|
1
|
Wang B, Wang X, Xiao L, Xian J. Misuse of the Lower Limit of Detection in HBV DNA Testing and Anti-HBe Positive Status Will Significantly Impact the Diagnosis of Occult HBV Infection. J Viral Hepat 2025; 32:e14046. [PMID: 39673691 DOI: 10.1111/jvh.14046] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/02/2024] [Revised: 11/11/2024] [Accepted: 11/30/2024] [Indexed: 12/16/2024]
Abstract
The diagnosis of occult hepatitis B virus (HBV) infection (OBI) is influenced by factors such as the lower limit of detection (LOD) of the HBV DNA test. However, in clinical practice and scientific research, the lower limit of quantification (LOQ) is often misused as the LOD. This study aims to investigate the impact of misuse of the LOD of the HBV DNA test on the detection rate of OBI, as well as the risk factors for OBI. Four hundred twelve patients who were HBsAg-negative and had undergone high-sensitivity HBV DNA testing were included in this study. HBV DNA was detected using the Cobas 6800 System with an LOD of 2.4 IU/mL and an LOQ of 10 IU/mL. The effect of using the LOQ as the LOD on the detection rate of OBI was compared, and univariate and multivariate logistic regression analyses were used to explore the risk factors for OBI. (1) Of the 412 patients, 63.3% (n = 261) were male, with a median age of 47 (range 34-55) years. A total of 473 HBV DNA test results were obtained, with 366 individuals undergoing only one HBV DNA test and the remaining 46 patients undergoing 2 to 5 HBV DNA tests (resulting in a total of 107 test results). (2) Considering only the first HBV DNA test result, the detection rate of OBI was 4.1% (17/412). However, when the LOQ (10 IU/mL) was used as the LOD, the detection rate of OBI was only 1.5% (6/412) (p < 0.001). (3) Univariate analysis showed that there were statistically significant differences in age, anti-HBe positivity rate and anti-HBc positivity rate between OBI and non-OBI individuals (p < 0.05). Multivariate regression analysis showed that anti-HBe positivity was an independent risk factor for OBI in this study (odds ratio [OR] = 3.807, 95% confidence interval [CI]: 1.065-13.617, p = 0.040), while anti-HBs positivity was a protective factor against OBI (OR = 0.271, 95% CI: 0.093-0.787, p = 0.016). (4) Among the 46 patients who underwent repeated testing, a total of seven individuals were found to be HBV DNA-positive in the first test, and six individuals tested positive for HBV DNA one or more times in subsequent tests. When OBI was confirmed by ≥ 1 out of 1-5 tests with detectable HBV DNA, the detection rate of OBI in this study could increase from 4.1% to 5.6%. The detection rate of OBI among HBsAg-negative adult patients attending hepatology departments in this region is 4.1%. Misusing the LOQ as LOD can significantly decrease the detection rate of OBI. The presence of anti-HBe positivity and undergoing multiple HBV DNA tests can lead to a significant increase in the detection rate of OBI.
Collapse
Affiliation(s)
- Bo Wang
- Department of Hepatology, Nanjing Medical University Affiliated Taizhou People's Hospital (Jiangsu Taizhou People's Hospital), Taizhou, Jiangsu, China
| | - Xinru Wang
- Department of Hepatology, Nanjing Medical University Affiliated Taizhou People's Hospital (Jiangsu Taizhou People's Hospital), Taizhou, Jiangsu, China
| | - Li Xiao
- Department of Hepatology, Nanjing Medical University Affiliated Taizhou People's Hospital (Jiangsu Taizhou People's Hospital), Taizhou, Jiangsu, China
| | - Jianchun Xian
- Department of Hepatology, Nanjing Medical University Affiliated Taizhou People's Hospital (Jiangsu Taizhou People's Hospital), Taizhou, Jiangsu, China
| |
Collapse
|
|
2
|
Tang J, Zhao H, Zhou YH. Screening for viral hepatitis carriage. Best Pract Res Clin Obstet Gynaecol 2024; 96:102523. [PMID: 38908915 DOI: 10.1016/j.bpobgyn.2024.102523] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2023] [Revised: 05/15/2024] [Accepted: 06/12/2024] [Indexed: 06/24/2024]
Abstract
Viral hepatitis during pregnancy is common globally. In this review, we focus on the antenatal screen for hepatitis A, B, C and E, the prevention of mother-to-child transmission (MTCT) of hepatitis B and C, and the management of hepatitis A, B, C and E during pregnancy. Neonatal timely administration of hepatitis B immunoglobulin and hepatitis B vaccine is the cornerstone for preventing MTCT of hepatitis B virus (HBV), and perinatal antiviral prophylaxis with tenofovir disoproxil fumarate in mothers with positive HBeAg or HBV DNA >2 × 105 IU/ml also plays important roles in further reducing MTCT. Avoidance of risk practices in managing labor and delivery process of women with HCV infection may be useful to reduce MTCT of HCV. Early recognition of severe hepatic injury or liver failure associated with hepatitis viruses by regular liver function tests is critical to prevent maternal mortality associated with hepatitis.
Collapse
Affiliation(s)
- Jie Tang
- Department of Obstetrics and Gynecology, Wujin Hospital Affiliated with Jiangsu University, Jiangsu, China; Department of Obstetrics and Gynecology, The Wujin Clinical College of Xuzhou Medical University, Jiangsu, China
| | - Hong Zhao
- Department of Infectious Diseases, Nanjing Second Hospital, School of Medicine, Southeast University, Nanjing, China
| | - Yi-Hua Zhou
- Departments of Laboratory Medicine and Infectious Diseases and Obstetrics & Gynecology, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, China.
| |
Collapse
|
|
3
|
Al-Busafi SA, Alwassief A. Global Perspectives on the Hepatitis B Vaccination: Challenges, Achievements, and the Road to Elimination by 2030. Vaccines (Basel) 2024; 12:288. [PMID: 38543922 PMCID: PMC10975970 DOI: 10.3390/vaccines12030288] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2024] [Revised: 02/23/2024] [Accepted: 02/27/2024] [Indexed: 10/21/2024] Open
Abstract
Annually, more than 1.5 million preventable new hepatitis B (HBV) infections continue to occur, with an estimated global burden of 296 million individuals living with chronic hepatitis B infection. This substantial health challenge results in over 820,000 annual deaths being attributed to complications such as liver cirrhosis and hepatocellular carcinoma (HCC). The HBV vaccination remains the cornerstone of public health policy to prevent chronic hepatitis B and its related complications. It serves as a crucial element in the global effort to eliminate HBV, as established by the World Health Organization (WHO), with an ambitious 90% vaccination target by 2030. However, reports on global birth dose coverage reveal substantial variability, with an overall coverage rate of only 46%. This comprehensive review thoroughly examines global trends in HBV vaccination coverage, investigating the profound impact of vaccination on HBV prevalence and its consequences across diverse populations, including both high-risk and general demographics. Additionally, the review addresses the essential formidable challenges and facilitating factors for achieving WHO's HBV vaccination coverage objectives and elimination strategies in the coming decade and beyond.
