diagnostics, Abbott, Woodmead, South Africa
- School of Health Systems and Public Health, Faculty of Health Science, University of Pretoria, Pretoria, South Africa
| | - Damaris Matoke-Muhia
- Centre for Biotechnology Research Development (CBRD), Kenya Medical Research Institute (KEMRI), Nairobi, Kenya
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Angelice GP, Roque PH, Valente G, Galvão K, Villar LM, Mello VM, Mello FCA, Lago BV. Evaluation of Interfering RNA Efficacy in Treating Hepatitis B: Is It Promising? Viruses 2024; 16:1710. [PMID: 39599825 PMCID: PMC11598949 DOI: 10.3390/v16111710] [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: 08/05/2024] [Revised: 09/27/2024] [Accepted: 09/27/2024] [Indexed: 11/29/2024] Open
Abstract
BACKGROUND Despite an existing safe and effective vaccine for hepatitis B virus (HBV), it is still a major public health concern. Nowadays, several drugs are used to treat chronic hepatitis B; however, full healing remains controversial. The viral covalently closed circular DNA (cccDNA) formed by HBV forms a major challenge in its treatment, as does the ability of HBV to integrate itself into the host genome, which enables infection reactivation. Interfering RNA (RNAi) is a gene-silencing post-transcriptional mechanism which forms as a promising alternative to treat chronic hepatitis B. The aim of the present review is to assess the evolution of hepatitis B treatment approaches based on using RNA interference. METHODS Data published between 2016 and 2023 in scientific databases (PubMed, PMC, LILACS, and Bireme) were assessed. RESULTS In total, 76,949 articles were initially identified and quality-checked, and 226 eligible reports were analyzed in depth. The main genomic targets, delivery systems, and major HBV therapy innovations are discussed in this review. This review reinforces the therapeutic potential of RNAi and identifies the need for conducting further studies to fill the remaining gaps between bench and clinical practice.
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Yuan X, Shao Y, Huang R, Seery S, Wang H, Hu N, Wen L, Lin X, Zhang L. Understanding the influence of cytokines in intrauterine hepatitis B transmission: A cross-sectional study in China. Cytokine 2024; 181:156670. [PMID: 38901264 DOI: 10.1016/j.cyto.2024.156670] [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: 12/06/2023] [Revised: 04/15/2024] [Accepted: 06/05/2024] [Indexed: 06/22/2024]
Abstract
Cytokines may related to intrauterine Hepatitis B virus (HBV) transmission. 205 HBsAg(+) pregnant cases and 74 HBsAg(-) women were included. Neonatal blood samples were taken within 24 h of delivery and before HBV vaccinations. Serological HBV biomarkers and cytokines were detected. 21.9 % of the newborns from HBsAg(+) women were intrauterinally transmitted, including 7.3 % with dominant transmission (DBT) and 14.6 % occult transmission (OBT). HBV DNA load (odd ratio [OR], 1.44; 95 % confidence interval [CI], 1.05-1.98), interferon-γ (IFN-γ) (OR, 1.01; 95 %CI, 1.00-1.02) and toll-like receptor 9 (TLR9) (OR, 1.27; 95 %CI, 1.06-1.52) positively correlated with DBT. Only IFN-γ (OR, 1.01; 95 %CI, 1.00-1.01) positively associated with OBT. According to the generated restricted cubic spline, TLR9 was positively correlates with rise of DBT in a log-shape. It may be possible to develop a nomogram which intercalates these factors to predict intrauterine HBV transmissions. Further research should consider immune processes involved in chorioamnionitis.
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Affiliation(s)
- Xiaojie Yuan
- Department of Epidemiology, School of Public Health, Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, Air Force Medical University, Xi'an, China
| | - Yuzhang Shao
- Beijing Enze Kangtai Biological Technology Co., Ltd., Beijing, China
| | - Rui Huang
- Weinan Vocational &Technical College, Xi'an, China
| | - Samuel Seery
- Faculty of Health and Medicine, Division of Health Research, Lancaster University, Lancaster, United Kingdom
| | | | - Ni Hu
- Xi'an Center for Disease Control and Prevention, Xi'an, China
| | - Leji Wen
- State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Innovation Platform for Industry-Education Integration in Vaccine Research, School of Public Health, Xiamen University, Xiamen, China
| | - Xin Lin
- State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Innovation Platform for Industry-Education Integration in Vaccine Research, School of Public Health, Xiamen University, Xiamen, China
| | - Lei Zhang
- State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Innovation Platform for Industry-Education Integration in Vaccine Research, School of Public Health, Xiamen University, Xiamen, China.
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Gao F, Li X, Wang X, Liu H, Zhang W, Zhang Y, Jia Y, Zhao Z, Bai G. Differences between Chronically Hepatitis B Virus-Infected Pregnant Women with and without Intrafamilial Infection: From Viral Gene Sequences to Clinical Manifestations. Intervirology 2024; 67:72-82. [PMID: 38934174 DOI: 10.1159/000539994] [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: 12/14/2023] [Accepted: 06/19/2024] [Indexed: 06/28/2024] Open
Abstract
INTRODUCTION This study aimed to investigate the differences between pregnant women with chronic hepatitis B virus (HBV) infection and intrafamilial infection and those without intrafamilial infection. METHODS HBV-DNA was extracted from the sera of 16 pregnant women with chronic hepatitis B (CHB) and their family members for gene sequencing and phylogenetic analyses. A total of 74 pregnant women with CHB were followed up from the second trimester to 3 months postpartum. Viral markers and other laboratory indicators were compared between pregnant women with CHB with and without intrafamilial infection. RESULTS The phylogenetic tree showed that HBV lines in the mother-spread pedigree shared a node, whereas there was an unrelated genetic background for HBV lines in individuals without intrafamilial infection. From delivery to 3 months postpartum, compared with those without intrafamilial infection, pregnant women with intrafamilial infection were related negatively to HBV-DNA (β = -0.43, 95% confidence interval [CI]: -0.76 to -0.12, p = 0.009), HBeAg (β = -195.15, 95% CI: -366.35 to -23.96, p = 0.027), and hemoglobin changes (β = -8.09, 95% CI: -15.54 to -0.64, p = 0.035) and positively to changes in the levels of alanine aminotransferase (β = 73.9, 95% CI: 38.92-108.95, p < 0.001) and albumin (β = 2.73, 95% CI: 0.23-5.23, p = 0.033). CONCLUSION The mother-spread pedigree spread model differs from that of non-intrafamilial infections. Pregnant women with intrafamilial HBV infection have less hepatitis flares and liver damage, but their HBV-DNA and HBeAg levels rebound faster after delivery, than those without intrafamilial infection by the virus.
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Affiliation(s)
- Fan Gao
- Clinical Research Center, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Xia Li
- Department of Gynecology and Obstetrics, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Xiaona Wang
- Department of Gynecology and Obstetrics, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Hankui Liu
- BGI Genomics, BGI-Shenzhen, Shenzhen, China
| | - Wentao Zhang
- Department of Gynaecology and Obstetrrics, Xi'an No. 3 Hospital, Xi'an, China
| | - Yidan Zhang
- Department of Gynaecology and Obstetrrics, Xi'an Fourth Hospital, Xi'an, China
| | - Yanju Jia
- Department of Gynecology and Obstetrics, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Ziyan Zhao
- Department of Gynecology and Obstetrics, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Guiqin Bai
- Department of Gynecology and Obstetrics, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
- Gene Joint Laboratory, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
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Martínez-Gallego J, Castro-Arroyave D, Quintero JC, de la Hoz F, Montoya M, Palacio I, Navas MC, Rojas C. Factors associated with hepatitis B virus infection in indigenous communities of Colombia. BIOMEDICA : REVISTA DEL INSTITUTO NACIONAL DE SALUD 2024; 44:144-154. [PMID: 39088527 PMCID: PMC11315589 DOI: 10.7705/biomedica.7243] [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: 10/12/2023] [Accepted: 02/20/2024] [Indexed: 08/03/2024]
Abstract
Introduction. Colombia is home to 2 million indigenous people who live in conditions of poverty and with health deficiencies, making them vulnerable to contracting hepatitis B (HBV). Amazonas has a high virus prevalence, and there are barriers to accessing vaccination; thus, part of the population is susceptible to infection. Objective. To identify factors associated with HBV in Colombian indigenous people. Materials and Methods. A case-control study of people over 18 years from four departments of Colombia. Cases were identified through the national hepatitis B notification registry (2015-2022). Controls were selected and matched to cases (2:1) by age, sex, ethnicity, and department. Sociodemographic characteristics, factors associated with contact with body fluids, cultural practices, and vaccination history were identified by means of a survey. The ethics committee of the Universidad de Antioquia approved the project. Results. Seventy five cases and 150 controls from 13 ethnic groups were surveyed. Amazonas contributed 49% of participants, 83% were women, and the median age of cases was 30 years (IQ range: 27-37). The associated factors were a family history of hepatitis B [adjusted OR: 2.61 (95% CI: 1.09-6.27)] and, in women, the number of pregnancies [adjusted OR: 1.61 (95% CI 1.02- 2.54)]. The vaccination history showed a protective effect, but the association was not significant. Conclusion. Aspects associated with family life and unprotected sexual relations seem to be responsible for the potential transmission of the virus. It was not possible to identify associated cultural practices. Innovative and differential strategies are required for indigenous people to achieve a reduction of HBV.
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Affiliation(s)
- Jaime Martínez-Gallego
- Grupo de Epidemiología, Facultad Nacional de Salud Pública, Universidad de Antioquia, Medellín, ColombiaUniversidad de AntioquiaUniversidad de AntioquiaMedellínMedellín
| | - Diana Castro-Arroyave
- Grupo de Estudio en Pedagogía, Infancia y Desarrollo Humano - GEPIDH, Facultad de Educación, Universidad de Antioquia, Medellín, ColombiaUniversidad de AntioquiaUniversidad de AntioquiaMedellínMedellín
| | - Juan Carlos Quintero
- Grupo de Epidemiología, Facultad Nacional de Salud Pública, Universidad de Antioquia, Medellín, ColombiaUniversidad de AntioquiaUniversidad de AntioquiaMedellínMedellín
| | - Fernando de la Hoz
- Facultad de Medicina, Universidad Nacional de Colombia, Bogotá, D. C., ColombiaUniversidad Nacional de ColombiaUniversidad Nacional de ColombiaBogotáD. CBogotá
| | - Melissa Montoya
- Grupo de Gastrohepatología, Facultad de Medicina, Universidad de Antioquia, Medellín, ColombiaUniversidad de AntioquiaUniversidad de AntioquiaMedellínMedellín
| | - Isabela Palacio
- Grupo de Gastrohepatología, Facultad de Medicina, Universidad de Antioquia, Medellín, ColombiaUniversidad de AntioquiaUniversidad de AntioquiaMedellínMedellín
| | - María Cristina Navas
- Grupo de Gastrohepatología, Facultad de Medicina, Universidad de Antioquia, Medellín, ColombiaUniversidad de AntioquiaUniversidad de AntioquiaMedellínMedellín
| | - Carlos Rojas
- Grupo de Epidemiología, Facultad Nacional de Salud Pública, Universidad de Antioquia, Medellín, ColombiaUniversidad de AntioquiaUniversidad de AntioquiaMedellínMedellín
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10
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Patel A, Dossaji Z, Gupta K, Roma K, Chandler TM, Minacapelli CD, Catalano K, Gish R, Rustgi V. The Epidemiology, Transmission, Genotypes, Replication, Serologic and Nucleic Acid Testing, Immunotolerance, and Reactivation of Hepatitis B Virus. GASTRO HEP ADVANCES 2023; 3:139-150. [PMID: 39129942 PMCID: PMC11307719 DOI: 10.1016/j.gastha.2023.10.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 03/31/2023] [Accepted: 10/18/2023] [Indexed: 08/13/2024]
Abstract
The epidemiology of Hepatitis B virus (HBV) has drastically changed in recent decades due to public health initiatives, including universal infant vaccination programs,urbanization driving global travel, and migration patterns. Despite screening of pregnant women and newborns significantly reducing the rate of perinatal transmission in certain parts of the world, other, perhaps more uncommon, routes (e.g., parenteral) have led to outbreaks in specific areas affected by the opioid epidemic and injection drug use. Although our current understanding of the effect of genetic variants of HBV is lacking, we review current knowledge and patterns of genetic variants with geographical predominance, pathophysiology, and clinical manifestations. Serologic and molecular markers are used to screen, identify phase and activity of infection, and monitor response to antivirals and/or reactivation. This review will provide the most up-to-date summary of the epidemiology, transmission, genotype, replication, and current methods of screening to follow the various phases of HBV, including immunotolerance and reactivation.