Collapse
Affiliation(s)
- Said A. Al-Busafi
- Division of Gastroenterology and Hepatology, Department of Medicine, College of Medicine and Health Sciences, Sultan Qaboos University, Muscat 123, Oman
| | - Ahmed Alwassief
- Division of Gastroenterology and Hepatology, Department of Medicine, Sultan Qaboos University Hospital, Muscat 123, Oman
| |
Collapse
|
|
4
|
Mak LY, Koffas A, Dolman GE, Saleh H, Kemos P, Riddell A, Gill U, Kennedy PTF. Role of HBsAg levels in guiding hepatitis B virus prophylaxis in pregnancy: Insights from a multi-ethnic cohort. J Viral Hepat 2024; 31:3-11. [PMID: 37881873 DOI: 10.1111/jvh.13893] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/01/2023] [Revised: 09/18/2023] [Accepted: 10/06/2023] [Indexed: 10/27/2023]
Abstract
Pregnant mothers with chronic hepatitis B infection (CHB) need peri-partum antiviral prophylaxis (PAP) to reduce the risk of mother-to-child-transmission. Currently, PAP is recommended in those with high viral load (VL) that is, HBV DNA >200,000 IU/mL. Quantitative hepatitis B surface antigen (qHBsAg) >10,000 IU/mL, a cut-off derived primarily from hepatitis B e-antigen (HBeAg) positive antenatal cohorts in Chinese populations, is advocated as a surrogate marker of VL for guiding PAP. We investigated the utility of qHBsAg to predict high-VL in a multi-ethnic urban cohort with CHB. A consecutive cohort of women with CHB was identified from Barts Health NHS Trust databases in the United Kingdom. We included women with paired HBV DNA and qHBsAg during pregnancy. Women already on antiviral at conception were excluded. A total of 769 pregnancies in 678 CHB pregnant mothers (median age 31 years-old, 8.6% HBeAg+) were included. At median gestational age of 15.3 weeks, HBV DNA was 336 (IQR 44-2998) IU/mL, with 65 (8.5%) being high-VL. Serum qHBsAg was most useful in Black/Black-British/Caribbean/African (AUROC 0.946) with 100% sensitivity and 80.6% specificity to predict high-VL; but it performed less well for other ethnicities: Asian (AUROC 0.877), White (AUROC 0.797) and mixed ethnicities (AUROC 0.742). In conclusion, for settings where healthcare resources are not limited, HBV DNA remains the optimal marker to identify highly viraemic pregnancies for guiding PAP. For resource-limited settings where the prevailing cost is treatment, serum qHBsAg can be used in Black/Black British/Caribbean/African sub-cohorts, but not for other ethnicities.
Collapse
Affiliation(s)
- Lung-Yi Mak
- Barts Liver Centre, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK
- Department of Medicine, Queen Mary Hospital, School of Clinical Medicine, The University of Hong Kong, Pok Fu Lam, Hong Kong
| | - Apostolos Koffas
- Barts Liver Centre, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK
| | - Grace E Dolman
- Barts Liver Centre, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK
| | - Hossam Saleh
- Barts Liver Centre, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK
| | - Polychronis Kemos
- Barts Liver Centre, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK
| | - Anna Riddell
- Virology Department, Division of Infection, Barts Health NHS Trust, London, UK
| | - Upkar Gill
- Barts Liver Centre, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK
| | - Patrick T F Kennedy
- Barts Liver Centre, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK
| |
Collapse
|
|
5
|
Liang Q, Li N, Song S, Wei Q, Ma C, Li K, Wang S, Feng S, Wang Y. Impact of timing on protection of combined immunoprophylaxis in preventing mother-to-child transmission of hepatitis B virus: a retrospective study. J Matern Fetal Neonatal Med 2023; 36:2257837. [PMID: 37699774 DOI: 10.1080/14767058.2023.2257837] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2023] [Revised: 08/16/2023] [Accepted: 09/06/2023] [Indexed: 09/14/2023]
Abstract
Objective: To evaluate the impact of timing combined immunoprophylaxis on mother-to-child transmission (MTCT) of the hepatitis B virus (HBV) in pregnant women living with hepatitis B. Methods: A retrospective cohort study was included HBsAg-positive pregnant women who delivered full-term at Tianjin Third Central Hospital from January 2019 to December 2021. The objective of this study is to determine whether early administration of hepatitis B immune globulin (HBIG) and the first dose of hepatitis B vaccination after birth can further improve protection. Result: A total of 694 pregnant women living with hepatitis B were included; 93 infants from these mothers were lost to follow-up [including moving (n = 21), emigrating (n = 26), changing contact information (n = 27), and other reasons (n = 19)], leaving 601 infants for analysis. The incidence in babies born to mothers with hepatitis B was 1.50% (9/601). Based on the different timing of combined immunoprophylaxis administration after birth, 601 infants were divided into two groups (within 2 h and within 2-12 h). The incidence in babies born to mothers with hepatitis B were 0.32% (1/308) and 2.73% (8/293) for infants who received combined immunoprophylaxis within 2 h and between 2 and 12 h of birth, respectively (p = 0.037). The infection incidence of infants born to HBeAg-positive mothers and HBeAg-positive mothers who did not receive antiviral treatment during pregnancy was lower in the 2-h group compared to the 2-12 h group (0.72% vs. 5.84%, p = 0.04 and 1.20% vs. 9.46%, p = 0.047). Conclusion: Using combined immunoprophylaxis as soon as possible (within two hours of birth) may protect against MTCT of HBV more.
Collapse
Affiliation(s)
- Qian Liang
- The Third Central Clinical College of Tianjin Medical University, Tianjin, China
- Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Tianjin, China
- Artificial Cell Engineering Technology Research Center, Tianjin, China
- Tianjin Institute of Hepatobiliary Disease, Tianjin, China
- The Third Central Hospital of Tianjin, Tianjin, China
| | - Nan Li
- Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Tianjin, China
- Artificial Cell Engineering Technology Research Center, Tianjin, China
- Tianjin Institute of Hepatobiliary Disease, Tianjin, China
- The Third Central Hospital of Tianjin, Tianjin, China
| | - Shurong Song
- Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Tianjin, China
- Artificial Cell Engineering Technology Research Center, Tianjin, China
- Tianjin Institute of Hepatobiliary Disease, Tianjin, China
- The Third Central Hospital of Tianjin, Tianjin, China
| | - Qing Wei
- Tianjin Institute of Hepatobiliary Disease, Tianjin, China
- The Third Central Hospital of Tianjin, Tianjin, China
| | - Chunlei Ma
- Tianjin Institute of Hepatobiliary Disease, Tianjin, China
- The Third Central Hospital of Tianjin, Tianjin, China
| | - Ke Li
- Tianjin Institute of Hepatobiliary Disease, Tianjin, China
- The Third Central Hospital of Tianjin, Tianjin, China
| | - Shaohua Wang
- Tianjin Institute of Hepatobiliary Disease, Tianjin, China
- The Third Central Hospital of Tianjin, Tianjin, China
| | - Shuo Feng
- Tianjin Institute of Hepatobiliary Disease, Tianjin, China
- The Third Central Hospital of Tianjin, Tianjin, China
| | - Yingmei Wang
- Tianjin Medical University General Hospital, Tianjin, China
| |
Collapse
|
|
6
|
Liu M, Song Y, Li Y, Yang X, Zhuang H, Li J, Wang J. C2729T mutation associated with HBV mother-to-child transmission reduces HBV production via suppressing LHBs expression. Virulence 2023; 14:2189676. [PMID: 36919573 PMCID: PMC10026911 DOI: 10.1080/21505594.2023.2189676] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/16/2023] Open
Abstract
Mother-to-child transmission (MTCT) is still the main route of hepatitis B virus (HBV) infection. However, the virological factors affecting HBV MTCT have not been fully elucidated. In this study, based on a prospective cohort of mother-infant pairs with positive maternal hepatitis B surface antigen (HBsAg), we found that the average nucleotide mutation rate of HBV preS1 promoter (SPI) region in the immunoprophylaxis success group was significantly higher than that in the immunoprophylaxis failure group. Among the nucleotide mutations of the HBV SPI region, the C2729T mutation had the highest frequency. Next, we found that the C2729T mutation promoted HBsAg release but reduced HBV production by suppressing the expression of large hepatitis B surface antigen (LHBs), and overexpressing LHBs could rescue this phenomenon. Based on the fact that the C2729T mutation could alter the binding site of hepatocyte nuclear factor 1 (HNF1) in the HBV SPI region, we uncovered that such an alteration could downregulate the transcriptional activity of SPI by attenuating the binding ability of HNF1 and HBV SPI region. This study suggests that HBV C2729T mutation may contribute to the immunoprophylaxis success of HBV MTCT by reducing HBV production, which supplements the virological factors affecting HBV MTCT.