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Affiliation(s)
- Ankoor Patel
- Internal Medicine, Robert Wood Johnson Medical School, Rutgers Biomedical and Health Sciences (RBHS), Rutgers University, New Brunswick, New Jersey
- Division of Gastroenterology and Hepatology, Rutgers Robert Wood Johnson Medical School, New Brunswick, New Jersey
| | - Zahra Dossaji
- Internal Medicine, Kirk Kerkorian School of Medicine at the University of Nevada, Las Vegas, Nevada
| | - Kapil Gupta
- Division of Gastroenterology and Hepatology, Rutgers Robert Wood Johnson Medical School, New Brunswick, New Jersey
| | - Katerina Roma
- Internal Medicine, Kirk Kerkorian School of Medicine at the University of Nevada, Las Vegas, Nevada
| | - Toni-Marie Chandler
- Division of Gastroenterology and Hepatology, Rutgers Robert Wood Johnson Medical School, New Brunswick, New Jersey
| | - Carlos D. Minacapelli
- Division of Gastroenterology and Hepatology, Rutgers Robert Wood Johnson Medical School, New Brunswick, New Jersey
- Center for Liver Diseases and Masses, Rutgers Robert Wood Johnson Medical School, New Brunswick, New Jersey
| | - Kaitlyn Catalano
- Center for Liver Diseases and Masses, Rutgers Robert Wood Johnson Medical School, New Brunswick, New Jersey
| | - Robert Gish
- Hepatitis B Foundation, Doylestown, Pennsylvania
| | - Vinod Rustgi
- Division of Gastroenterology and Hepatology, Rutgers Robert Wood Johnson Medical School, New Brunswick, New Jersey
- Center for Liver Diseases and Masses, Rutgers Robert Wood Johnson Medical School, New Brunswick, New Jersey
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11
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Huang M, Gao Y, Liao D, Ma Y, Li J, Tang B, Hao Y, Zhang X, Yin S, Jiang X, Li J, Yin X, Li Y, Hu J, Liu Z. Effect of prophylactic antiviral intervention on T cell immunity in hepatitis B virus-infected pregnant women. BMC Pregnancy Childbirth 2023; 23:392. [PMID: 37245038 DOI: 10.1186/s12884-023-05700-8] [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: 02/03/2023] [Accepted: 05/11/2023] [Indexed: 05/29/2023] Open
Abstract
BACKGROUND Antiviral intervention in hepatitis B virus (HBV)-infected pregnant women can effectively reduce mother-to-child transmission. However, the immunological characteristics of pregnant women with chronic HBV infection and the effects of antiviral intervention during pregnancy on maternal immune response remain unknown. We aimed to investigate these effects by comparing mothers who received antiviral intervention during pregnancy with those who did not. METHODS Pregnant women positive for hepatitis B surface antigen and hepatitis B e-antigen (HBsAg+ HBeAg+) were enrolled at delivery, including 34 received prophylactic antiviral intervention during pregnancy (AVI mothers) and 15 did not (NAVI mothers). T lymphocyte phenotypes and functions were analysed using flow cytometry. RESULTS At delivery, maternal regulatory T cell (Treg) frequency in AVI mothers was significantly higher than that in NAVI mothers (P < 0.002), and CD4+ T cells in AVI mothers displayed a decreased ability to secrete IFN-γ (P = 0.005) and IL-21 (P = 0.043), but an increased ability to secrete IL-10 and IL-4 (P = 0.040 and P = 0.036), which represented a higher Treg frequency, enhanced Th2 response and suppressed Th1 response. Treg frequency among AVI mothers was correlated negatively with serum HBsAg and HBeAg levels. After delivery, the ability of CD4+ T cells or CD8+ T cells to secrete IFN-γ or IL-10 was similar and no significant difference in Treg frequency was found between the two groups. CONCLUSIONS Prophylactic antiviral intervention during pregnancy has an effect on T cell immunity in pregnant women, which was characterised by increased maternal Treg frequency, enhanced Th2 response and suppressed Th1 response at delivery.
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Affiliation(s)
- Meiting Huang
- Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China
| | - Yunfei Gao
- Department of Obstetrics and Gynaecology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China
- Department of Obstetrics and Gynaecology, Zengcheng Branch of Nanfang Hospital, Southern Medical University, Guangzhou, 511340, China
| | - Dandan Liao
- Department of Obstetrics and Gynaecology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China
| | - Yanchen Ma
- Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China
| | - Jinna Li
- Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China
| | - Bo Tang
- Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China
| | - Yaohua Hao
- Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China
| | - Xuelian Zhang
- Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China
| | - Shimin Yin
- Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China
| | - Xiaohuan Jiang
- Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China
| | - Jialin Li
- Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China
| | - Xueru Yin
- Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China
| | - Yongyin Li
- Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China
| | - Jing Hu
- Department of Nosocomial Infection Administration, Zhujiang Hospital, Southern Medical University, Guangzhou, 510280, China.
| | - Zhihua Liu
- Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
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12
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Ouoba S, Ko K, Lingani M, Nagashima S, Guingané AN, Bunthen E, Hussain MRA, Sugiyama A, Akita T, Ohisa M, Sanou MA, Traore O, Nassa JW, Sanou M, Takahashi K, Tinto H, Tanaka J. Intermediate hepatitis B virus infection prevalence among 1622 pregnant women in rural Burkina Faso and implications for mother-to-child transmission. Sci Rep 2023; 13:6115. [PMID: 37059812 PMCID: PMC10103033 DOI: 10.1038/s41598-023-32766-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2022] [Accepted: 04/01/2023] [Indexed: 04/16/2023] Open
Abstract
In highly endemic countries for hepatitis B virus (HBV) infection, childhood infection, including mother-to-child transmission (MTCT), represents the primary transmission route. High maternal DNA level (viral load ≥ 200,000 IU/mL) is a significant factor for MTCT. We investigated the prevalence of HBsAg, HBeAg, and high HBV DNA among pregnant women in three hospitals in Burkina Faso and assessed the performance of HBeAg to predict high viral load. Consenting pregnant women were interviewed on their sociodemographic characteristics and tested for HBsAg by a rapid diagnostic test, and dried blood spot (DBS) samples were collected for laboratory analyses. Of the 1622 participants, HBsAg prevalence was 6.5% (95% CI, 5.4-7.8%). Among 102 HBsAg-positive pregnant women in DBS samples, HBeAg was positive in 22.6% (95% CI, 14.9-31.9%), and viral load was quantified in 94 cases, with 19.1% having HBV DNA ≥ 200,000 IU/mL. HBV genotypes were identified in 63 samples and predominant genotypes were E (58.7%) and A (36.5%). The sensitivity of HBeAg by using DBS samples to identify high viral load in the 94 cases was 55.6%, and the specificity was 86.8%. These findings highlight the need to implement routine HBV screening and effective MTCT risk assessment for all pregnant women in Burkina Faso to enable early interventions that can effectively reduce MTCT.
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Affiliation(s)
- Serge Ouoba
- Department of Epidemiology, Infectious Disease Control and Prevention, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3, Kasumi, Minami-Ku, Hiroshima, 734-8551, Japan
- Unité de Recherche Clinique de Nanoro (URCN), Institut de Recherche en Science de la Santé (IRSS), Nanoro, Burkina Faso
| | - Ko Ko
- Department of Epidemiology, Infectious Disease Control and Prevention, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3, Kasumi, Minami-Ku, Hiroshima, 734-8551, Japan
| | - Moussa Lingani
- Unité de Recherche Clinique de Nanoro (URCN), Institut de Recherche en Science de la Santé (IRSS), Nanoro, Burkina Faso
| | - Shintaro Nagashima
- Department of Epidemiology, Infectious Disease Control and Prevention, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3, Kasumi, Minami-Ku, Hiroshima, 734-8551, Japan
| | - Alice N Guingané
- Unite de Formation Et de Recherche en Sciences de la Sante, Universite Joseph Ki-Zerbo, Ouagadougou, Burkina Faso
| | - E Bunthen
- Department of Epidemiology, Infectious Disease Control and Prevention, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3, Kasumi, Minami-Ku, Hiroshima, 734-8551, Japan
- Payment Certification Agency (PCA), Ministry of Health, Phnom Penh, Cambodia
| | - Md Razeen Ashraf Hussain
- Department of Epidemiology, Infectious Disease Control and Prevention, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3, Kasumi, Minami-Ku, Hiroshima, 734-8551, Japan
| | - Aya Sugiyama
- Department of Epidemiology, Infectious Disease Control and Prevention, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3, Kasumi, Minami-Ku, Hiroshima, 734-8551, Japan
| | - Tomoyuki Akita
- Department of Epidemiology, Infectious Disease Control and Prevention, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3, Kasumi, Minami-Ku, Hiroshima, 734-8551, Japan
| | - Masayuki Ohisa
- Department of Epidemiology, Infectious Disease Control and Prevention, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3, Kasumi, Minami-Ku, Hiroshima, 734-8551, Japan
| | - Moussa Abdel Sanou
- Unité de Recherche Clinique de Nanoro (URCN), Institut de Recherche en Science de la Santé (IRSS), Nanoro, Burkina Faso
| | - Ousmane Traore
- Unité de Recherche Clinique de Nanoro (URCN), Institut de Recherche en Science de la Santé (IRSS), Nanoro, Burkina Faso
| | - Job Wilfried Nassa
- Unité de Recherche Clinique de Nanoro (URCN), Institut de Recherche en Science de la Santé (IRSS), Nanoro, Burkina Faso
| | - Maimouna Sanou
- Unité de Recherche Clinique de Nanoro (URCN), Institut de Recherche en Science de la Santé (IRSS), Nanoro, Burkina Faso
| | - Kazuaki Takahashi
- Department of Epidemiology, Infectious Disease Control and Prevention, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3, Kasumi, Minami-Ku, Hiroshima, 734-8551, Japan
| | - Halidou Tinto
- Unité de Recherche Clinique de Nanoro (URCN), Institut de Recherche en Science de la Santé (IRSS), Nanoro, Burkina Faso
| | - Junko Tanaka
- Department of Epidemiology, Infectious Disease Control and Prevention, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3, Kasumi, Minami-Ku, Hiroshima, 734-8551, Japan.
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13
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Kane SV, Reau N. Clinical advances: pregnancy in gastroenterologic and hepatic conditions. Gut 2023; 72:1007-1015. [PMID: 36759153 DOI: 10.1136/gutjnl-2022-328893] [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: 11/30/2022] [Accepted: 01/27/2023] [Indexed: 02/11/2023]
Abstract
The fields of gastroenterology and hepatology, along with endoscopic practice, have seen significant changes and innovations to practice in just the past few years. These practice changes are not limited to gastroenterology, but maternal fetal medicine and the care of the pregnant person have become increasingly more sophisticated as well. Gastroenterologists are frequently called on to provide consultative input and/or perform endoscopy during pregnancy. To be able to provide the best possible care to these patients, gastroenterologists need to be aware of (and familiar with) the various nuances and caveats related to the care of pregnant patients who either have underlying gastrointestinal (GI) conditions or present with GI and liver disorders. Here, we offer a clinical update with references more recent than 2018, along with a few words about SARS-CoV-2 infection and its relevance to pregnancy.
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Affiliation(s)
- Sunanda V Kane
- Medicine, Mayo Clinic Minnesota, Rochester, Minnesota, USA
| | - Nancy Reau
- Medicine, Rush University Medical Center, Chicago, Illinois, USA
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14
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Li M, Sun F, Bi X, Lin Y, Yang L, Jiang T, Deng W, Lu Y, Zhang L, Yi W, Xie Y. Effects of antiviral therapy and drug withdrawal on postpartum hepatitis in pregnant women with chronic HBV infection. Hepatol Int 2023; 17:42-51. [PMID: 36109430 DOI: 10.1007/s12072-022-10412-w] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/03/2022] [Accepted: 08/13/2022] [Indexed: 02/07/2023]
Abstract
OBJECTIVE To investigate the effect of antiviral therapy and drug withdrawal on the incidence of hepatitis B after delivery in pregnant women with chronic hepatitis B virus (CHB) infection who received tenofovir disoproxil fumarate (TDF) treatment. METHODS Eligible CHB pregnant women were enrolled, and received TDF at 32 weeks gestation. The drug was stopped immediately or at 6 weeks after delivery. The HBV biomarkers and clinical biochemical parameters were monitored during gestation and 24 weeks after delivery. RESULTS There were 264 women completed the observation, including 96 untreated subjects in control group. Among 168 treated subjects, 131 cases stopped drug immediately after delivery and 37 cases delayed the drug withdrawal at 6 weeks after delivery. The incidence of postpartum hepatitis in control, immediate drug withdrawal, and delayed drug withdrawal were 28.1% (27/96), 23.7% (31/131), and 24.3% (9/37), showing no significant difference (χ2 = 0.607, p = 0.738). No factor was found to be associated with the occurrence of postpartum hepatitis. It's noteworthy that 96.3% of postpartum hepatitis in control group and 92.3% of postpartum hepatitis in immediate drug withdrawal group occurred within 12 weeks after delivery. While in delayed drug withdrawal group, the rate of postpartum hepatitis occurred within 12 weeks after delivery was 77.7%. CONCLUSION Withdrawing antiviral drug immediately or at 6 weeks after delivery did not affect the incidence of postpartum hepatitis in CHB women, but delaying drug withdrawal might delay the onset of postpartum hepatitis. CLINICAL TRIAL REGISTRATION NUMBER NCT03214302.
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Affiliation(s)
- Minghui Li
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, China.,Department of Hepatology Division 2, Peking University Ditan Teaching Hospital, Beijing, 100015, China
| | - Fangfang Sun
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, China
| | - Xiaoyue Bi
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, China
| | - Yanjie Lin
- Department of Hepatology Division 2, Peking University Ditan Teaching Hospital, Beijing, 100015, China
| | - Liu Yang
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, China
| | - Tingting Jiang
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, China
| | - Wen Deng
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, China
| | - Yao Lu
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, China
| | - Lu Zhang
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, China
| | - Wei Yi
- Department of Gynecology and Obstetrics, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, China.
| | - Yao Xie
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, China. .,Department of Hepatology Division 2, Peking University Ditan Teaching Hospital, Beijing, 100015, China.
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15
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Efficacy and safety of long-term postpartum antiviral therapy in hepatitis B virus-infected mothers receiving prophylactic tenofovir disoproxil fumarate treatment. Eur J Gastroenterol Hepatol 2023; 35:212-218. [PMID: 36574312 DOI: 10.1097/meg.0000000000002476] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
OBJECTIVES This study aimed to evaluate the efficacy and safety of long-term postpartum tenofovir disoproxil fumarate (TDF) therapy in hepatitis B virus (HBV)-infected mothers with high viral load. METHODS In this retrospective cohort study, HBV-infected mothers with HBV DNA>2 × 10 5 IU/mL who initiated TDF prophylaxis treatment during pregnancy were divided into TDF continuation and discontinuation groups according to whether they stopped TDF treatment within 3 months after birth or not. Virological and biochemical markers were collected before TDF treatment, antepartum and postpartum. RESULTS In 131 women followed for a median of 18 months postpartum, alanine aminotransferase (ALT) abnormality rate was significantly lower in TDF continuation group vs. discontinuation group (39.4% vs. 56.9%, P = 0.045), and continuous TDF therapy in postpartum was independently associated with lower risk of ALT flares [OR = 0.308, 95% confidence interval (CI), 0.128-0.742; P = 0.009]. Long-term postpartum TDF treatment can promote the decline of hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) levels, but the HBeAg seroconversion rate in two groups was not significant (15.5% vs. 11.7%, P = 0.541). There were no statistical differences in bone metabolism markers between two groups ( P > 0.05). Compared with the TDF discontinuation group, TDF continuation group had a significantly lower estimated glomerular filtration rate level and higher creatinine level in postpartum but within normal ranges ( P < 0.05). CONCLUSIONS For pregnant women who received prophylactic TDF treatment, long-term TDF therapy continued in postpartum can reduce the risk of ALT flares and promote the rapid decline of HBeAg and HBsAg levels.
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16
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Abstract
Liver disease in pregnancy often requires diagnostic and therapeutic considerations that are unique to pregnancy. Liver disease in pregnancy is commonly thought of as either liver disease unique to pregnancy, chronic liver disease, or liver disease coincidental to pregnancy. This review summarizes the approach to evaluation of liver disease in pregnancy.
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Affiliation(s)
- Gres Karim
- Department of Medicine, Mount Sinai Beth Israel, 350 East 17th Street, 20th Floor, New York, NY 10003, USA
| | - Dewan Giri
- Department of Medicine, Mount Sinai Beth Israel, 350 East 17th Street, 20th Floor, New York, NY 10003, USA
| | - Tatyana Kushner
- Division of Liver Diseases, Icahn School of Medicine at Mount Sinai, One Gustave L Levy Place, Box 1123, New York, NY 10023, USA; Department of Obstetrics, Gynecology, and Reproductive Sciences, Icahn School of Medicine at Mount Sinai, One Gustave L Levy Place, Box 1123, New York, NY 10023, USA.
| | - Nancy Reau
- Division of Hepatology, Rush University Medical Center, 1725 West Harrison Street
- Suite 319, Chicago, IL 60612, USA
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17
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Zhang L, Jiang T, Yang Y, Deng W, Lu H, Wang S, Liu R, Chang M, Wu S, Gao Y, Hao H, Shen G, Xu M, Chen X, Hu L, Yang L, Bi X, Lin Y, Lu Y, Jiang Y, Li M, Xie Y. Postpartum hepatitis and host immunity in pregnant women with chronic HBV infection. Front Immunol 2023; 13:1112234. [PMID: 36685527 PMCID: PMC9846060 DOI: 10.3389/fimmu.2022.1112234] [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: 11/30/2022] [Accepted: 12/16/2022] [Indexed: 01/06/2023] Open
Abstract
In order to develop immune tolerant to the fetal, maternal immune system will have some modification comparing to the time before pregnancy. Immune tolerance starts and develops at the maternal placental interface. In innate immunity, decidual natural killer (dNK) cells, macrophages and dendritic cells play a key role in immue tolerance. In adaptive immunity, a moderate increase of number and immune inhibition function of regulatory T cells (Treg) are essential for immune tolerance. The trophoblast cells and immune cells expressing indoleamine 2,3-dioxygenase (IDO), the trophoblast cells expressing HLA-G, and Th1/Th2 shifting to Th2 dominant and Th17/Treg shifting to Treg domiant are in favor of maternal fetal immune tolerance. Steroids (estrogen and progesterone) and human chorionic gonadotropin (HCG) also participate in immune tolerance by inducing Treg cells or upregulating immunosuppressive cytokines. Most of the patients with chronic HBV infection are in the "HBV immune tolerance period" before pregnancy, and the liver disease is relatively stable during pregnancy. In chronic HBV infection women, after delivery, the relative immunosuppression in vivo is reversed, and Th1 is dominant in Th1/Th2 and Th17 is dominant in Th17/Treg balance. After delivery, the number of Treg decrease and NK cells increase in quantity and cytotoxicity in peripheral blood. Liver NK cells may cause liver inflammation through a non-antigen specific mechanism. After delivery, the number of CD8+ T cells will increase and HBV specific T cell response recovers from the disfunction in pregnancy. Under the background of postpartum inflammation, the rapid decrease of cortisol after delivery, and especially the enhancement of HBV specific T cell response induced by HBV DNA and cytokines, are the main reasons for postpartum hepatitis. HBeAg positive, especially HBeAg<700 S/CO, and HBV DNA>3-5Log10IU/ml are risk factors for postpartum hepatitis. Antiviral treatment in late pregnancy can reduce the incidence of mother to child transmission (MTCT) in chronic HBV infection women. Chronic HBV infection women have hepatitis both during pregnancy and more often in 12 weeks postpartum. It is generally agreed that postpartum hepatitis is mild symptoms and self-limited. Delaying drug withdrawal to 48 weeks can increase the seroconversion rate of HBeAg in delivery women with elevated alanine aminotransferase (ALT) in pregnancy.
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Affiliation(s)
- Lu Zhang
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Tingting Jiang
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Ying Yang
- Hepatology Department 2, Xingtai Second Hospital, Xingtai, China
| | - Wen Deng
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Huihui Lu
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China,Department of Obstetrics and Gynecology, Wuhan Children’s Hospital (Wuhan Maternal and Child Healthcare Hospital), Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Shiyu Wang
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Ruyu Liu
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Min Chang
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Shuling Wu
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Yuanjiao Gao
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Hongxiao Hao
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Ge Shen
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Mengjiao Xu
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Xiaoxue Chen
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Leiping Hu
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Liu Yang
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Xiaoyue Bi
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Yanjie Lin
- Department of Hepatology Division 2, Peking University Ditan Teaching Hospital, Beijing, China
| | - Yao Lu
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China,*Correspondence: Yao Lu, ; Yuyong Jiang, ; Minghui Li, ; Yao Xie,
| | - Yuyong Jiang
- Center of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing, China,*Correspondence: Yao Lu, ; Yuyong Jiang, ; Minghui Li, ; Yao Xie,
| | - Minghui Li
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China,Department of Hepatology Division 2, Peking University Ditan Teaching Hospital, Beijing, China,*Correspondence: Yao Lu, ; Yuyong Jiang, ; Minghui Li, ; Yao Xie,
| | - Yao Xie
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China,Department of Hepatology Division 2, Peking University Ditan Teaching Hospital, Beijing, China,*Correspondence: Yao Lu, ; Yuyong Jiang, ; Minghui Li, ; Yao Xie,
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Zhou M, Cai H, Yi W, Gao X. A Nonlinear Relationship Between ALT Levels at Delivery and the Risk of Postpartum ALT Flares in Pregnant Women with Chronic Hepatitis B. Int J Med Sci 2023; 20:247-253. [PMID: 36794153 PMCID: PMC9925984 DOI: 10.7150/ijms.79663] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/08/2022] [Accepted: 01/14/2023] [Indexed: 02/04/2023] Open
Abstract
Background: The aim of the present study was to investigate the association between alanine aminotransferase (ALT) levels at delivery and postpartum ALT flares among women with chronic hepatitis B (CHB). Methods: Pregnant women with CHB from November 2008 to November 2017 were included in this retrospective study. Multivariable logistic regression analysis and a generalized additive model were performed to determine both linear and nonlinear relationships between ALT levels at delivery and postpartum ALT flares. Stratification analysis was performed to test for effect modifications in subgroups. Results: A total of 2643 women were enrolled. Multivariable analysis indicated that ALT levels at delivery were positively associated with postpartum ALT flares (odds ratio (OR) 1.02, 95% confidence interval (CI) 1.01-1.02, P < 0.0001). When ALT levels were converted to a categorical variable, the ORs and 95% CIs in quartiles 3 and 4 versus quartile 1 were 2.26 (1.43-3.58) and 5.34 (3.48-8.22), respectively (P for trend < 0.001). When ALT levels were dichotomized into a categorical variable according to clinical cutoffs (40 U/L or 19 U/L), the ORs and 95% CIs were 3.06 (2.05-4.57) and 3.31 (2.53-4.35), respectively (P < 0.0001). The ALT level at delivery was also found to have a nonlinear relationship with postpartum ALT flares. The relationship followed an inverted U-shaped curve. Conclusions: The ALT level at delivery was positively correlated with postpartum ALT flares in women with CHB when the ALT level was less than 182.8 U/L. The ALT cutoff (19 U/L) at delivery was more sensitive to predict the risk of ALT flares postpartum.
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Affiliation(s)
- Mingfang Zhou
- Department of Obstetrics and Gynecology, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, China
| | - Haodong Cai
- Hepatology clinic, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, China
| | - Wei Yi
- Department of Obstetrics and Gynecology, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, China
| | - Xuesong Gao
- Department of General Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, China
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19
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Demissie M, Weldekidan HA, Yosef Y, Sori SA, Tsega D, Jiru HD, Derribow AB, Tetema MD, Jima GB, Zeleke FT, Endeshew F, Abeje S. Timing of Hepatitis B Vaccine Birth Dose in Exposed Newborns, Southwest Ethiopia: A Cross-Sectional Study. SAGE Open Nurs 2023; 9:23779608231187258. [PMID: 37457619 PMCID: PMC10345928 DOI: 10.1177/23779608231187258] [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: 03/17/2023] [Revised: 06/19/2023] [Accepted: 06/24/2023] [Indexed: 07/18/2023] Open
Abstract
Introduction Hepatitis B virus disease is a global acute and chronic communicable disease. Mother-to-child transmission is the reason for high carrier rates. Unvaccinated newborns infected through mother-to-child transmission are at >95% risk of developing chronic hepatitis B virus disease. Vaccination is the most effective measure to reduce the global incidence of hepatitis B virus disease. Despite the World Health Organization's target to achieve 90% of the hepatitis B vaccine birth dose by 2030, little is known about the vaccination status of exposed newborns. Objective The present study aimed to determine the timing of the hepatitis B vaccine birth dose in exposed newborns in Southwest Ethiopia. Methods An institution-based cross-sectional study was employed on 422 systematically selected exposed newborns from April 2, 2022, to August 28, 2022. A pretested, interviewer-administered questionnaire was used for data collection. Data were entered into Epi data 3.1 and exported into SPSS version 23 software for analysis. Both bivariable and multivariable binary logistic regressions were performed. Variables with a p-value <.05 at a 95% confidence interval (CI) were considered statistically significant. Results The proportion of neonates who received their first dose of the hepatitis B vaccine on time was 57 (42.5%) (95% CI: 38.3-46.1%). A higher likelihood of vaccinating their exposed newborns on time was associated with formal education (adjusted odds ratio [AOR] = 3.01, 95% CI: 2.21-7.09), four or more ANC visits (AOR = 2.33, 95% CI: 2.05-6.21), and husband engagement (AOR = 4.31, 95% CI: 2.03-6.34). Conclusion The proportion of timely initiation of the hepatitis B vaccine birth dose in Southwest Ethiopia was low. Thus, strengthening health education on the hepatitis B vaccine, encouraging women to have at least four ANC visits, and encouraging male involvement help improve the timely administration of the hepatitis B vaccine.
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Affiliation(s)
- Mebratu Demissie
- Department of Midwifery, College of Medicine and Health Science, Wolkite University, Wolkite, Ethiopia
| | - Haregwa Asnake Weldekidan
- Department of Midwifery, College of Medicine and Health Science, Wolkite University, Wolkite, Ethiopia
| | - Yirgalem Yosef
- Department of Midwifery, College of Medicine and Health Science, Wolkite University, Wolkite, Ethiopia
| | - Seboka Abebe Sori
- Department of Midwifery, College of Medicine and Health Science, Wolkite University, Wolkite, Ethiopia
| | - Daniel Tsega
- Department of Midwifery, College of Medicine and Health Science, Wolkite University, Wolkite, Ethiopia
| | - Hirut Dinku Jiru
- Department of Midwifery, College of Medicine and Health Science, Wolkite University, Wolkite, Ethiopia
| | - Aberash Beyene Derribow
- Department of Midwifery, College of Medicine and Health Science, Wolkite University, Wolkite, Ethiopia
| | - Mesfin Difer Tetema
- Department of Midwifery, College of Medicine and Health Science, Wolkite University, Wolkite, Ethiopia
| | - Gudeta Beriso Jima
- Department of Midwifery, College of Medicine and Health Science, Wolkite University, Wolkite, Ethiopia
| | - Fentahun Temene Zeleke
- Department of Midwifery, College of Medicine and Health Science, Wolkite University, Wolkite, Ethiopia
| | - Fikremariam Endeshew
- Department of Midwifery, College of Medicine and Health Science, Wolkite University, Wolkite, Ethiopia
| | - Seblework Abeje
- Department of Biochemistry, College of Medicine and Health Science, Wolkite University, Wolkite, Ethiopia
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20
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Thilakanathan C, Kayes T, Di Girolamo J, Nguyen V, Glass A, Manandhar S, Lawler J, Meredith C, Maley M, Lloyd A, Levy MT. Predicting hepatitis B e Antigen seroconversion after pregnancy-The SydPregScore. Liver Int 2023; 43:69-76. [PMID: 35861306 PMCID: PMC10087847 DOI: 10.1111/liv.15372] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/14/2022] [Revised: 06/30/2022] [Accepted: 07/19/2022] [Indexed: 01/04/2023]
Abstract
BACKGROUND AND AIMS Achieving Hepatitis B e antigen seroconversion (HBeAg SC) at an earlier age confers a better prognosis. We examined baseline and post-partum factors associated with HBeAg SC after pregnancy. We developed a tool, the SydPregScore, to estimate the likelihood of HBeAg SC in the years after pregnancy. METHODS A retrospective analysis of an HBeAg-positive pregnant cohort was conducted. Variables including baseline age, parity, alanine aminotransferase level, HBV viral load, quantitative HBsAg, use of antiviral therapy and post-partum flare were collected. Univariate and multivariate Cox regression analyses to determine predictors of HBeAg SC and develop a predictor score were performed. RESULTS We analysed HBeAg SC rates in 220 pregnancies to 149 HBeAg-positive women from 2006 to 2019. At baseline, their median age was 33 (IQR 29-37), ALT 23 U/L (IQR 17-33) and viral load 8 log10 IU/mL (IQR 6.3-8.2 log10 IU/mL). The majority (133/198, 67.2%) received short-course antiviral therapy to prevent mother-to-child transmission, and 109/192 (56.8%) had a post-partum flare. HBeAg SC occurred in 74/220 (33.6%) after pregnancy (median follow-up 814 days, IQR 405-1531). Multivariate analysis identified baseline viral load <8 log10 IU/mL (HR 2.426 [1.224-4.809], p = .011), baseline ALT ≥2 ULN (HR 2.726 [1.299-5.721], p = .008) and age <35 (HR 2.859 [1.255-6.513], p = .012) to be positive predictors of HBeAg SC. The 'SydPreg Score' estimated the probability of HBeAg SC at 2000 days as 10%, 30%, 70% and 80% for 0, 1, 2, and 3 predictors respectively. CONCLUSION The SydPreg Score allows the prediction of HBeAg SC in the years after pregnancy. Even in those without elevated ALT, age <35 and viral load <8 log10 IU/mL can identify women with a good chance of subsequent HBeAg SC. Those without a chance may benefit from viral suppression.