Collapse
Affiliation(s)
- Minmin Liu
- Department of Microbiology & Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China
| | - Yarong Song
- Department of Microbiology & Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China
- NHC Key Laboratory of Medical Immunology, Peking University, Beijing, China
| | - Yi Li
- Department of Microbiology & Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China
| | - Xingwen Yang
- Department of Microbiology & Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China
- NHC Key Laboratory of Medical Immunology, Peking University, Beijing, China
| | - Hui Zhuang
- Department of Microbiology & Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China
| | - Jie Li
- Department of Microbiology & Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China
| | - Jie Wang
- Department of Microbiology & Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China
- NHC Key Laboratory of Medical Immunology, Peking University, Beijing, China
| |
Collapse
|
|
7
|
Khanna D, Kar P. Can the diagnostics of hepatitis in pregnant patients be improved? Expert Rev Mol Diagn 2022; 22:1053-1055. [PMID: 36462167 DOI: 10.1080/14737159.2022.2153039] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/05/2022]
|
|
8
|
Kiweewa FM, Tierney C, Butler K, Peters MG, Vhembo T, Moodley D, Govender V, Mohtashemi N, Ship H, Musoke P, Dula D, George K, Chakhtoura N, Fowler MG, Currier JS, Bhattacharya D. Brief Report: Impact of Antiretroviral Regimen on Pregnancy and Infant Outcomes in Women With HIV/ HBV Coinfection. J Acquir Immune Defic Syndr 2022; 91:79-84. [PMID: 35621877 PMCID: PMC9377493 DOI: 10.1097/qai.0000000000003022] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2021] [Accepted: 04/28/2022] [Indexed: 11/26/2022]
Abstract
BACKGROUND There are limited data on the impact of antenatal antiretroviral regimens (ARV) on pregnancy and infant outcomes in HIV/HBV coinfection. We compared outcomes among 3 antenatal antiretroviral regimens for pregnant women with HIV/HBV. METHODS The PROMISE study enrolled ARV-naive pregnant women with HIV. Women with HBV were randomized to (no anti-HBV)-zidovudine (ZDV) + intrapartum nevirapine and 1 week of tenofovir disoproxil fumarate and emtricitabine (TDF-FTC); (3TC)-3TC + ZDV + LPV/r; or (FTC-TDF)-FTC + TDF + LPV/r. Pairwise group comparisons were performed with Fisher exact, t , or log rank tests. Adverse pregnancy outcome (APO) was a composite of low birth weight, preterm delivery, spontaneous abortion, stillbirth, or congenital anomaly. RESULTS Of 138 women with HIV/HBV, 42, 48, and 48 were analyzed in the no anti-HBV, 3TC, and FTC-TDF arms. Median age was 27 years. APOs trended lower in the no anti-HBV (26%) vs 3TC (38%), and FTC-TDF arms (35%), P ≥ 0.25). More infant deaths occurred among the FTC-TDF [6 (13%)] vs no anti-HBV [2 (5%)] and 3TC [3 (7%)] arms. There were no differences in time-to-death, HIV-free survival, birth or one-year WHO Z-score length-for-age, and head circumference. Hepatitis B e antigen (HBeAg) was associated with an increased risk of APO, 48% vs 27% (odds ratio 2.79, 95% confidence interval: 1.19 to 6.67, post hoc ). CONCLUSION With HBV/HIV coinfection, the risk of an APO was increased with maternal ARV compared with ZDV alone, although the differences were not statistically significant. Maternal HBeAg was associated with a significantly increased risk of APO. Infant mortality was highest with FTC + TDF + LPV/r. Early assessment of HBeAg could assist in identifying high-risk pregnancies for close monitoring.
Collapse
Affiliation(s)
- Flavia Matovu Kiweewa
- Makerere University—Johns Hopkins University Research Collaboration, Kampala, Uganda
- Department of Epidemiology and Biostatistics, Makerere University School of Public Health, College of Health Sciences, Kampala, Uganda
| | - Camlin Tierney
- Center for Biostatistics in AIDS Research, Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA
| | - Kevin Butler
- Center for Biostatistics in AIDS Research, Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA
| | - Marion G. Peters
- Department of Medicine, Feinberg School of Medicine, Northwestern University CRS, Chicago, IL
| | - Tichaona Vhembo
- Department of Obstetrics and Gynaecology, University of Zimbabwe College of Health Sciences, Harare, Zimbabwe
| | - Dhayendre Moodley
- Department of Obstetrics and Gynaecology, University of KwaZulu-Natal, Nelson Mandela School of Medicine, Durban, South Africa
| | - Vani Govender
- Centre for the AIDS Programme of Research in South Africa, Congella, South Africa
| | - Neaka Mohtashemi
- Department of Medicine, Division of Infectious Diseases, David Geffen School of Medicine, University of California, Los Angeles, CA
| | - Hannah Ship
- University of Miami Miller School of Medicine, Miami, FL
| | - Philippa Musoke
- Makerere University—Johns Hopkins University Research Collaboration, Kampala, Uganda
- Department of Paediatrics and Child Health, College of Health Sciences, Makerere University
| | - Dingase Dula
- Centre for AIDS Research in South Africa and Department of Obstetrics and Gynecology, School of Clinical Medicine, University of KwaZulu Natal, Durban, South Africa
| | | | - Nahida Chakhtoura
- National Institutes of Health (NIH), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), Bethesda, MD; and
| | - Mary G. Fowler
- Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD
| | - Judith S. Currier
- Department of Medicine, Division of Infectious Diseases, David Geffen School of Medicine, University of California, Los Angeles, CA
| | - Debika Bhattacharya
- Department of Medicine, Division of Infectious Diseases, David Geffen School of Medicine, University of California, Los Angeles, CA
| |
Collapse
|
|
9
|
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.
Collapse
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
| |
Collapse
|
|
10
|
Pan CQ. The role of tenofovir disoproxil fumarate for preventing vertical transmission of hepatitis B. Antivir Ther 2022; 27:13596535221076640. [DOI: 10.1177/13596535221076640] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
Background Since immunoprophylaxis failure can occur if maternal serum hepatitis B virus (HBV) DNA levels are >200,000 IU/ml, tenofovir disoproxil fumarate (TDF) therapy has been investigated for preventing mother to child transmission (PMTCT). Methods A literature search for maternal TDF therapy for PMTCT between 1/1/2015 and 7/1/21 on PUBMED, EMBASE, Cochrane, CNKI, and Wanfang databases was performed. Data from RCTs in English or Chinese were extracted and reviewed. The outcomes of interest included the efficacy and safety of TDF versus placebo for PMTCT. Results Among 11 RCTs identified from the databases, the risk-of-bias was low. All studies demonstrated that maternal TDF therapy initiated from the second or third trimester for highly viremic chronic hepatitis B mothers is highly effective and safe in the PMTCT of HBV, except one RCT performed in Thailand which showed no therapeutic advantage on TDF treatment versus placebo for PMTCT (0% vs 3% transmission). Recent emerging data suggest that maternal TDF therapy initiated at the 2nd or early 3rd trimester in mothers with HBV DNA >200,000 IU/ml achieved viremic control before delivery. In the 4-year long follow-up study for maternal TDF therapy, there were no impacts on infants’ physical growth, psychological or mental development, and bone mineral density after fetal exposure to TDF. In the light of updated efficacy and safety data from RCTs, an algorithm was proposed. The approaches in resource-limit areas were discussed. Conclusions TDF is safe for both mothers and infants as the preferred therapy for PMTCT in highly viremic mothers. TDF should be initiated at the second or early third trimester in the combination of the appropriate infants’ immunoprophylaxis.
Collapse
Affiliation(s)
- Calvin Q Pan
- Beijing Ditan Hospital, Capital Medical University, Beijing, China
- NYU Langone Health, NYU Grossman School of Medicine, New York, NY, USA
| |
Collapse
|
|
11
|
Kumar M, Abbas Z, Azami M, Belopolskaya M, Dokmeci AK, Ghazinyan H, Jia J, Jindal A, Lee HC, Lei W, Lim SG, Liu CJ, Li Q, Al Mahtab M, Muljono DH, Niriella MA, Omata M, Payawal DA, Sarin SK, Ségéral O, Tanwandee T, Trehanpati N, Visvanathan K, Yang JM, Yuen MF, Zheng Y, Zhou YH. Asian Pacific association for the study of liver (APASL) guidelines: hepatitis B virus in pregnancy. Hepatol Int 2022; 16:211-253. [PMID: 35113359 DOI: 10.1007/s12072-021-10285-5] [Citation(s) in RCA: 37] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/11/2021] [Accepted: 12/06/2021] [Indexed: 12/11/2022]
Abstract
Hepatitis B virus (HBV) infection still remains a major public health issue in the Asia-Pacific region. Most of the burden of HBV-related disease results from infections acquired in infancy through perinatal or early childhood exposure to HBV in Asia-Pacific. Hepatitis B during pregnancy presents unique management issues for both the mother and fetus. These APASL guidelines provide a comprehensive review and recommendations based on available evidence in the literature, for the management of females with HBV infection through every stage of pregnancy and postpartum. These also address the concerns, management challenges, and required follow-up of children born to hepatitis B-positive mothers.