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Affiliation(s)
- Cynthuja Thilakanathan
- Department of Gastroenterology and Hepatology, Liverpool Hospital, Sydney, Australia.,South Western Sydney Clinical School, University of New South Wales Sydney, Liverpool, Sydney, Australia
| | - Tahrima Kayes
- Department of Gastroenterology and Hepatology, Liverpool Hospital, Sydney, Australia
| | - Julia Di Girolamo
- Department of Gastroenterology and Hepatology, Liverpool Hospital, Sydney, Australia
| | - Vi Nguyen
- South Western Sydney Clinical School, University of New South Wales Sydney, Liverpool, Sydney, Australia
| | - Anne Glass
- Department of Gastroenterology and Hepatology, Liverpool Hospital, Sydney, Australia
| | - Sicha Manandhar
- Department of Gastroenterology and Hepatology, Liverpool Hospital, Sydney, Australia
| | - Joseph Lawler
- Department of Gastroenterology and Hepatology, Bankstown Hospital, Sydney, Australia
| | - Chris Meredith
- Department of Gastroenterology and Hepatology, Bankstown Hospital, Sydney, Australia
| | - Michael Maley
- South Western Sydney Clinical School, University of New South Wales Sydney, Liverpool, Sydney, Australia.,Sydney South West Pathology Service, Liverpool Hospital, Sydney, Australia
| | - Andrew Lloyd
- The Kirby Institute, University of New South Wales Sydney, Sydney, Australia
| | - Miriam T Levy
- Department of Gastroenterology and Hepatology, Liverpool Hospital, Sydney, Australia.,South Western Sydney Clinical School, University of New South Wales Sydney, Liverpool, Sydney, Australia
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21
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Presence of entry receptors and viral markers suggest a low level of placental replication of hepatitis B virus in a proportion of pregnant women infected with chronic hepatitis B. Sci Rep 2022; 12:17795. [PMID: 36272995 PMCID: PMC9588053 DOI: 10.1038/s41598-022-22699-8] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2022] [Accepted: 10/18/2022] [Indexed: 01/19/2023] Open
Abstract
The transplacental route of vertical transmission of Hepatitis B Virus (HBV) has been known for over a decade. Here we present evidence which suggest HBV can replicate in placenta. Forty-one HBsAg positive and 10 control pregnant women were enrolled in the study after obtaining informed consent. HBV positives were further divided in the High Viral Load (HVL) Group and Low Viral Load (LVL) Group according to INASL guidelines 2018. The Presence of the HBV DNA and expression of NTCP in the placenta was analyzed by qPCR/RT-qPCR and/or immunohistochemistry (IHC). The presence of cccDNA was assessed using Digital Droplet PCR while the presence of pre-genomic (pg) RNA was assessed through qRT-PCR and sequencing. The presence of HBeAg and HBcAg in the placenta was assessed by IHC. Immunostaining of NTCP, HBeAg and HBcAg on trophoblasts along with the presence of total HBV DNA, cccDNA and pgRNA indicated, that these cells are not only susceptible to HBV infection but may also support viral replication. This is further supported by the finding that trophoblasts of the several HBeAg seronegative samples harbored the HBeAg. Although, we did not find any correlation in NTCP expression and viral markers with viral load indicates placental replication may not aping hepatocytes. The presence of the HBV receptor, NTCP along with the presence of cccDNA, pgRNA, and HBeAg in placenta of HBV infected females without circulating HBeAg suggest that placenta act as a replication host.
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22
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Samadi Kochaksaraei G, Shaheen AA, Seow CH, Barkema HW, Coffin CS. Tenofovir disoproxil fumarate therapy to prevent hepatitis B virus vertical transmission-A review of maternal and infant outcomes. Liver Int 2022; 42:1712-1730. [PMID: 35312156 DOI: 10.1111/liv.15249] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/04/2021] [Revised: 01/19/2022] [Accepted: 03/17/2022] [Indexed: 02/13/2023]
Abstract
Hepatitis B virus (HBV) is a global health problem. Vertical transmission of HBV from HBV surface antigen (HBsAg)-positive mothers to their infants is the most common cause of HBV infection worldwide. The use of passive-active immunoprophylaxis is >90% effective in reducing the risk of vertical transmission, but immunoprophylaxis failure can occur in infants born to mothers with high viraemia. Thus, it is recommended that pregnant women with HBV-DNA level >200 000 IU/ml receive nucleos(t)ide analogue (NA) treatment [i.e. tenofovir disoproxil fumarate (TDF), lamivudine or telbivudine] during third trimester to prevent infant immunoprophylaxis failure. TDF is recommended as the first-line therapy based on available data on efficacy, safety and resistance profile. However, maternal immunological reconstitution following parturition can increase immune-mediated flares to viral antigens that is potentially exacerbated following TDF withdrawal. In this article, we review available data on the efficacy and safety of TDF administration to prevent HBV mother-to-child transmission. We also discuss changes in maternal viral markers [i.e. HBV-DNA, HBV e antigen and HBsAg] and alanine aminotransferase during follow-up post-partum in mothers received NA to prevent HBV vertical transmission.
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Affiliation(s)
- Golasa Samadi Kochaksaraei
- Division of Gastroenterology and Hepatology, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
| | - Abdel A Shaheen
- Division of Gastroenterology and Hepatology, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.,Department of Community Health Sciences, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
| | - Cynthia H Seow
- Division of Gastroenterology and Hepatology, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.,Department of Community Health Sciences, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
| | - Herman W Barkema
- Department of Community Health Sciences, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.,Department of Production Animal Health, Faculty of Veterinary Medicine, University of Calgary, Calgary, Alberta, Canada
| | - Carla S Coffin
- Division of Gastroenterology and Hepatology, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
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23
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Kayes T, Crane H, Symonds A, Dumond J, Cottrell M, Di Girolamo J, Manandhar S, Lim TH, Gane E, Kashuba A, Levy MT. Plasma and breast milk pharmacokinetics of tenofovir alafenamide in mothers with chronic hepatitis B infection. Aliment Pharmacol Ther 2022; 56:510-518. [PMID: 35599363 DOI: 10.1111/apt.17040] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/02/2022] [Revised: 05/06/2022] [Accepted: 05/08/2022] [Indexed: 01/26/2023]
Abstract
BACKGROUND Antenatal antiviral therapy (AVT) is effective in preventing mother-to-child transmission (MTCT) in chronic hepatitis B (CHB); tenofovir disoproxil fumarate (TDF) is the preferred agent. Tenofovir alafenamide (TAF) is a prodrug of tenofovir (TFV) similar to TDF, with improved bone and renal safety. There are no data on TAF breast milk pharmacokinetics and exposure to breastfeeding infants in CHB. AIM To assess the pharmacokinetics of TAF/TFV in breastfeeding women with CHB on TAF monotherapy. METHODS Pregnant women with CHB requiring AVT commenced TAF 25 mg daily at third trimester or postpartum. Sample collection occurred while breastfeeding and taking TAF for minimum 4 weeks. Maternal blood, breast milk and infant urine samples were collected. Drug concentrations were measured by LCMS/MS analyses using validated methods. Non-compartmental analyses were performed to quantify the pharmacokinetic parameters. RESULTS Eight women provided samples. In breast milk and plasma, median TAF half-life was 0.81 and 0.94 h, respectively, and Cmax 1.69 and 120.5 ng/ml, respectively. Median maternal breast milk to plasma (M/P) ratio of TAF was 0.029; for and TFV it was 2.809. The relative infant dose of TAF was 0.005% of maternal dose, well below safety threshold of 5-10%. TFV was detectable in three out of seven infant urine samples with median steady-state concentration of 5 ng/ml being 300-2500 times less than reported adult steady-state urine concentrations in those taking TAF and TDF, respectively. CONCLUSIONS In this first pharmacokinetic study of TAF monotherapy in breastfeeding women with CHB, concentrations of TAF and TFV were low in breast milk with negligible infant exposure, supporting the use of TAF to prevent MTCT.
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Affiliation(s)
- Tahrima Kayes
- Department of Gastroenterology and Hepatology, Liverpool Hospital, Sydney, New South Wales, Australia.,Ingham Institute of Applied Medical Research, Liverpool, New South Wales, Australia
| | - Harry Crane
- Department of Gastroenterology and Hepatology, Liverpool Hospital, Sydney, New South Wales, Australia.,Ingham Institute of Applied Medical Research, Liverpool, New South Wales, Australia
| | - Allison Symonds
- University of North Carolina Eshelman School of Pharmacy, Chapel Hill, North Carolina, USA
| | - Julie Dumond
- University of North Carolina Eshelman School of Pharmacy, Chapel Hill, North Carolina, USA
| | - Mackenzie Cottrell
- University of North Carolina Eshelman School of Pharmacy, Chapel Hill, North Carolina, USA
| | - Julia Di Girolamo
- Department of Gastroenterology and Hepatology, Liverpool Hospital, Sydney, New South Wales, Australia.,Ingham Institute of Applied Medical Research, Liverpool, New South Wales, Australia
| | - Sicha Manandhar
- Department of Gastroenterology and Hepatology, Liverpool Hospital, Sydney, New South Wales, Australia.,Ingham Institute of Applied Medical Research, Liverpool, New South Wales, Australia
| | - Tien Huey Lim
- Department of Gastroenterology and Hepatology, Middlemore Hospital, Auckland, New Zealand
| | - Edward Gane
- Faculty of Medicine, University of Auckland, Auckland, New Zealand
| | - Angela Kashuba
- University of North Carolina Eshelman School of Pharmacy, Chapel Hill, North Carolina, USA
| | - Miriam T Levy
- Department of Gastroenterology and Hepatology, Liverpool Hospital, Sydney, New South Wales, Australia.,Ingham Institute of Applied Medical Research, Liverpool, New South Wales, Australia.,South Western Sydney Clinical School, University of New South Wales Sydney, Liverpool, New South Wales, Australia
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24
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Antiviral Therapy for Prevention of Perinatal Hepatitis B Virus Transmission Reduces the Incidence of Postpartum Hepatitis Flare. BIOMED RESEARCH INTERNATIONAL 2022; 2022:7046955. [PMID: 35860799 PMCID: PMC9293540 DOI: 10.1155/2022/7046955] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/03/2022] [Revised: 06/11/2022] [Accepted: 06/20/2022] [Indexed: 11/23/2022]
Abstract
Background: Currently, there are few studies on the effect of prophylactic anti-hepatitis B virus (HBV) therapy (AVT) for mother-to-child transmission during pregnancy on postpartum hepatitis flare (PHF) and the risk factors for postpartum hepatitis flare in women with chronic hepatitis B infection. Aim: To analyze the effect of AVT on the postpartum hepatitis flare and risk factors related to postpartum hepatitis flare. Methods: This study retrospectively enrolled hepatitis B surface antigen (HBsAg)-positive and hepatitis B e antigen (HBeAg)-positive women with HBV DNA ≥ 106 IU/mL. Six hundred fourteen pregnant women were included: 444 in the anti-HBV therapy group (T-G) and 170 in the control group (C-G). To analyze the risk factors, women with alanine aminotransferase (ALT) flare (ALT > 40 U/L) were assigned to the PHF group (PHF-G, n = 355), and all the others were assigned to a non-PHF group (NPHF-G, n = 259). Results: At 6 weeks postpartum, ALT and AST levels were higher, and ALB levels were lower in the C-G than those in T-G (P < 0.05). Also, ALT (at baseline, pregnancy 32nd and 36th, intrapartum), AST (at pregnancy 32nd and 36th week, and intrapartum), HBcAb (at baseline, intrapartum), and HBV DNA (at intrapartum) of PHF-G were significantly higher than those of NPHF-G (P < 0.05). Multivariate analysis showed that ALT (OR = 1.067, P < 0.001) and HBcAb (OR = 1.213, P ≤ 0.001) in pregnant women were risk factors for PHF. The prophylactic anti-HBV for the prevention of perinatal HBV transmission (OR = 0.357, P < 0.001) was the protective factor for PHF. Conclusion: Pregnant women with prophylactic anti-HBV during the third trimester of pregnancy had a lower incidence of postpartum hepatitis flare, especially a lower risk of serious hepatitis flare. ALT and HBcAb in pregnant women were risk factors for PHF. Women infected with HBV should be closely monitored ALT during pregnancy and postpartum.
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25
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Quan M, Liu C, Li W, Xing HC. Antiviral Therapy for a Postpartum Flare in Women with Chronic HBV Infection Shortens the ALT Recovery Time and Reduces Hepatitis Re-Flare Rates within 4 years. Can J Gastroenterol Hepatol 2022; 2022:4753267. [PMID: 35770180 PMCID: PMC9236834 DOI: 10.1155/2022/4753267] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/26/2022] [Revised: 05/11/2022] [Accepted: 06/02/2022] [Indexed: 02/07/2023] Open
Abstract
Background Few studies explored whether anti-hepatitis B virus (HBV) therapy should be initiated during postpartum hepatitis flare. Aim This study aimed to analyze the effect of anti-HBV therapy on postpartum hepatitis flare and evaluate the prognosis within 4 years postpartum. Methods This retrospective study enrolled hepatitis B surface antigen (HBsAg)-positive and hepatitis B e antigen (HBeAg)-positive pregnant women with HBV DNA ≥ 106 IU/mL. A total of 152 pregnant women were included: 103 in the prophylactic anti-HBV therapy group (PT-G) and 49 in the non-prophylactic anti-HBV therapy group (NPT-G). The women with a postpartum flare were assigned to the anti-HBV therapy group (AT-G) and non-anti-HBV therapy group (NAT-G) to analyze the effect of postpartum anti-HBV therapy on hepatitis flare. Virological and biochemical parameters were assessed. Results Taking postpartum 12 weeks as the cutoff point, the ALT recovered time for postpartum flare women is shorter in AT-G (n = 16, 42.1%) or PT-G (n = 23, 34.8%) than in NAT-G (n = 14, 23.0%; x 2 = 4.067, P=0.044) or NPT-G (n = 4, 11.1%; x 2 = 5.579, P=0.018). Taking postpartum 26 weeks as the cutoff point, the ALT recovered time is shorter in AT-G (n = 35, 57.3%) or PT-G (n = 44, 66.7%) than in NAT-G (n = 32, 84.2%; x 2 = 7.707, P=0.006) or NPT-G (n = 16, 44.4%; x 2 = 4.749, P=0.029). Postpartum flare recovery time was positively correlated with HBV DNA level at delivery [r = 0.223, P=0.025, 95%CI (0.022～0.41)]. The hepatitis re-flare rates within postpartum 4 years in AT-G (n = 3, 9.68%) is lower than that in NAT-G (n = 24, 45.4%; x 2 = 14.003, P ≤ 0.001). The HBeAg, HBsAg, HBV DNA, and ALT level at postpartum 4 years in AT-G were lower than that in NAT-G (P < 0.001). Conclusion Anti-HBV therapy for postpartum hepatitis flare of women with chronic HBV could shorten the ALT recovery time and reduce hepatitis re-flare rates within 4 years of postpartum.
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Affiliation(s)
- Min Quan
- Center of Liver Diseases Division 3, Beijing Ditan Hospital, Capital Medical University, Bejing 100015, China
- Peking University Ditan Teaching Hospital, Beijing 100015, China
| | - Cong Liu
- Department of Infectious Diseases, The Second Hospital of Shanxi Medical University, Taiyuan, Shanxi 030000, China
| | - Wei Li
- Center of Liver Diseases Division 3, Beijing Ditan Hospital, Capital Medical University, Bejing 100015, China
- Peking University Ditan Teaching Hospital, Beijing 100015, China
| | - Hui-Chun Xing
- Center of Liver Diseases Division 3, Beijing Ditan Hospital, Capital Medical University, Bejing 100015, China
- Peking University Ditan Teaching Hospital, Beijing 100015, China
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26
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Hawkins C, Kang M, Bhattacharya D, Cloherty G, Kuhns M, Matining R, Thio C, Samaneka W, Chinula L, Mulinda N, Badal-Faesen S, Sugandhavesa P, Lama J, Gaseitsiwe S, Holzmayer V, Anderson M, Murphy R, Peters M. Hepatitis B surface antigen and hepatitis B RNA changes in HIV/hepatitis B virus co-infected participants receiving hepatitis B virus-active antiretroviral therapy. AIDS 2022; 36:975-984. [PMID: 35165216 PMCID: PMC9167724 DOI: 10.1097/qad.0000000000003193] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
INTRODUCTION With advances in hepatitis B virus (HBV) therapies, there is a need to identify serum biomarkers that assess the HBV covalently closed circular DNA (cccDNA) reservoir and predict functional cure in HIV/HBV co-infection. METHODS In this retrospective study, combining samples from HIV/HBV co-infected participants enrolled in two ACTG interventional trials, proportions achieving HBsAg less than 0.05 log10 IU/ml and HBV RNA less than log10 1.65 U/ml or not detected (LLoQ/NEG) in response to DUAL [tenofovir TDF+emtricitabine (FTC)] vs. MONO [FTC or lamivudine (3TC)] HBV-active ART, were measured. Predictors of qHBsAg less than 0.05 log10 IU/ml were evaluated in logistic regression models. RESULTS There were 88 participants [58% women, median age 34; 47 on DUAL vs. 41 on MONO HBV-active ART]. Twenty-one percent achieved HBsAg less than 0.05 log10 IU/ml (30% DUAL vs. 10% MONO). Time to HBsAg less than 0.05 log10 IU/ml was lower (P = 0.02) and the odds of achieving HBsAg less than 0.05 log10 IU/ml were higher (P = 0.07) in DUAL participants. HBV RNA became less than LLoQ/NEG in 47% (DUAL 60% vs. MONO 33%). qHBsAg less than 3 log10 IU/ml was the strongest predictor of HBsAg less than 0.05 log10 IU/ml. CONCLUSION This study supports current recommendations of TDF-based DUAL-HBV active ART for initial use in HIV/HBV co-infection. HBV RNA could be a useful marker of treatment response in HIV/HBV co-infected patients on HBV-active ART.
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Affiliation(s)
- Claudia Hawkins
- Department of Medicine, Feinberg School of Medicine, Northwestern University CRS, Chicago, Illinois
| | - Minhee Kang
- Center for Biostatistics in AIDS Research, Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts
| | - Debika Bhattacharya
- David Geffen School of Medicine, Division of Infectious Diseases, University of California, Los Angeles (UCLA), California
| | - Gavin Cloherty
- Infectious Diseases Research, Abbott, Abbott Park, Illinois
| | - Mary Kuhns
- Infectious Diseases Research, Abbott, Abbott Park, Illinois
| | - Roy Matining
- Center for Biostatistics in AIDS Research, Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts
| | - Chloe Thio
- Department of Medicine, Johns Hopkins University, Baltimore, Maryland, USA
| | | | - Lameck Chinula
- UNC Project Malawi CRS, UNC Department of Obstetrics and Gynecology's Division of Global Women's Health, Chapel Hill, North Carolina, USA
| | | | - Sharlaa Badal-Faesen
- Clinical HIV Research Unit, Department of Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
| | | | - Javier Lama
- Asociacion Civil Impacta Salud y Educacion, Lima, Peru, and Botswana Harvard School of Public Health AIDS Initiative Partnership, Botswana
| | - Simani Gaseitsiwe
- Clinical HIV Research Unit, Department of Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
| | - Vera Holzmayer
- Infectious Diseases Research, Abbott, Abbott Park, Illinois
| | - Mark Anderson
- Infectious Diseases Research, Abbott, Abbott Park, Illinois
| | - Robert Murphy
- Department of Medicine, Feinberg School of Medicine, Northwestern University CRS, Chicago, Illinois
| | - Marion Peters
- Department of Medicine, Feinberg School of Medicine, Northwestern University CRS, Chicago, Illinois
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Zhang L, Yang S, Yu Y, Wang S, Yu Y, Jin Y, Zhao A, Mao Y, Lu L. Prophylactic effect of tenofovir on viral reactivation in immunocompromised pregnant women living with hepatitis B virus. Hepatol Commun 2022; 6:2431-2440. [PMID: 35593183 PMCID: PMC9426410 DOI: 10.1002/hep4.1994] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/20/2022] [Revised: 04/05/2022] [Accepted: 04/25/2022] [Indexed: 02/05/2023] Open
Abstract
The appropriate prophylaxis for hepatitis B virus reactivation (HBVr) during gestation for immunocompromised pregnant women has yet to be determined. The prophylactic efficacy and safety of tenofovir disoproxil fumarate (TDF) in hepatitis B surface antigen (HBsAg)–positive patients and the HBVr risk in hepatitis B core antibody (HBcAb)–positive patients during gestation were investigated. Eligible pregnant women were diagnosed with rheumatic diseases and were administered prednisone (≤10 mg daily) with permitted immunosuppressants at screening. HBsAg‐positive participants were instructed to take TDF; those unwilling to take TDF were followed up as the control group. Propensity score matching was applied to control for differences in confounding factors between the HBcAb‐positive and uninfected groups. Hepatopathy, maternal, pregnancy, and safety outcomes were documented as endpoints. A cohort of 1292 women was recruited from 2017 to 2020, including 58 HBsAg‐positive patients (29 in each group). A total of 120 pairs in the HBcAb‐positive and noninfection groups were analyzed. Among HBsAg‐positive patients, 6 (20.7%) cases of hepatitis flare (hazard ratio [HR]: 7.44; 95% confidence interval [CI]: 1.50–36.89; p = 0.014) and 12 (41.4%) cases of HBVr (HR: 8.71; 95% CI: 2.80–27.17; p < 0.001) occurred in the control group, while 0 occurred in the TDF prophylaxis group. The HBV level at delivery was the lowest (1.6 log10 IU/ml) for those who received TDF during the pregestation period with a good safety profile. More adverse maternal outcomes were observed in the control group (odds ratio: 0.19, 95% CI: 0.05–0.77, p = 0.021), including one death from fulminant hepatitis and two cases of vertical transmission. No HBVr was recorded in HBcAb‐positive participants. Among immunocompromised pregnant women, prophylactic TDF during pregestation was necessary for HBsAg‐positive women, whereas regular monitoring was recommended for HBcAb‐positive women.
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Affiliation(s)
- Le Zhang
- Department of Rheumatology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.,Department of Pharmacy, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Shaoying Yang
- Department of Rheumatology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yongfu Yu
- Department of Biostatistics, School of Public Health, Key Laboratory of Public Health Safety of Ministry of Education, Fudan University, Shanghai, China
| | - Suli Wang
- Department of Rheumatology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yuetian Yu
- Department of Critical Care Medicine, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yi Jin
- Department of Obstetrics and Gynecology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Aimin Zhao
- Department of Obstetrics and Gynecology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yimin Mao
- Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.,Shanghai Institute of Digestive Disease, Shanghai, China
| | - Liangjing Lu
- Department of Rheumatology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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28
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Brown R, Goulder P, Matthews PC. Sexual Dimorphism in Chronic Hepatitis B Virus (HBV) Infection: Evidence to Inform Elimination Efforts. Wellcome Open Res 2022; 7:32. [PMID: 36212217 PMCID: PMC9520633 DOI: 10.12688/wellcomeopenres.17601.3] [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] [Accepted: 04/29/2022] [Indexed: 11/20/2022] Open
Abstract
Sexual dimorphism in infectious diseases refers to the different infection susceptibilities and outcomes between males and females, and has been described for many pathogens, including hepatitis B virus (HBV). HBV is a substantial global health problem, with close to 300 million people chronically infected, and accounting for a million deaths each year, with an urgent need for enhanced interventions to support progress towards elimination goals. Sexual dimorphism has a strong influence in HBV infection, with males more likely to be exposed, to develop chronic infection, and to suffer from complications including cirrhosis and hepatocellular carcinoma (HCC) compared to females. Different outcomes are driven by differential immune responses, sexual dimorphism of the liver, and androgen response elements in the HBV genome. The impact of sex may also vary with age, with changes at puberty and influences of menarche, pregnancy and menopause in females. In addition, gender has complex influences on education, beliefs, behaviour and access to / engagement with healthcare services, which may contribute to differences in diagnosis and treatment. Interplay between these complex factors, alongside other attributes of host, virus and the environment, accounts for different outcomes of infection. However, gaps remain in our understanding of sexual dimorphism in HBV, and little effort has previously been made to harness this knowledge for translational gains. In this review, we assimilate human and animal data to consider the mechanism, outcomes and impact of sexual dimorphism, and consider how these insights can be used to inform advances in surveillance, treatment and prevention for HBV infection.