Collapse
Affiliation(s)
- Manoj Kumar
- Department of Hepatology and Liver Transplantation, Institute of Liver and Biliary Sciences, D1 Vasant Kunj, New Delhi, 110070, India.
| | - Zaigham Abbas
- Department of Medicine, Ziauddin University Hospital, Karachi, Pakistan
| | - Milad Azami
- Faculty of Medicine, Ilam University of Medical Sciences, Ilam, Iran
| | | | - A K Dokmeci
- Department of Gastroenterology, Ankara University School of Medicine, Ankara, Turkey
| | - Hasmik Ghazinyan
- Department of Hepatology, Nork Clinical Hospital of Infectious Disease, Yerevan, Armenia
| | - Jidong Jia
- Liver Research Center, Beijing Friendship Hospital, Capital Medial University, Beijing, China
| | - Ankur Jindal
- Department of Hepatology and Liver Transplantation, Institute of Liver and Biliary Sciences, D1 Vasant Kunj, New Delhi, 110070, India
| | - Han Chu Lee
- Department of Gastroenterology, Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Wei Lei
- Hepatopancreatobiliary Center, School of Clinical Medicine, Beijing Tsinghua Changgung Hospital, Tsinghua University, Beijing, China
| | - Seng Gee Lim
- Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Chun-Jen Liu
- Department of Internal Medicine and Hepatitis Research Center, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei City, Taiwan
| | - Qiang Li
- Division of Liver Diseases Jinan Infectious Disease Hospital, Shandong University, Jinan, China
| | - Mamun Al Mahtab
- Department of Hepatology, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh
| | | | - Madunil Anuk Niriella
- Department of Medicine, Faculty of Medicine, University of Kelaniya, Ragama, Colombo, Sri Lanka
| | - Masao Omata
- Department of Gastroenterology, Yamanashi Central Hospital, Yamanashi, Japan
- University of Tokyo, Tokyo, Japan
| | - Diana A Payawal
- Fatima University Medical Center Manila, Manila, Philippines
| | - Shiv K Sarin
- Department of Hepatology and Liver Transplantation, Institute of Liver and Biliary Sciences, D1 Vasant Kunj, New Delhi, 110070, India.
| | - Olivier Ségéral
- French Agency for Research on AIDS and Viral Hepatitis, University of Health Science, Phnom Penh, Cambodia
| | - Tawesak Tanwandee
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Nirupma Trehanpati
- Department of Molecular and Cellular Medicine, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Kumar Visvanathan
- Department of Medicine, University of Melbourne, Melbourne, VIC, Australia
| | - Jin Mo Yang
- Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, South Korea
| | - Man-Fung Yuen
- Li Shu Fan Medical Foundation Professor in Medicine, The University of Hong Kong, Pok Fu Lam, Hong Kong
| | - Yingjie Zheng
- Department of Epidemiology, School of Public Health, Fudan University, Shanghai, China
| | - Y H Zhou
- Department of Laboratory Medicine, Department of Infectious Diseases, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, China
| |
Collapse
|
|
12
|
Zhu B, Lv X, Zhao Z, Chen L, Chen X, Li C, Li S, Dai E. Comparison of the efficacy and safety of tenofovir and telbivudine in interrupting mother-to-child transmission of hepatitis B virus. Medicine (Baltimore) 2021; 100:e27695. [PMID: 34871254 PMCID: PMC8568400 DOI: 10.1097/md.0000000000027695] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/29/2020] [Accepted: 10/19/2021] [Indexed: 01/05/2023] Open
Abstract
The present study is aimed to evaluate and compare the efficacy and safety of tenofovir (TDF) and telbivudine (TBV) in interrupting hepatitis B virus (HBV) mother-to-child transmission (MTCT), and to provide evidence-based treatment options to clinicians and patients.Hepatitis B e-antigen (HBeAg)-positive pregnant women (644 in total) with high HBV DNA load (≥2 × 105 IU/mL) and who received TDF (n = 214) or TBV (n = 380) in the second or third trimester, or received no treatment (n = 50) were included in this retrospective analysis.HBV DNA levels in mothers at delivery were significantly lower than baseline in the 2 treatment groups. HBV DNA levels in the TDF group were significantly different between the mothers receiving treatment in the second trimester and those receiving treatment in the third trimester; however, significant difference was not observed in the TBV group. The proportion of hepatitis B surface antigen (HBsAg)-positive infants at the age of 7 to 12 months in the TDF, TBV, and control groups were 0.00% (0/174), 0.30% (1/331), and 5.0% (2/40) with a significant difference between the treatment groups and the control group, but no difference between the TDF and TBV group (P > .05). However, no serious adverse events were observed in infants and mothers of all groups.TBV and TDF can effectively reduce the HBV DNA level and MTCT rate in pregnant women with high HBV DNA load (≥2 × 105 IU/mL); both antiviral drugs are safe for infants and mothers. Since TDF was more effective in reducing HBV DNA levels during the second trimester, its use during the period is recommended to prevent HBV MTCT.
Collapse
Affiliation(s)
- Bo Zhu
- Department of Epidemiology and Statistics, North China University of Science and Technology, Tangshan, China
| | - Xiaojing Lv
- Preventive Health Branch, Shijiazhuang Maternal and Child Health Hospital, Shijiazhuang, China
| | - Zhiying Zhao
- Preventive Health Branch, Shijiazhuang Maternal and Child Health Hospital, Shijiazhuang, China
| | - Liwen Chen
- Preventive Health Branch, Shijiazhuang Maternal and Child Health Hospital, Shijiazhuang, China
| | - Xiuli Chen
- Department of Laboratory Medicine, The Fifth Hospital of Shijiazhuang, North China University of Science and Technology, Shijiazhuang, China
| | - Congjie Li
- Preventive Health Branch, Shijiazhuang Maternal and Child Health Hospital, Shijiazhuang, China
| | - Suwen Li
- Department of Laboratory Medicine, The Fifth Hospital of Shijiazhuang, North China University of Science and Technology, Shijiazhuang, China
| | - Erhei Dai
- Department of Laboratory Medicine, The Fifth Hospital of Shijiazhuang, North China University of Science and Technology, Shijiazhuang, China
| |
Collapse
|
|
13
|
Wang C, Pan YC, Jia ZF, Chi XM, Wang YQ, Yang N, Wu YH, Niu JQ, Jiang J. The relationship between hepatitis B virus serum DNA, RNA and quantitative hepatitis B surface antigen, and the predictive value for mother-to-child transmission: an observational cohort study. BJOG 2021; 129:241-247. [PMID: 34455680 DOI: 10.1111/1471-0528.16884] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/20/2021] [Indexed: 01/01/2023]
Abstract
OBJECTIVE To explore the relationships between hepatitis B virus (HBV) DNA, HBV RNA and hepatitis B surface antigen (HBsAg) and to evaluate their predictive value for mother-to-child transmission of HBV. DESIGN An observational cohort study. SETTING First Hospital of Jilin University. POPULATION HBsAg-positive and hepatitis B e antigen (HBeAg) -positive pregnant women were recruited. METHODS Blood samples were collected from mothers before delivery, and HBV infection of infants was evaluated at 7 months of age. RESULTS Overall, 268 mothers and 271 infants were enrolled. HBV DNA and HBsAg levels were correlated (rs = 0.699; P < 0.001), and HBV DNA (rs = 0.500; P < 0.001) and HBsAg (rs = 0.372; P < 0.001) were both correlated with HBV RNA. The areas under the curve for HBV DNA, HBsAg and HBV RNA for prediction of infection were 0.69 (95% CI 0.57-0.82), 0.63 (95% CI 0.51-0.76) and 0.65 (95% CI 0.52-0.78), respectively. Higher HBV DNA (odds ratio [OR] 4.77, 95% CI 1.44-15.86), higher HBsAg (OR 4.13, 95% CI 1.12-15.25) and higher HBV RNA (OR 3.19, 95% CI 1.09-9.32) were risk factors for HBV infection. Analysis of the HBV DNA-RNA-HBsAg Score revealed that it was an independent predictive factor for mother-to-child transmission (the OR of Score 3 was 8.81, 95% CI 2.79-27.82). CONCLUSION HBV DNA, HBV RNA and HBsAg were correlated in HBeAg-positive pregnant women. HBsAg could be considered as a substitute marker of HBV DNA for HBeAg-positive pregnant women in low-income regions. We should pay special attention to pregnant women with high levels of all three markers. TWEETABLE ABSTRACT HBsAg could be considered as a substitute marker of HBV DNA for HBeAg-positive pregnant women in low-income regions. Special attention should be given to pregnant women with high levels of all three markers (HBV DNA, HBV RNA and HBsAg).