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Affiliation(s)
- Robin Brown
- Harris Manchester College, University of Oxford, Oxford, Oxon, OX1 3TD, UK
| | - Philip Goulder
- Department of Paediatrics, University of Oxford, Oxford, Oxon, OX1 3SY, UK
| | - Philippa C. Matthews
- Harris Manchester College, University of Oxford, Oxford, Oxon, OX1 3TD, UK
- The Francis Crick Institute, London, London, NW1 1AT, UK
- Division of Infection and Immunity, University College London, London, WC1E 6BT, UK
- Department of Infectious Diseases, University College London Hospital, London, NW1 2BU, UK
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29
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Prevalence, genotype distribution and mutations of hepatitis B virus and the associated risk factors among pregnant women residing in the northern shores of Persian Gulf, Iran. PLoS One 2022; 17:e0265063. [PMID: 35271684 PMCID: PMC8912131 DOI: 10.1371/journal.pone.0265063] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2021] [Accepted: 02/22/2022] [Indexed: 12/18/2022] Open
Abstract
Background Considering perinatal transmission and the high rate of chronic hepatitis B virus (HBV) infection in infants, diagnosis of HBV infection during pregnancy and timely interventions are of great importance. Therefore, this study was performed to investigate the prevalence and genotype distribution of HBV infection and the associated risk factors among pregnant women in the northern shores of the Persian Gulf, South of Iran. Methods Serum samples of 1425 pregnant women were tested for the presence of HBsAg and HBcAb by ELISA (HBsAg one—Version ULTRA and HBc Ab ELISA kits, DIA.PRO, Milan, Italy). The seropositive samples were tested for the presence of HBV DNA by nested PCR, targeting S, X, pre-core (pre-C), and basal core promoter (BCP) regions of the HBV genome. The amplified fragments were sequenced by Sanger dideoxy sequencing technology to evaluate the genotype distribution and mutations of HBV infection by using the MEGA 7 software. The HBV seropositive pregnant women were tested for HCV and HIV coinfections by ELISA (HCV Ab and HIV Ab/Ag ELISA kits, DIA.PRO, Milan, Italy). Results Of 1425 participants, 15 pregnant women (1.05%, 95% CI: 0.64%-1.73%) were positive for HBsAg, 41 women (2.88%, 95% CI: 2.10%-3.88%) were positive for HBcAb, and 5 women (0.35%, 95% CI: 0.15% –0.82%) had HBV viremia with genotype D, sub-genotype D3 and subtype ayw2. One of the viremic samples was positive for HBcAb but negative for HBsAg, which is indicative of an occult HBV infection. HBsAg seroprevalence was higher among pregnant women aged 20 to 29 years, women in the third trimester of pregnancy, residents of Khormuj city, Afghan immigrants, illiterate women, and pregnant women with a history of tattoo and HBV vaccination. The highest rate of HBcAb seroprevalence was observed in residents of Borazjan city, Turk ethnicity, the age group >39 years, and those women with more parities and a history of abortion. Nevertheless, HBV seroprevalence among pregnant women was not statistically associated with these variables. In contrast, HBcAb seropositivity was significantly associated with the history of tattoo (P = 0.018). According to mutations analyses, seven amino acid substitutions in the HBsAg, one point mutation in the pre-C region, and five points mutations in the BCP region were detected. Besides, the BCP mutations caused amino acid substitutions in the X protein. Of note, the conversion of Ala → Val at amino acid 168 (A168V) and Thr → Pro at amino acid 127 (T127P) were detected in HBsAg of the occult HBV strain. Conclusion These results indicate a relatively low prevalence of HBV infection among pregnant women in the South of Iran, while tattooing is a risk factor for exposure to HBV infection. Moreover, all of the HBV-positive pregnant women were asymptomatic and unaware of their infection. Therefore, routine screening for HBV markers during pregnancy, appropriate treatment of HBV-infected women, and HBV vaccination are recommended to decrease mother-to-child transmission of HBV.
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30
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Brown R, Goulder P, Matthews PC. Sexual Dimorphism in Chronic Hepatitis B Virus (HBV) Infection: Evidence to Inform Elimination Efforts. Wellcome Open Res 2022; 7:32. [PMID: 36212217 PMCID: PMC9520633 DOI: 10.12688/wellcomeopenres.17601.2] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/19/2022] [Indexed: 08/27/2024] Open
Abstract
Sexual dimorphism in infectious diseases refers to the different infection susceptibilities and outcomes between males and females, and has been described for many pathogens, including hepatitis B virus (HBV). HBV is a substantial global health problem, with close to 300 million people chronically infected, and accounting for a million deaths each year, with an urgent need for enhanced interventions to support progress towards elimination goals. Sexual dimorphism has a strong influence in HBV infection, with males more likely to be exposed, to develop chronic infection, and to suffer from complications including cirrhosis and hepatocellular carcinoma (HCC) compared to females. Different outcomes are driven by differential immune responses, sexual dimorphism of the liver, and androgen response elements in the HBV genome. The impact of sex may also vary with age, with changes at puberty and influences of menarche, pregnancy and menopause in females. In addition, gender has complex influences on education, beliefs, behaviour and access to / engagement with healthcare services, which may contribute to differences in diagnosis and treatment. Interplay between these complex factors, alongside other attributes of host, virus and the environment, accounts for different outcomes of infection. However, gaps remain in our understanding of sexual dimorphism in HBV, and little effort has previously been made to harness this knowledge for translational gains. In this review, we assimilate human and animal data to consider the mechanism, outcomes and impact of sexual dimorphism, and consider how these insights can be used to inform advances in surveillance, treatment and prevention for HBV infection.
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Affiliation(s)
- Robin Brown
- Harris Manchester College, University of Oxford, Oxford, Oxon, OX1 3TD, UK
| | - Philip Goulder
- Department of Paediatrics, University of Oxford, Oxford, Oxon, OX1 3SY, UK
| | - Philippa C. Matthews
- Harris Manchester College, University of Oxford, Oxford, Oxon, OX1 3TD, UK
- The Francis Crick Institute, London, London, NW1 1AT, UK
- Division of Infection and Immunity, University College London, London, WC1E 6BT, UK
- Department of Infectious Diseases, University College London Hospital, London, NW1 2BU, UK
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31
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Brown R, Goulder P, Matthews PC. Sexual Dimorphism in Chronic Hepatitis B Virus (HBV) Infection: Evidence to Inform Elimination Efforts. Wellcome Open Res 2022; 7:32. [PMID: 36212217 PMCID: PMC9520633 DOI: 10.12688/wellcomeopenres.17601.1] [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] [Accepted: 01/20/2022] [Indexed: 09/06/2024] Open
Abstract
Sexual dimorphism in infectious diseases refers to the different infection susceptibilities and outcomes between males and females, and has been described for many pathogens, including hepatitis B virus (HBV) infection. HBV is a substantial global health problem, with close to 300 million people infected, and accounting for a million deaths each year, with an urgent need for enhanced interventions to support progress towards elimination goals. Sexual dimorphism has a strong influence in HBV infection, with males more likely to be exposed, to develop chronic infection, and to suffer from complications including cirrhosis and hepatocellular carcinoma (HCC) compared to females. Different outcomes are driven by differential immune responses, sexual dimorphism of the liver, and androgen response elements in the HBV genome. The impact of sex may also vary with age, with changes at puberty and influences of menarche, pregnancy and menopause in females. In addition, gender has complex influences on education, beliefs, behaviour and access to / engagement with healthcare services, which may contribute to differences in diagnosis and treatment. Interplay between these complex factors, alongside other attributes of host, virus and the environment, accounts for different outcomes of infection. However, gaps remain in our understanding of sexual dimorphism in HBV, and little effort has previously been made to harness this knowledge for translational gains. In this review, we assimilate human and animal data to consider the mechanism, outcomes and impact of sexual dimorphism, considering how these insights can be used to inform advances in surveillance, treatment and prevention for HBV infection.
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Affiliation(s)
- Robin Brown
- Harris Manchester College, University of Oxford, Oxford, Oxon, OX1 3TD, UK
| | - Philip Goulder
- Department of Paediatrics, University of Oxford, Oxford, Oxon, OX1 3SY, UK
| | - Philippa C. Matthews
- Harris Manchester College, University of Oxford, Oxford, Oxon, OX1 3TD, UK
- The Francis Crick Institute, London, London, NW1 1AT, UK
- Division of Infection and Immunity, University College London, London, WC1E 6BT, UK
- Department of Infectious Diseases, University College London Hospital, London, NW1 2BU, UK
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32
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Song MJ. Postpartum Hepatic Flares in Immune-Tolerant Pregnant Patients with Chronic Hepatitis B Virus Infection. Gut Liver 2022; 16:5-7. [PMID: 35027508 PMCID: PMC8761921 DOI: 10.5009/gnl210472] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
Affiliation(s)
- Myeong Jun Song
- Division of Hepatology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea
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33
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Dad N, Buhmaid S, Mulik V. Vaccination in pregnancy - The when, what and how? Eur J Obstet Gynecol Reprod Biol 2021; 265:1-6. [PMID: 34403876 DOI: 10.1016/j.ejogrb.2021.08.009] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2021] [Revised: 07/24/2021] [Accepted: 08/05/2021] [Indexed: 01/07/2023]
Abstract
Immunization is a fundamental component of preventive healthcare. This gain special significance in pregnancy. Maternal antigen-specific IgG, is actively transported across the placenta during pregnancy. This significantly, contributes to infant immunity in the first few months of life. Vaccination during pregnancy has the potential to indirectly protect the most vulnerable infants during the first few months of life, when vaccine responses are generally poor and it is difficult to achieve rapid protection through immunization. This is especially relevant when there is prior exposure to infection in woman or vaccine administration. A vaccine given during pregnancy in these women would result in a booster response and a relatively high level of IgG protecting their children in initial few months of life. Passive antibody transfer from mother to fetus can protect fetuses from infection until their own immunization schedule is initiated. Lack of administration of appropriate vaccination to women during pregnancy lead to an increase in maternal and fetal morbidity and mortality from preventable infections like influenza, pertussis. Various preventable infections can lead to intensive care unit admission for mothers, preterm birth, and low birth weight babies. Recent covid pandemic has brought issue of vaccine use in pregnancy at forefront of all expectant mothers. Immunization with inactivated virus, bacterial vaccine and toxoids showed no evidence of adverse fetal effects. As a rule, live attenuated vaccines are not recommended in pregnancy. This paper gives snapshot of all vaccines, which can be used in pregnancy along with brief details regards various bacterial and viral infections , their common clinical features and effects on pregnancy outcome as well as fetus. This is will provide a useful guide for healthcare providers.
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Affiliation(s)
- Nimra Dad
- Sidra Medicine, PO Box 26999, Education city, Doha, Qatar
| | - Sara Buhmaid
- Sidra Medicine, PO Box 26999, Education city, Doha, Qatar
| | - Varsha Mulik
- Sidra Medicine, PO Box 26999, Education city, Doha, Qatar.
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34
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Huang M, Gao Y, Yin X, Zhang X, Hao Y, Hu J, Liu Z. Characterization of T cell immunity in chronic hepatitis B virus-infected mothers with postpartum alanine transaminase flare. BMC Infect Dis 2021; 21:922. [PMID: 34488681 PMCID: PMC8422606 DOI: 10.1186/s12879-021-06634-2] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2021] [Accepted: 08/25/2021] [Indexed: 12/27/2022] Open
Abstract
BACKGROUND Postpartum alanine transaminase (ALT) flares occur frequently in chronic hepatitis B virus (HBV)-infected mothers with antepartum antiviral therapy (AVT). We aimed to characterize the T cell immunity in HBV-infected mothers experiencing postpartum ALT flares. METHODS Twenty HBV-infected pregnant women who received AVT at 26-28 weeks of gestation were enrolled and followed up until 15-18 weeks postpartum. Among the 20 HBV-infected pregnant women, 6 experienced postpartum ALT flare (AF mothers), while 14 did not (NAF mothers). T lymphocyte phenotypes and functions were analyzed using flow cytometry. RESULTS Compared to NAF mothers, the quantitative HBsAg levels in AF mothers decreased significantly at 6-8 or 15-18 weeks postpartum. Significant differences in HBeAg levels between these groups were only found at delivery. Regulatory T cell (Treg) numbers in AF mothers were lower than those of NAF mothers before AVT; however, there were no significant differences in Treg numbers at other follow-up points. Expression of other T cell phenotypes were similar between the two groups. T cells in AF mothers produced more pro-inflammatory cytokines (IFN-γ, IL-21, TNF-α, IL-2) or less anti-inflammatory cytokine (IL-10) than those in NAF mothers before, during, or after antiviral treatment. The ratio of IFN-γ to IL-10 producing by CD4+ T cells or CD8+ T cells was higher in AF mothers than that in NAF mothers during pregnancy or after delivery. CONCLUSIONS The characteristics of T cell immunity was distinct between mothers with postpartum ALT flare and those without ALT flare from pregnancy to postpartum, which indicated that T cell immunity might get involved in postpartum ALT flare.
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Affiliation(s)
- Meiting Huang
- Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.,Department of Infectious Diseases, Huizhou Third People's Hospital, Guangzhou Medical University, Huizhou, 516002, China
| | - Yunfei Gao
- Department of Obstetrics and Gynaecology, Zengcheng Branch of Nanfang Hospital, Southern Medical University, Guangzhou, 511340, China
| | - Xueru Yin
- Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China
| | - Xuelian Zhang
- Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China
| | - Yaohua Hao
- Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China
| | - Jing Hu
- Department of Nosocomial Infection Administration, Zhujiang Hospital, Southern Medical University, Guangzhou, 510280, China
| | - Zhihua Liu
- Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China. .,Liver Diseases Center, Shenzhen Hospital of Southern Medical University, Shenzhen, 518000, China.