Collapse
Affiliation(s)
- C Wang
- Department of Hepatology, First Hospital of Jilin University, Changchun, China
| | - Y-C Pan
- Division of Clinical Research, First Hospital of Jilin University, Changchun, China
| | - Z-F Jia
- Division of Clinical Research, First Hospital of Jilin University, Changchun, China
| | - X-M Chi
- Department of Hepatology, First Hospital of Jilin University, Changchun, China
| | - Y-Q Wang
- Division of Clinical Research, First Hospital of Jilin University, Changchun, China
| | - N Yang
- Division of Clinical Research, First Hospital of Jilin University, Changchun, China
| | - Y-H Wu
- Division of Clinical Research, First Hospital of Jilin University, Changchun, China
| | - J-Q Niu
- Department of Hepatology, First Hospital of Jilin University, Changchun, China
| | - J Jiang
- Division of Clinical Research, First Hospital of Jilin University, Changchun, China
| |
Collapse
|
|
14
|
Belopolskaya M, Avrutin V, Kalinina O, Dmitriev A, Gusev D. Chronic hepatitis B in pregnant women: Current trends and approaches. World J Gastroenterol 2021; 27:3279-3289. [PMID: 34163111 PMCID: PMC8218362 DOI: 10.3748/wjg.v27.i23.3279] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/28/2021] [Revised: 03/10/2021] [Accepted: 04/22/2021] [Indexed: 02/06/2023] Open
Abstract
Chronic hepatitis B (CHB) is a significant public health problem worldwide. The aim of the present review is to summarize the actual trends in the management of CHB in pregnant women. The prevalence of hepatitis B virus (HBV) infection in pregnant women is usually comparable to that in the general population in the corresponding geographic area. All women have to be screened for hepatitis B surface antigen (HBsAg) during pregnancy. Additional examinations of pregnant women with CHB may include maternal hepatitis B e antigen, HBV viral load, alanine aminotransferase level, and HBsAg level. The management of pregnancy depends on the phase of the HBV infection, which has to be determined before pregnancy. In women of childbearing age with CHB, antiviral therapy can pursue two main goals: Treatment of active CHB, and vertical transmission prevention. During pregnancy, tenofovir is the drug of choice in both cases. A combination of hepatitis B immunoglobulin and vaccine against hepatitis B should be administered within the first 12 h to all infants born to mothers with CHB. In such cases, there are no contraindications to breastfeeding.
Collapse
Affiliation(s)
- Maria Belopolskaya
- Polyclinical Department, Botkin's Infectious Disease Hospital, St-Petersburg 195067, Russia
- Chronic Viral Infectious Disease Lab, Institute of Experimental Medicine, St-Petersburg 197376, Russia
| | - Viktor Avrutin
- Institute for Systems Theory, University of Stuttgart, Stuttgart 70569, Baden-Wurttemberg, Germany
| | - Olga Kalinina
- Faculty of Biomedical Sciences, Almazov National Medical Research Centre, St-Petersburg 197341, Russia
| | - Alexander Dmitriev
- Department of Molecular Microbiology, Institute of Experimental Medicine, St-Petersburg 197376, Russia
| | - Denis Gusev
- Botkin's Infectious Disease Hospital, St-Petersburg 195067, Russia
| |
Collapse
|
|
15
|
Li AY, Liu Z, Song Y, Xiao Y, Jiang J, Li L, Zhai X, Liu J, Duan Z, Ding F, Liu J, Zhuang H, Zhu L, Jiang J, Zou H, Wang J, Li J. Reduction of the occurrence of occult HBV infection in infants by increasing the dose of hepatitis B vaccine: a large prospective cohort study. Emerg Microbes Infect 2021; 9:1881-1891. [PMID: 32779526 PMCID: PMC7473118 DOI: 10.1080/22221751.2020.1808533] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Occult hepatitis B virus (HBV) infection (OBI) has been observed among infants born to hepatitis B surface antigen (HBsAg)-positive mothers despite successful immunoprophylaxis. This study enrolled 549 infants [349 infants received a 10μg/dose of hepatitis B vaccine (HepB), and 200 infants received 20μg/dose HepB] born to HBsAg-positive mothers with HBV DNA load >6log10IU/mL. The anti-HBs levels in the 10μg group were significantly lower than that in the 20μg group both at 7 [652.48 (564.05-754.82) vs. 1541.72 (1268.69-1873.51) mIU/mL, P<0.001] and 12 months old [257.44 (220.29-300.88) vs. 1073.41 (839.27-1372.78) mIU/mL, P<0.001]. The OBI incidence in the 10μg group was significantly higher than that in the 20μg group at both 7 [21.55% (25/116) vs. 7.56% (9/119), P=0.002] and 12 months old [17.07% (14/82) vs. 6.90% (6/87), P=0.041]. OBI incidence in infants with anti-HBs levels <100mIU/mL was higher than that of those with anti-HBs ≥100mIU/mL [35.71% (5/14) vs. 13.12% (29/221), P=0.036]. This study showed that increasing the immunisation dose from 10μg to 20μg significantly improved anti-HBs levels and decreased OBI incidence in infants with a high maternal viral load. We recommend 20μg HepB to treat this high-risk population.
Collapse
Affiliation(s)
- Authors Yi Li
- Department of Microbiology & Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, People's Republic of China
| | - Zhixiu Liu
- Department of Microbiology & Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, People's Republic of China
| | - Yarong Song
- Department of Microbiology & Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, People's Republic of China
| | - Yiwei Xiao
- Department of Microbiology & Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, People's Republic of China
| | - Jing Jiang
- Department of Clinical Research, First Hospital of Jilin University, Changchun, People's Republic of China
| | - Lili Li
- Department of Microbiology & Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, People's Republic of China
| | - Xiangjun Zhai
- Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, People's Republic of China
| | - Jianxun Liu
- Zhengzhou Municipal Center for Disease Control and Prevention, Zhengzhou, People's Republic of China
| | - Zhongping Duan
- Beijing Youan Hospital, Capital Medical University, Beijing, People's Republic of China
| | - Feng Ding
- Department of Microbiology & Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, People's Republic of China
| | - Jia Liu
- Department of Microbiology & Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, People's Republic of China
| | - Hui Zhuang
- Department of Microbiology & Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, People's Republic of China
| | - Liguo Zhu
- Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, People's Republic of China
| | - Jie Jiang
- Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, People's Republic of China
| | - Huaibin Zou
- Beijing Youan Hospital, Capital Medical University, Beijing, People's Republic of China
| | - Jie Wang
- Department of Microbiology & Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, People's Republic of China
| | - Jie Li
- Department of Microbiology & Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, People's Republic of China
| |
Collapse
|
|
16
|
Lu Y, Song Y, Zhai X, Zhu F, Liu J, Chang Z, Li Y, Xiao Y, Li L, Liu M, Liu J, Duan Z, Zou H, Zhuang H, Wang J, Li J. Maternal hepatitis B e antigen can be an indicator for antiviral prophylaxis of perinatal transmission of hepatitis B virus. Emerg Microbes Infect 2021; 10:555-564. [PMID: 33682609 PMCID: PMC8018376 DOI: 10.1080/22221751.2021.1899055] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/27/2022]
Abstract
As a high-risk factor of perinatal HBV transmission, the potential role of maternal hepatitis B e antigen (HBeAg) to guide antiviral prophylaxis has not yet been fully reported. This large prospective cohort study enrolled 1177 hepatitis B surface antigen (HBsAg)-positive pregnant women without antiviral treatment and their newborns. HBeAg, HBsAg, and viral load in maternal serum collected before delivery were measured. All the newborns were given standard passive-active immunoprophylaxis within 12 h after birth, and post-vaccination serologic testing was performed at 7 (±7d) months of age. The results revealed that 20 of the 1177 infants (1.70%) were immunoprophylaxis failure, and all their mothers were HBeAg positive. Maternal quantitative HBeAg was positively correlated with viral load (r = 0.83; P < .0001) and quantitative HBsAg (r = 0.68; P < .0001). The area under the receiver operating characteristic curve (AUC) for predicting immunoprophylaxis failure by maternal HBeAg was comparable to that by maternal viral load (0.871 vs 0.893; P = .441) and HBsAg (0.871 vs 0.871; P = .965). The optimal cutoff value of maternal quantitative HBeAg to predict perinatal infection was 2.21 log10 PEI U/mL, and the sensitivity and specificity was 100.0% and 74.5%, respectively. According to maternal viral load >2 × 105 IU/mL, the sensitivity and specificity of maternal qualitative HBeAg to identify the risk of HBV MTCT for pregnant women and determine the necessity for antiviral prophylaxis was 95.5% and 92.6%, respectively. This study showed that maternal HBeAg can be a surrogate marker of HBV DNA for monitoring and evaluating whether antiviral prophylaxis is necessary for preventing perinatal HBV transmission.