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35
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Zhang X, Zou H, Chen Y, Zhang H, Tian R, Meng J, Zhu Y, Guo H, Dai E, Zhu B, Liu Z, Jin Y, Li Y, Feng L, Zhuang H, Pan CQ, Li J, Duan Z. The effects of increased dose of hepatitis B vaccine on mother-to-child transmission and immune response for infants born to mothers with chronic hepatitis B infection: a prospective, multicenter, large-sample cohort study. BMC Med 2021; 19:148. [PMID: 34253217 PMCID: PMC8276424 DOI: 10.1186/s12916-021-02025-1] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/27/2021] [Accepted: 06/04/2021] [Indexed: 01/13/2023] Open
Abstract
BACKGROUND Appropriate passive-active immunoprophylaxis effectively reduces mother-to-child transmission (MTCT) of hepatitis B virus (HBV), but the immunoprophylaxis failure was still more than 5% under the current strategy. The study objective was to investigate the effects of high dose of HB vaccine on MTCT and immune response for infants born to hepatitis B surface antigen (HBsAg)-positive mothers. METHODS This was a prospective, multicenter, large-sample cohort study in four sites of China, and 955 pairs of HBsAg-positive mothers and their infants were enrolled in our investigation. The infants were given 10 μg or 20 μg HB vaccine (at age 0, 1, and 6 months) plus HB immunoglobulin (at age 0 and 1 month). Serum HBsAg, antibody to HBsAg (anti-HBs), and/or HBV DNA levels in the infants were determined at age 12 months. The safety of 20 μg HB vaccine was evaluated by adverse events and observing the growth indexes of infants. RESULTS Thirteen of 955 infants were HBsAg-positive at 12 months. Stratification analysis showed that immunoprophylaxis failure rates in the 20 μg group were not significantly different from the 10 μg group, whatever maternal HBV load was high or not. But the high dose of HB vaccine significantly reduced low-response rate (anti-HBs 10-100 IU/L) (P = 0.002) and middle-response rate (anti-HBs 100-1000 IU/L) (P = 0.022) and improved high-response rate (anti-HBs ≥ 1000 IU/L) (P < 0.0001) in infants born to mothers with HBV DNA < 5 log10 IU/mL. For infants born to mothers with HBV DNA ≥ 5 log10 IU/mL, 20 μg HB vaccine did not present these above response advantages. The 20 μg HB vaccine showed good safety for infants. CONCLUSIONS The 20 μg HB vaccine did not further reduce immunoprophylaxis failure of infants from HBsAg-positive mothers, but increased the high-response and decreased low-response rates for infants born to mothers with HBV DNA < 5 log10 IU/mL. TRIAL REGISTRATION Chinese Clinical Trial Registry, ChiCTR-PRC-09000459.
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Affiliation(s)
- Xiaohui Zhang
- Artificial Liver Treatment Center, Beijing Youan Hospital, Capital Medical University, Beijing, China.,Beijing Municipal Key Laboratory of Liver Failure and Artificial Liver Treatment Research, Beijing, China
| | - Huaibin Zou
- Artificial Liver Treatment Center, Beijing Youan Hospital, Capital Medical University, Beijing, China.,Beijing Municipal Key Laboratory of Liver Failure and Artificial Liver Treatment Research, Beijing, China
| | - Yu Chen
- Artificial Liver Treatment Center, Beijing Youan Hospital, Capital Medical University, Beijing, China.,Beijing Municipal Key Laboratory of Liver Failure and Artificial Liver Treatment Research, Beijing, China
| | - Hua Zhang
- Department of Obstetrics and Gynecology, Beijing Youan Hospital, Capital Medical University, Beijing, China
| | - Ruihua Tian
- Department of Obstetrics and Gynecology, Beijing Youan Hospital, Capital Medical University, Beijing, China
| | - Jun Meng
- Department of Obstetrics and Gynecology, Beijing Youan Hospital, Capital Medical University, Beijing, China
| | - Yunxia Zhu
- Department of Obstetrics and Gynecology, Beijing Youan Hospital, Capital Medical University, Beijing, China
| | - Huimin Guo
- Artificial Liver Treatment Center, Beijing Youan Hospital, Capital Medical University, Beijing, China
| | - Erhei Dai
- Department of Liver Diseases, The Fifth Hospital of Shijiazhuang, Shijiazhuang, China
| | - Baoshen Zhu
- Department of Liver Diseases, The Fifth Hospital of Shijiazhuang, Shijiazhuang, China
| | | | - Yanxia Jin
- Tongliao Infective Disease Hospital, Tongliao, China
| | - Yujie Li
- Department of Obstetrics and Gynecology, Taiyuan No. 3 Hospital, Taiyuan, China
| | - Liping Feng
- Department of Obstetrics and Gynecology, Taiyuan No. 3 Hospital, Taiyuan, China
| | - Hui Zhuang
- Department of Microbiology and Center of Infectious Disease, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China
| | - Calvin Q Pan
- Division of Gastroenterology and Hepatology, Department of Medicine, New York University, Langone Health, NYU Grossman School of Medicine, New York, USA.
| | - Jie Li
- Department of Microbiology and Center of Infectious Disease, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China.
| | - Zhongping Duan
- Artificial Liver Treatment Center, Beijing Youan Hospital, Capital Medical University, Beijing, China. .,Beijing Municipal Key Laboratory of Liver Failure and Artificial Liver Treatment Research, Beijing, China.
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36
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Vachon A, Osiowy C. Novel Biomarkers of Hepatitis B Virus and Their Use in Chronic Hepatitis B Patient Management. Viruses 2021; 13:951. [PMID: 34064049 PMCID: PMC8224022 DOI: 10.3390/v13060951] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2021] [Revised: 05/17/2021] [Accepted: 05/18/2021] [Indexed: 12/15/2022] Open
Abstract
Even though an approved vaccine for hepatitis B virus (HBV) is available and widely used, over 257 million individuals worldwide are living with chronic hepatitis B (CHB) who require monitoring of treatment response, viral activity, and disease progression to reduce their risk of HBV-related liver disease. There is currently a lack of predictive markers to guide clinical management and to allow treatment cessation with reduced risk of viral reactivation. Novel HBV biomarkers are in development in an effort to improve the management of people living with CHB, to predict disease outcomes of CHB, and further understand the natural history of HBV. This review focuses on novel HBV biomarkers and their use in the clinical setting, including the description of and methodology for quantification of serum HBV RNA, hepatitis B core-related antigen (HBcrAg), quantitative hepatitis B surface antigen (qHBsAg), including ultrasensitive HBsAg detection, quantitative anti-hepatitis B core antigen (qAHBc), and detection of HBV nucleic acid-related antigen (HBV-NRAg). The utility of these biomarkers in treatment-naïve and treated CHB patients in several clinical situations is further discussed. Novel HBV biomarkers have been observed to provide critical clinical information and show promise for improving patient management and our understanding of the natural history of HBV.
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Affiliation(s)
- Alicia Vachon
- Department of Medical Microbiology and Infectious Diseases, University of Manitoba, Winnipeg, MB R3E 0J9, Canada;
- National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, MB R3E 3R2, Canada
| | - Carla Osiowy
- Department of Medical Microbiology and Infectious Diseases, University of Manitoba, Winnipeg, MB R3E 0J9, Canada;
- National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, MB R3E 3R2, Canada
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37
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Chen X, Zhou Q, Dong S, Wang S, Liu R, Wu X, Li S. Multiple Cross Displacement Amplification Linked with Nanoparticles-Based Lateral Flow Biosensor in Screening of Hepatitis B Virus in Clinical Application. Infect Drug Resist 2021; 14:1219-1229. [PMID: 33790592 PMCID: PMC8007573 DOI: 10.2147/idr.s297645] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2020] [Accepted: 03/09/2021] [Indexed: 12/16/2022] Open
Abstract
Background Hepatitis B virus (HBV) is a common pathogen that predominantly causes severe liver disease, and remains one of a huge challenge worldwide, especially in many resource-constrained areas. Developing a low-cost, sensitive, specific, and rapid approach for screening HBV is critical for its treatment and prevention. In the current study, a novel molecular detection approach, multiple cross displacement amplification (MCDA) coupled with polymer nanoparticle-based lateral flow biosensor (MCDA-LFB), was applied for detection of HBV in blood samples. Methods HBV standard substance and clinical donor serum samples were collected and used for the establishment and confirmation of the HBV-MCDA-LFB assay. A set of 10 MCDA primers was designed according to HBV-specific gene S. The HBV-MCDA-LFB assay conditions, including genomic template concentration, MCDA reaction temperature and time were optimized. The sensitivity and specificity of the HBV-MCDA -LFB assay were evaluated in this report. The HBV-MCDA-LFB assay was applied to detect the HBV agent from clinical samples. Results The HBV-MCDA primers based on the S gene were valid for establishment of MCDA assay. The HBV-MCDA reaction with optimized conditions could be carried out at a constant temperature 64°C for 35 min. The whole process, including sample preparation (5 min), genomic template extraction (~30 min), MCDA amplification (35 min), and LFB reading (~2 min), could be completed within 80 min. The sensitivity of this assay was 5 IU per reaction. The specificity was 100% for HBV-MCDA-LFB assay. Conclusion These results confirmed that the HBV-MCDA-LFB is a low-cost, sensitive, specific, simple, and rapid method for detecting HBV agents. This technique has great potential to develop a point-of-care testing (POCT) method in clinical practice, especially in endemic and resource-constrained regions.
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Affiliation(s)
- Xu Chen
- The Second Clinical College, Guizhou University of Traditional Chinese Medicine, Guiyang, Guizhou, 550003, People's Republic of China.,Central Laboratory of the Second Affiliated Hospital, Guizhou University of Traditional Chinese Medicine, Guiyang, Guizhou, 550003, People's Republic of China
| | - Qingxue Zhou
- Clinical Laboratory, Hangzhou Women's Hospital, Hangzhou, Zhejiang, 310008, People's Republic of China
| | - Shilei Dong
- Department of Clinical Laboratory, Zhejiang Hospital, Hangzhou, Zhejiang, 310013, People's Republic of China
| | - Shuoshi Wang
- Central Laboratory of the Second Affiliated Hospital, Guizhou University of Traditional Chinese Medicine, Guiyang, Guizhou, 550003, People's Republic of China
| | - Rui Liu
- Central Laboratory of the Second Affiliated Hospital, Guizhou University of Traditional Chinese Medicine, Guiyang, Guizhou, 550003, People's Republic of China
| | - Xueli Wu
- Central Laboratory of the Second Affiliated Hospital, Guizhou University of Traditional Chinese Medicine, Guiyang, Guizhou, 550003, People's Republic of China
| | - Shijun Li
- Laboratory of Bacterial Infectious Disease of Experimental Centre, Guizhou Provincial Centre for Disease Control and Prevention, Guiyang, Guizhou, 550004, People's Republic of China
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38
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Kanbe A, Ishikawa T, Hara A, Suemizu H, Nanizawa E, Tamaki Y, Ito H. Novel hepatitis B virus infection mouse model using herpes simplex virus type 1 thymidine kinase transgenic mice. J Gastroenterol Hepatol 2021; 36:782-789. [PMID: 32515517 DOI: 10.1111/jgh.15142] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/05/2020] [Revised: 04/24/2020] [Accepted: 06/07/2020] [Indexed: 12/12/2022]
Abstract
BACKGROUND AND AIM The chronicity of hepatitis B virus (HBV) infection is the result of impaired HBV-specific immune responses that cannot eliminate or cure the infected hepatocytes efficiently. Previous studies have used immunodeficient mice such as herpes simplex virus type 1 thymidine kinase NOD/Scid/IL2Rrnull (HSV-TK-NOG) mice. However, it is difficult to analyze the immune response in the previous models. In the present study, we established a novel HBV infection model using herpes simplex virus type 1 thymidine kinase (HSV-TK) mice in which the host immune system was not impaired. METHODS Herpes simplex virus type 1 thymidine kinase mice were injected intraperitoneally with ganciclovir (GCV). Seven days after GCV injection, GCV-treated mice were transplanted with 1 × 106 hepatocytes from HBV-transgenic (HBV-Tg) mice. RESULTS Serum alanine aminotransferase levels in HSV-TK mice increased 1 and 2 weeks after GCV injection. The number and viability of hepatocytes from the whole liver of HBV-Tg mice significantly increased using digestion medium containing liberase. Hepatitis B surface antigen (HBsAg)-positive areas in the liver tissue were observed for at least 20 weeks after HBsAg-positive hepatocyte transplantation. In addition, we measured HBsAg in the serum after transplantation. HBsAg levels in HBV-Tg hepatocyte-replaced mice increased 4 weeks after transplantation. Furthermore, we examined the immune response in HSV-TK mice. The increase in hepatitis B surface antibody levels in replaced mice was maintained for 20 weeks. Also, interferon-γ-producing cells were increased in non-replaced mice. CONCLUSIONS A novel HBV infection mouse model will help to understand the mechanisms of HBV tolerance similar to human chronic HBV-infected patients and can be used to develop a new strategy to treat chronic HBV infection.
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Affiliation(s)
- Ayumu Kanbe
- Department of Informative Clinical Medicine, Gifu University Graduate School of Medicine, Gifu City, Japan
| | - Tetsuya Ishikawa
- Department of Radiological and Medical Laboratory Sciences, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Akira Hara
- Department of Tumor Pathology, Gifu University Graduate School of Medicine, Gifu City, Japan
| | - Hiroshi Suemizu
- Department of Laboratory Animal Research, Central Institute for Experimental Animals, Kawasaki, Japan
| | - Eri Nanizawa
- Department of Radiological and Medical Laboratory Sciences, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Yuki Tamaki
- Department of Radiological and Medical Laboratory Sciences, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Hiroyasu Ito
- Department of Informative Clinical Medicine, Gifu University Graduate School of Medicine, Gifu City, Japan
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Dawson-Hahn EE, Pidaparti V, Hahn W, Stauffer W. Global mobility, travel and migration health: clinical and public health implications for children and families. Paediatr Int Child Health 2021; 41:3-11. [PMID: 33769218 DOI: 10.1080/20469047.2021.1876821] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
Abstract
Exponential growth of the world's population combined with increased travel has dramatically increased the spread of infectious diseases. Although there has been significant focus on migration, the major contributors to the transmission of communicable diseases are travel and tourism not migration. Given that children represent up to 10% of international travellers, it is critical to the health of all age groups to ensure that tailored guidance for children is considered in public health policy and guidelines, and pandemic responses. To further support pandemic preparedness, public health systems need to strengthen ties with communities and health systems. In addition, travel and migration issues need to be included as core competencies in medical education. Ensuring that clinicians who care for children have knowledge of travel and migration health will foster a better health outcome in an increasingly mobile population at risk of emerging infectious diseases.Abbreviations CDC: Centers for Disease Control and Prevention; DGMQ: CDC Division of Global Migration and Quarantine; EID: emerging infectious diseases; EU: European Union; VFR: visiting friends and relatives; IOM: United Nations International Organization for Migration; LPR: lawful permanent resident; US: United States of America; WHO: World Health Organization.