Collapse
Affiliation(s)
- Ying Lu
- Department of Microbiology & Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, People's Republic of China
| | - Yarong Song
- Department of Microbiology & Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, People's Republic of China
| | - Xiangjun Zhai
- Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, People's Republic of China
| | - Fengcai Zhu
- Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, People's Republic of China
| | - Jianxun Liu
- Zhengzhou Municipal Center for Disease Control and Prevention, Zhengzhou, People's Republic of China
| | - Zhanjun Chang
- Zhengzhou Municipal Center for Disease Control and Prevention, Zhengzhou, People's Republic of China
| | - Yi Li
- Department of Microbiology & Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, People's Republic of China
| | - Yiwei Xiao
- Department of Microbiology & Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, People's Republic of China
| | - Lili Li
- Department of Microbiology & Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, People's Republic of China
| | - Minmin Liu
- Department of Microbiology & Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, People's Republic of China
| | - Jia Liu
- Department of Microbiology & Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, People's Republic of China
| | - Zhongping Duan
- Beijing Youan Hospital, Capital Medical University, Beijing, People's Republic of China
| | - Huaibin Zou
- Beijing Youan Hospital, Capital Medical University, Beijing, People's Republic of China
| | - Hui Zhuang
- Department of Microbiology & Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, People's Republic of China
| | - Jie Wang
- Department of Microbiology & Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, People's Republic of China
| | - Jie Li
- Department of Microbiology & Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, People's Republic of China
| |
Collapse
|
|
17
|
Terrault NA, Levy MT, Cheung KW, Jourdain G. Viral hepatitis and pregnancy. Nat Rev Gastroenterol Hepatol 2021; 18:117-130. [PMID: 33046891 DOI: 10.1038/s41575-020-00361-w] [Citation(s) in RCA: 65] [Impact Index Per Article: 16.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 08/21/2020] [Indexed: 02/06/2023]
Abstract
The management of viral hepatitis in the setting of pregnancy requires special consideration. There are five liver-specific viruses (hepatitis A, B, C, D, E), each with unique epidemiology, tendency to chronicity, risk of liver complications and response to antiviral therapies. In the setting of pregnancy, the liver health of the mother, the influence of pregnancy on the clinical course of the viral infection and the effect of the virus or liver disease on the developing infant must be considered. Although all hepatitis viruses can harm the mother and the child, the greatest risk to maternal health and subsequently the fetus is seen with acute hepatitis A virus or hepatitis E virus infection during pregnancy. By contrast, the primary risks for hepatitis B virus (HBV), hepatitis C virus (HCV) and hepatitis D virus are related to the severity of the underlying liver disease in the mother and the risk of mother-to-child transmission (MTCT) for HBV and HCV. The prevention of MTCT is key to reducing the global burden of chronic viral hepatitis, and prevention strategies must take into consideration local health-care and socioeconomic challenges. This Review presents the epidemiology of acute and chronic viral hepatitis infection in pregnancy, the effect of pregnancy on the course of viral infection and, conversely, the influence of the viral infection on maternal and infant outcomes, including MTCT.
Collapse
Affiliation(s)
- Norah A Terrault
- Keck School of Medicine, University of Southern California, Los Angeles, USA.
| | - Miriam T Levy
- Department of Gastroenterology and Liver, Liverpool Hospital, University of New South Wales, Sydney, New South Wales, Australia
| | - Ka Wang Cheung
- Department of Obstetrics and Gynaecology, Queen Mary Hospital, University of Hong Kong, Hong Kong, Hong Kong
| | - Gonzague Jourdain
- French National Research Institute for Sustainable Development (IRD), Marseille, France.,Chiang Mai University, Chiang Mai, Thailand
| |
Collapse
|
|
18
|
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.
Collapse
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
| |
Collapse
|
|
19
|
Zhao H, Zhou X, Zhou YH. Hepatitis B vaccine development and implementation. Hum Vaccin Immunother 2020; 16:1533-1544. [PMID: 32186974 PMCID: PMC7482909 DOI: 10.1080/21645515.2020.1732166] [Citation(s) in RCA: 60] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2019] [Accepted: 02/15/2020] [Indexed: 12/12/2022] Open
Abstract
Vaccination against hepatitis B is the most effective strategy to control HBV infection. The first licensed hepatitis B vaccine was developed by the purification of hepatitis B surface antigen (HBsAg) from plasma of asymptomatic HBsAg carriers. Then, the recombinant DNA technology enabled the development of recombinant hepatitis B vaccine. A series of three doses vaccine can elicit long-term protection more than 30 y. Concurrent use of hepatitis B immunoglobulin and hepatitis B vaccine has substantially reduced the mother-to-child transmission of HBV, nearly zero infection in children of carrier mother with negative hepatitis B e antigen (HBeAg) and 5-10% infection in children of HBeAg-positive mothers. By the end of 2018, 189 countries adopted universal hepatitis B vaccination program, which has dramatically reduced the global prevalence of HBsAg in children <5 y of age, from 4.7% in the prevaccine era to 1.3% in 2015. However, the implementation of universal hepatitis B vaccination in some regions is suboptimal and timely birth dose vaccine is not routinely administered in more than half of newborn infants. Optimal worldwide universal hepatitis B vaccination requires more efforts to overcome the social and economic challenges.
Collapse
Affiliation(s)
- Hong Zhao
- Department of Infectious Diseases, The Second Hospital of Nanjing, School of Medicine, Southeast University, Nanjing, China
| | - Xiaoying Zhou
- Department of Internal Medicine, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China
| | - Yi-Hua Zhou
- Departments of Laboratory Medicine and Infectious Diseases, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, China
| |
Collapse
|
|
20
|
Chen T, Liu J, Yu Q, Yao N, Yang Y, Wu Y, Ren D, Tian Z, Zhao Y, Wang J. Tenofovir plus hepatitis B immunoglobulin treatment resulted in a rapid HBV DNA load decline in high-risk pregnant women who missed the optimal time window of antiviral prophylaxis. Antivir Ther 2020; 24:125-131. [PMID: 30570488 DOI: 10.3851/imp3284] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/12/2018] [Indexed: 10/27/2022]
Abstract
BACKGROUND Tenofovir disoproxil fumarate (TDF) administration in the third trimester for pregnant women with high HBV DNA load has been accepted as a wise practice to prevent mother-to-infant transmission (MTIT). However, for those women who missed the optimal time window of antiviral prophylaxis, this treatment is lacking in the current clinical guidelines. METHODS Forty-eight pregnant women who did not receive antiviral prophylaxis before 28 weeks of gestation were screened and were administrated with TDF plus hepatitis B immunoglobulin (HBIG; TDF+HBIG group) or TDF alone (TDF group). HBV DNA inhibition and the safety profile were compared between two groups. RESULTS A decline of HBV DNA load was observed in both groups after a short period of treatment, and no infant had MTIT. However, compared with the TDF group, the speed of HBV DNA load decline was more rapid (P=0.002) and a much more striking HBV DNA load decline in the first 4 weeks of treatment was exhibited in the TDF+HBIG group (P=0.001). The percentages of mothers with HBV DNA <4 log10 IU/ml and 3 log10 IU/ml at delivery were both much higher in the TDF+HBIG group than the TDF group (P=0.034 and 0.024, respectively). TDF and HBIG were found to be well-tolerated with no safety concerns in the mothers and their infants. CONCLUSIONS TDF plus HBIG treatment resulted in a rapid HBV DNA load decline in high-risk women who missed the optimal time window of antiviral prophylaxis in pregnancy, which potentially protected infants from HBV infection.
Collapse
Affiliation(s)
- Tianyan Chen
- Department of Infectious Diseases, First Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an City, China
| | - Jinfeng Liu
- Department of Infectious Diseases, First Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an City, China
| | - Qiang Yu
- Department of Pediatric Surgery, Second Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an City, China
| | - Naijuan Yao
- Department of Infectious Diseases, First Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an City, China
| | - Yuan Yang
- Department of Infectious Diseases, First Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an City, China
| | - Yuchao Wu
- Department of Infectious Diseases, First Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an City, China
| | - Danfeng Ren
- Department of Infectious Diseases, First Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an City, China
| | - Zhen Tian
- Department of Infectious Diseases, First Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an City, China
| | - Yingren Zhao
- Department of Infectious Diseases, First Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an City, China
| | - Jing Wang
- Department of Infectious Diseases, First Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an City, China.,Department of Rheumatology, First Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an City, China
| |
Collapse
|
|
21
|
Xiao Y, Sun K, Duan Z, Liu Z, Li Y, Yan L, Song Y, Zou H, Zhuang H, Wang J, Li J. Quasispecies characteristic in "a" determinant region is a potential predictor for the risk of immunoprophylaxis failure of mother-to-child-transmission of sub-genotype C2 hepatitis B virus: a prospective nested case-control study. Gut 2020; 69:933-941. [PMID: 31446427 PMCID: PMC7229894 DOI: 10.1136/gutjnl-2019-318278] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/14/2019] [Revised: 08/05/2019] [Accepted: 08/17/2019] [Indexed: 12/12/2022]
Abstract
OBJECTIVE This study was performed to explore the correlation between the characteristics of hepatitis B virus (HBV) quasispecies in HBV-infected pregnant women and the risk of immunoprophylaxis failure for their infants. DESIGN In this prospective nested case-control study, the characteristics of HBV quasispecies in mothers whose infants were immunoprophylaxis success (control group) and those whose infants were immunoprophylaxis failure (case group) were analysed by the clone-based sequencing of full-length HBV genome and next-generation sequencing (NGS) of "a" determinant region, and were compared between the two groups. RESULTS The quasispecies characteristics including mutant frequency, Shannon entropy and mean genetic distance at amino acid level of "a" determinant region were significantly lower in case group than that in control group, using the full-length HBV genome clone-based sequencing assay. These results were confirmed by NGS assay. Notably, we discovered that the differences were also significant at nucleotide level by NGS assay. Furthermore, the risk of immunoprophylaxis failure could be predicted by analysing the three HBV quasispecies characteristics either at nucleotide level or at amino acid level of "a" determinant region, and the corresponding predictive values were tentatively set up. CONCLUSIONS HBV quasispecies with a more complex mutant spectrum in "a" determinant region might be more vulnerable to extinct through mother-to-child-transmission (MTCT). More importantly, analysing HBV quasispecies characteristics in pregnant women with high HBV DNA load might be helpful to predict the high-risk population of immunoprophylaxis failure, and consequently provide accurate intervention against MTCT of HBV.
Collapse
Affiliation(s)
- Yiwei Xiao
- Department of Microbiology & Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, 100083, P.R. China
| | - Kuixia Sun
- Department of Microbiology & Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, 100083, P.R. China,Department of Clinical Laboratory, Peking University First Hospital, Beijing, 100034, P.R. China
| | - Zhongping Duan
- Artificial Liver Center, Beijing Youan Hospital, Capital Medical University, Beijing, 100054, P.R. China
| | - Zhixiu Liu
- Department of Microbiology & Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, 100083, P.R. China
| | - Yi Li
- Department of Microbiology & Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, 100083, P.R. China
| | - Ling Yan
- Department of Microbiology & Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, 100083, P.R. China
| | - Yarong Song
- Department of Microbiology & Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, 100083, P.R. China
| | - Huaibin Zou
- Artificial Liver Center, Beijing Youan Hospital, Capital Medical University, Beijing, 100054, P.R. China
| | - Hui Zhuang
- Department of Microbiology & Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, 100083, P.R. China
| | - Jie Wang
- Department of Microbiology & Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, 100083, P.R. China
| | - Jie Li
- Department of Microbiology & Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, 100083, P.R. China
| |
Collapse
|
|
22
|
Hepatitis B - Vertical transmission and the prevention of mother-to-child transmission. Best Pract Res Clin Obstet Gynaecol 2020; 68:78-88. [PMID: 32249130 DOI: 10.1016/j.bpobgyn.2020.02.014] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2019] [Revised: 02/21/2020] [Accepted: 02/26/2020] [Indexed: 12/20/2022]
Abstract
Hepatitis B virus (HBV) infection is the commonest cause of chronic hepatitis, with an estimated global prevalence of 3.5%, and which leads to significant morbidity and mortality. Mother-to-child transmission (MTCT) during pregnancy is the leading form of transmission in endemic populations, and its interruption is thus crucial as the initial step in the elimination of HBV infection, notwithstanding the availability of potent antiviral medications. The risk of MTCT is dramatically reduced by timely neonatal HBV vaccination and the administration of hepatitis B immunoglobulin after birth in high-risk infants. Maternal HBV DNA quantification during pregnancy allows the assessment of the risk of newborn immunoprophylaxis failure (IF). Maternal antiviral treatment in highly viremic women can reduce the risk of IF. However, the optimal HBV DNA cutoff level for the initiation of antiviral treatment remains to be determined.
Collapse
|
|
23
|
Peng S, Wan Z, Liu T, Wang Y, Chen H, Li X, Du Y. Quantitative Hepatitis B Surface Antigen Predicts Hepatitis B Transmission in Infants Born to e Antigen-positive Mothers. J Clin Gastroenterol 2020; 54:76-82. [PMID: 30575631 DOI: 10.1097/mcg.0000000000001158] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
GOALS This study aimed to explore whether quantitative surface antigen [hepatitis B surface antigen (HBsAg)] can be used as a surrogate marker of hepatitis B virus (HBV) DNA to predict hepatitis B transmission before the first hepatitis vaccine dose in infants born to hepatitis B e antigen (HBeAg)-positive pregnant women. BACKGROUND Currently, HBV transmission persistently occurs worldwide, especially in infants born to e antigen (HBeAg)-positive highly viremic mothers. However, due to high cost, the extensive use of viral load testing to identify these high-risk mothers is limited. MATERIALS AND METHODS In total of 275 HBeAg-positive pregnant women paired with 280 infants were enrolled in this study. Quantitative HBsAg and HBV DNA levels were measured in the third trimester. Spearman rank correlation was used to assess the correlation between HBsAg levels and viral load, and multivariate logistic regression to identify factors related to HBV transmission in infants. RESULTS Among 280 infants included, 15 (5.4%) infants were infected with HBV. In this study, we observed that quantitative HBsAg was positively correlated with maternal viral load (r=0.70, P<0.001) and highly predicted HBV transmission in infants born to HBeAg-positive mothers with area under the curve of 0.76 (95% confidence interval, 0.71-0.81). The optimum threshold HBsAg levels above 4.6 log10 IU/mL to predict HBV transmission in infants had a sensitivity of 80.0%, specificity of 67.9%. CONCLUSIONS Quantitative HBsAg could be used as a surrogate marker of HBV DNA levels to predict hepatitis B transmission occurring before the injection of first-dose vaccine in infants born to e antigen-positive mothers.