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Affiliation(s)
- Elizabeth E Dawson-Hahn
- Division of General Paediatrics, Department of Pediatrics, University of Washington, Seattle, WA, USA.,Center for Child Health, Behavior and Development, Seattle Children's Research Institute, Seattle, WA, USA
| | - Vaidehi Pidaparti
- Division of General Paediatrics, Department of Pediatrics, University of Washington, Seattle, WA, USA
| | - William Hahn
- Department of Medicine, Division of Allergy & Infectious Diseases, University of Washington, Seattle, WA, USA
| | - William Stauffer
- Division of Infectious Disease, Departments of Medicine and Pediatrics, University of Minnesota, Minneapolis, MN, USA.,Program for Human Migration and Health, Center for Social Responsibility and Global Health, University of Minnesota, Minneapolis, MN, USA
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40
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Zeleke ED, Assefa DG, Joseph M, Bekele D, Tesfahunei HA, Getachew E, Manyazewal T. Tenofovir disoproxil fumarate for prevention of mother-to-child transmission of hepatitis B virus: A systematic review and meta-analysis of randomised control trials. Rev Med Virol 2021; 31:1-16. [PMID: 33483986 DOI: 10.1002/rmv.2216] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2020] [Revised: 12/19/2020] [Accepted: 12/21/2020] [Indexed: 02/06/2023]
Abstract
Hepatitis B virus (HBV) infection caused by mother-to-child transmission (MTCT) continues to pose challenges to global health. This study aimed to assess the efficacy and safety of tenofovir disoproxil fumarate (TDF) for preventing HBV MTCT. PubMed and the Cochrane Central Register of Controlled Trials were searched through August 2020. Randomised controlled trials (RCTs) were selected that evaluated the efficacy and safety of TDF for preventing MTCT of HBV compared with the standard of care, placebo or other HBV therapies. The primary outcomes were HBV MTCT rate and maternal HBV DNA level. Secondary outcomes were infant and maternal safety outcomes. The review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Guidelines, and prospectively registered on PROSPERO (CRD42020186275). Of 240 citations, three RCTs that involved 651 participants were included. The pooled result showed that TDF can reduce the risk of HBV MTCT after 6 months postpartum by 80% (risk ratio [RR] 0.2, 95% confidence interval [CI 0.06-0.7], n = 584) with low heterogeneity (I2 = 0%). TDF demonstrated HBV DNA suppression at delivery, though there was heterogeneity among individual studies (RR 0.13, 95% CI [0.08-0.20] and (RR 0.36, 95% CI [0.27-0.49]). Maternal and infant safety outcomes were comparable among treated and untreated mothers and infants born to them. The quality of evidence varied from high to very low. There is evidence that TDF effectively interrupted MTCT of HBV and suppressed HBV DNA level. Available studies on safety are very limited and heterogeneous, emphasising the need for additional RCTs with complete safety indicators.
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Affiliation(s)
- Eden Dagnachew Zeleke
- Department of Center for Innovative Drug Development and Therapeutic Trials for Africa (CDT-Africa), College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia.,Department of Midwifery, College of Health and Medical Science, Bule Hora University, Bule Hora, Ethiopia
| | - Dawit Getachew Assefa
- Department of Center for Innovative Drug Development and Therapeutic Trials for Africa (CDT-Africa), College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia.,Department of Nursing, College of Health Science and Medicine, Dilla University, Dilla, Ethiopia
| | - Michele Joseph
- Department of Center for Innovative Drug Development and Therapeutic Trials for Africa (CDT-Africa), College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia
| | - Delayehu Bekele
- Department of Center for Innovative Drug Development and Therapeutic Trials for Africa (CDT-Africa), College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia.,Department of Obstetrics and Gynecology, Saint Paul's Hospital Millennium Medical College, Addis Ababa, Ethiopia
| | - Hanna Amanuel Tesfahunei
- Department of Center for Innovative Drug Development and Therapeutic Trials for Africa (CDT-Africa), College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia.,Department of Public Health, Hager Biomedical Research Institute, Asmara, Eritrea
| | - Emnet Getachew
- Department of Center for Innovative Drug Development and Therapeutic Trials for Africa (CDT-Africa), College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia.,Department of Public Health, Arsi University, Asella, Ethiopia
| | - Tsegahun Manyazewal
- Department of Center for Innovative Drug Development and Therapeutic Trials for Africa (CDT-Africa), College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia
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41
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Efficacy of Nucleotide/Nucleoside Analogues and Hepatitis B Immunoglobulin Therapy in Blocking Mother-to-Child Transmission of Hepatitis B in an Eastern Chinese Group. Infect Dis Obstet Gynecol 2020; 2020:4305950. [PMID: 33380780 PMCID: PMC7759418 DOI: 10.1155/2020/4305950] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2020] [Revised: 10/19/2020] [Accepted: 11/24/2020] [Indexed: 11/24/2022] Open
Abstract
The objective of this study was to investigate the efficacy and potential side-effects of nucleotide/nucleoside analogues and hepatitis B immunoglobulin injection of newborns in blocking mother-to-child transmission of hepatitis B virus in the middle and late pregnancy period. 238 cases of enrolled pregnant women were divided into the Telbivudine group, the Tenofovir group, the Lamivudine group, and the hepatitis B immunoglobulin (HBIG) group. Enrolled patients received corresponding therapies. Clinical and laboratory data were collected. Results showed that the levels of HBV DNA of the enrolled pregnant women in the Telbivudine, Tenofovir, and Lamivudine groups decreased rapidly after 12 weeks of drug intervention compared with those in the control. HBsAg positive rate in newborns and in children 24 weeks after birth was 0/60, 0/60, 0/60, 3/30, and 11/28 in the Telbivudine, Tenofovir, Lamivudine, HBIG, and control groups, respectively. No significant side-effects were identified after following up to 12 months after birth. Our results show that routine HBV vaccine plus HBIG injections is insufficient in blocking mother-to-child HBV transmission. Administration of nucleotide/nucleoside analogues or HBIG at pregnancy is suggested to maximize the blocking of vertical HBV transmission.
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D'souza S, Lau KCK, Coffin CS, Patel TR. Molecular mechanisms of viral hepatitis induced hepatocellular carcinoma. World J Gastroenterol 2020; 26:5759-5783. [PMID: 33132633 PMCID: PMC7579760 DOI: 10.3748/wjg.v26.i38.5759] [Citation(s) in RCA: 146] [Impact Index Per Article: 29.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/14/2020] [Revised: 09/03/2020] [Accepted: 09/17/2020] [Indexed: 02/06/2023] Open
Abstract
Chronic infection with viral hepatitis affects half a billion individuals worldwide and can lead to cirrhosis, cancer, and liver failure. Liver cancer is the third leading cause of cancer-associated mortality, of which hepatocellular carcinoma (HCC) represents 90% of all primary liver cancers. Solid tumors like HCC are complex and have heterogeneous tumor genomic profiles contributing to complexity in diagnosis and management. Chronic infection with hepatitis B virus (HBV), hepatitis delta virus (HDV), and hepatitis C virus (HCV) are the greatest etiological risk factors for HCC. Due to the significant role of chronic viral infection in HCC development, it is important to investigate direct (viral associated) and indirect (immune-associated) mechanisms involved in the pathogenesis of HCC. Common mechanisms used by HBV, HCV, and HDV that drive hepatocarcinogenesis include persistent liver inflammation with an impaired antiviral immune response, immune and viral protein-mediated oxidative stress, and deregulation of cellular signaling pathways by viral proteins. DNA integration to promote genome instability is a feature of HBV infection, and metabolic reprogramming leading to steatosis is driven by HCV infection. The current review aims to provide a brief overview of HBV, HCV and HDV molecular biology, and highlight specific viral-associated oncogenic mechanisms and common molecular pathways deregulated in HCC, and current as well as emerging treatments for HCC.
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Affiliation(s)
- Simmone D'souza
- Department of Microbiology, Immunology, and Infectious Diseases, Cumming School of Medicine, University of Calgary, Calgary T2N 1N4, AB, Canada
| | - Keith CK Lau
- Department of Microbiology, Immunology, and Infectious Diseases, Cumming School of Medicine, University of Calgary, Calgary T2N 1N4, AB, Canada
| | - Carla S Coffin
- Department of Microbiology, Immunology, and Infectious Diseases, Cumming School of Medicine, University of Calgary, Calgary T2N 1N4, AB, Canada
| | - Trushar R Patel
- Department of Microbiology, Immunology, and Infectious Diseases, Cumming School of Medicine, University of Calgary, Calgary T2N 1N4, AB, Canada
- Department of Chemistry and Biochemistry, Alberta RNA Research and Training Institute, University of Lethbridge, Lethbridge T1K3M4, AB, Canada
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43
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Rybicka M, Bielawski KP. Recent Advances in Understanding, Diagnosing, and Treating Hepatitis B Virus Infection. Microorganisms 2020; 8:E1416. [PMID: 32942584 PMCID: PMC7565763 DOI: 10.3390/microorganisms8091416] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2020] [Revised: 09/08/2020] [Accepted: 09/11/2020] [Indexed: 02/06/2023] Open
Abstract
Chronic hepatitis B virus (HBV) infection affects 292 million people worldwide and is associated with a broad range of clinical manifestations including cirrhosis, liver failure, and hepatocellular carcinoma (HCC). Despite the availability of an effective vaccine HBV still causes nearly 900,000 deaths every year. Current treatment options keep HBV under control, but they do not offer a cure as they cannot completely clear HBV from infected hepatocytes. The recent development of reliable cell culture systems allowed for a better understanding of the host and viral mechanisms affecting HBV replication and persistence. Recent advances into the understanding of HBV biology, new potential diagnostic markers of hepatitis B infection, as well as novel antivirals targeting different steps in the HBV replication cycle are summarized in this review article.
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Affiliation(s)
- Magda Rybicka
- Department of Molecular Diagnostics, Intercollegiate Faculty of Biotechnology, University of Gdansk and Medical University of Gdansk, Abrahama 58, 80-307 Gdansk, Poland;
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44
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Huang H, Xu C, Liu L, Chen L, Zhu X, Chen J, Feng J, Chen T, Xu B, Yang J, Xu B, Pan M, Dai Y, Hu Y, Zhou YH. Increased protection of earlier use of immunoprophylaxis in preventing perinatal transmission of hepatitis B virus. Clin Infect Dis 2020; 73:e3317-e3323. [PMID: 32634824 DOI: 10.1093/cid/ciaa898] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2020] [Accepted: 06/24/2020] [Indexed: 12/16/2022] Open
Abstract
BACKGROUND Passive-active immunoprophylaxis against mother-to-child transmission (MTCT) of hepatitis B virus (HBV) recommends administer hepatitis B immunoglobulin (HBIG) and birth dose hepatitis B vaccine in infants within 12 or 24 hours after birth. With this protocol, MTCT of HBV still occurs in 5-10% infants of HBV-infected mothers with positive hepatitis B e antigen (HBeAg). METHODS The present study aimed to investigate whether earlier administration of HBIG and hepatitis B vaccine after birth can further increase the protection efficacy. RESULTS Totally, 1140 HBV-infected pregnant women were enrolled, and 982 infants (9 twins) of 973 mothers were finally followed up at 9.6 ± 1.9 months age. HBIG and birth dose vaccine were administered in newborn infants with a median 0.17 hour (0.02-1.0) after birth. The overall rate of MTCT was 0.9% (9/982), with none (0%) of 607 infants of HBeAg-negative mothers and 9 (2.4%) of 375 infants of HBeAg-positive mothers. All nine HBV-infected infants were born to mothers with HBV DNA >2.75×106 IU/ml. Maternal HBV DNA levels >1×106 IU/ml was an independent risk factor (OR = 10.627, 95% CI: 2.135-+∞) for immunoprophylaxis failure. CONSLUSIONS Earlier use (within one hour after birth) of HBIG and hepatitis B vaccine can provide better protection efficacy against MTCT of HBV.
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Affiliation(s)
- Hongyu Huang
- Department of Experimental Medicine and Jiangsu Key Laboratory for Molecular Medicine, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, China
| | - Chenyu Xu
- Department of Obstetrics and Gynecology, Zhenjiang Fourth People's Hospital, Zhenjiang, China
| | - Lanhua Liu
- Department of Obstetrics and Gynecology, Taixing People's Hospital, Taizhou, China
| | - Liping Chen
- Department of Obstetrics and Gynecology, Nantong First People's Hospital, Nantong, China
| | - Xiaoqin Zhu
- Department of Obstetrics and Gynecology, Huai'an Maternal and Children's Hospital, Huai'an, China
| | - Jie Chen
- Department of Obstetrics and Gynecology, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, China
| | - Jing Feng
- Department of Obstetrics and Gynecology, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, China
| | - Tingmei Chen
- Department of Obstetrics and Gynecology, Zhenjiang Fourth People's Hospital, Zhenjiang, China
| | - Biao Xu
- Department of Obstetrics and Gynecology, Taixing People's Hospital, Taizhou, China
| | - Jishi Yang
- Department of Obstetrics and Gynecology, Taixing People's Hospital, Taizhou, China
| | - Biyun Xu
- Department of Biostatistics, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, China
| | - Mingjie Pan
- Department of Experimental Medicine and Jiangsu Key Laboratory for Molecular Medicine, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, China
| | - Yimin Dai
- Department of Obstetrics and Gynecology, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, China
| | - Yali Hu
- Department of Obstetrics and Gynecology, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, China
| | - Yi-Hua Zhou
- Department of Experimental Medicine and Jiangsu Key Laboratory for Molecular Medicine, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, China.,Department of Infectious Diseases, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, China
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