Collapse
Affiliation(s)
- Songxu Peng
- Department of Maternal and Child Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology.,Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Zhihua Wan
- Department of Maternal and Child Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology.,Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Tingting Liu
- Department of Maternal and Child Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology.,Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Yanni Wang
- Department of Maternal and Child Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology.,Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Hongyan Chen
- Department of Maternal and Child Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology.,Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Xiu Li
- Department of Maternal and Child Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology.,Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Yukai Du
- Department of Maternal and Child Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology.,Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| |
Collapse
|
|
24
|
Liu J, Wang J, Yan T, Du D, Qi C, Cao F, Yao N, Yang Y, He Y, Tian Z, Ren D, Zhu L, Chen T, Zhao Y. Efficacy and safety of telbivudine and tenofovir disoproxil fumarate in preventing hepatitis B vertical transmission: A real-life practice. J Viral Hepat 2019; 26:1170-1177. [PMID: 31177596 DOI: 10.1111/jvh.13156] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/11/2019] [Revised: 04/17/2019] [Accepted: 05/08/2019] [Indexed: 12/12/2022]
Abstract
Mother-to-child transmission (MTCT) is a major obstacle in the elimination of hepatitis B virus (HBV) infection. Telbivudine (LdT) and tenofovir disoproxil fumarate (TDF) are the two most common antiviral medicines for preventing MTCT. However, the efficacy and safety of LdT and TDF in preventing HBV vertical transmission during the second to third trimester have not been compared rigorously. Therefore, we carried out a prospective multicentre cohort study of chronic hepatitis B in mothers with HBV DNA > 106 IU/mL, receiving LdT or TDF during the second to third trimester. Among the 893 mothers enrolled, 857 (LdT/TDF/untreated group (NTx) = 396/325/136) completed consecutive follow-up with 854 infants (LdT/TDF/NTx = 395/323/136). LdT and TDF treatment resulted in a similar decrease of HBV DNA in mothers at delivery. Multivariate analysis indicated that only HBsAg titre at the baseline correlated with viral DNA decrease (P = 0.015). With intention-to-treat analysis, MTCT rates in the LdT, TDF and NTx group were 4.41%, 2.42% and 22.08%, respectively. An increasing vertical transmission rate was found to be closely associated with higher HBsAg titre, 5.32% and 17.65% infection rate was estimated in infants born to mothers with HBsAg > 4 and >5 log10 IU/mL, respectively. No serious side effects were reported in either mothers or infants. LdT and TDF treatments were well tolerated and showed comparable efficacy in reducing MTCT. Higher risk of MTCT was shown in pregnant women with HBsAg > 4 log10 IU/mL.
Collapse
Affiliation(s)
- Jinfeng Liu
- Department of Infectious Diseases, The First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, China
| | - Jing Wang
- Department of Rheumatology and Immunology, The First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, China
| | - Taotao Yan
- Department of Infectious Diseases, The First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, China
| | - Dan Du
- Department of Infectious Diseases, The First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, China
| | - Caijing Qi
- Department of Gynecology and Obstetrics, The First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, China
| | - Furong Cao
- Department of Neonatology, The First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, China
| | - Naijuan Yao
- Department of Infectious Diseases, The First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, China
| | - Yuan Yang
- Department of Infectious Diseases, The First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, China
| | - Yingli He
- Department of Infectious Diseases, The First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, China
| | - Zhen Tian
- Department of Infectious Diseases, The First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, China
| | - Danfeng Ren
- Department of Infectious Diseases, The First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, China
| | - Li Zhu
- Department of Infectious Diseases, The First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, China
| | - Tianyan Chen
- Department of Infectious Diseases, The First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, China
| | - Yingren Zhao
- Department of Infectious Diseases, The First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, China
| |
Collapse
|
|
25
|
Han LF, Zheng JM, Zheng LQ, Gao HB, Chen LX, Xu QL, Chai YH, Zhang X, Pan C, Yao LF. Telbivudine can safely reduce mother-to-child transmission in chronic hepatitis B women after 12 weeks of gestation. BMC Infect Dis 2019; 19:614. [PMID: 31299917 PMCID: PMC6626355 DOI: 10.1186/s12879-019-4250-6] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2018] [Accepted: 07/03/2019] [Indexed: 12/12/2022] Open
Abstract
Background To evaluate the efficacy and safety of telbivudine in chronic hepatitis B women during the second and third trimesters of pregnancy. Methods The week 12–34 of pregnant women were screened in this prospective non-intervention study, with HBV DNA > 106 IU/mL and alanine aminotransferase > 50 IU/L. The patients were received telbivudine treatment as a treatment group or without antiviral treatment as a control group. All infants were received recombinant hepatitis B vaccine 10 μg within 12 h of birth, at week 4 and week 24, immunoglobulin G within 12 h of birth and were detected HBV markers at the range from 7 to 12 months after delivery. Results A total of 241 patients were finally enrolled, 139 patients in telbivudine group and 102 patients in control group. HBsAg negative rate of infants was 99.3% (135/136) in telbivudine group and was 91.9% (91/99) in control group after 7 months (P = 0.005), respectively. The incidence of undetectable HBV DNA levels (47.5%) was significantly lower in telbivudine-treated mothers than that in the controls (0%), and 75.5% patients alanine aminotransferase returned to normal in telbivudine group, and 51% in control group at delivery (P < 0.001), respectively. Conclusions Telbivudine can safely reduce mother-to-child transmission in chronic hepatitis B women after 12 weeks of gestation.
Collapse
Affiliation(s)
- Li-Fen Han
- Department of Liver Diseases, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, 350025, China
| | - Jian-Ming Zheng
- Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, 200040, China
| | - Li-Qing Zheng
- Department of Liver Diseases, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, 350025, China
| | - Hai-Bing Gao
- Department of Liver Diseases, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, 350025, China
| | - Li-Xia Chen
- Department of Liver Diseases, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, 350025, China
| | - Qing-Ling Xu
- Department of Liver Diseases, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, 350025, China
| | - Yi-Hong Chai
- Department of Liver Diseases, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, 350025, China
| | - Xin Zhang
- Department of Liver Diseases, The Second Hospital of Longyan, Fuzhou, 350025, China
| | - Chen Pan
- Department of Liver Diseases, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, 350025, China
| | - Lv-Feng Yao
- Department of Liver Diseases, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, 350025, China.
| |
Collapse
|
|
26
|
Telbivudine Treatment during Late Pregnancy Prevents Mother-to-Child Transmission of Hepatitis B Virus: A Retrospective Study. Can J Gastroenterol Hepatol 2019; 2019:9046260. [PMID: 31380321 PMCID: PMC6652084 DOI: 10.1155/2019/9046260] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/05/2018] [Revised: 04/01/2019] [Accepted: 06/24/2019] [Indexed: 12/21/2022] Open
Abstract
PURPOSE To investigate the efficacy of telbivudine (LdT) in blocking mother-to-child transmission (MTCT) of hepatitis B virus (HBV) during late pregnancy. METHODS A total of 651 pregnant women aged 18-40 in Nantong Third People's Hospital and Hospital affiliated to Nantong University with positive hepatitis B surface antigen (HBsAg) and HBV DNA were enrolled between January 2011 and December 2015. Patients with HBV DNA≥106 copies/mL (n=251) received LdT during late pregnancy according to the patients' will, while 136 high viral patients with HBV DNA≥106 copies/mL who did not take LdT therapy and 268 low viral patients with HBV DNA<106 copies/mL served as the controls. RESULTS At 7 months and 1 year postpartum, the basal HBV DNA serum level of treated patients declined significantly (P<0.001), while no obvious decline was observed in the untreated high viraemic controls (P<0.05) and untreated low viraemic controls (P<0.05). Only 1 infant (0.4%) in LdT group was HBsAg positive at 7 months, while 14 (5.2%) were in the untreated low viraemic controls (P<0.001) and 15 (11.0%) were in untreated high viraemic controls (P<0.001). CONCLUSION For pregnant women with HBV DNA≥106 copies/mL, the use of LdT during late pregnancy could effectively reduce the MTCT rate of HBV.
Collapse
|
|
27
|
Issues Meriting Further Study in Preventing Mother-to-Infant Transmission of Hepatitis B by Antiviral Therapy During Pregnancy. MATERNAL-FETAL MEDICINE 2019. [DOI: 10.1097/fm9.0000000000000012] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022] Open
|
|
28
|
Huang H, Ning M, Liu J, Chen J, Feng J, Dai Y, Hu Y, Zhou YH. Is hepatitis B antigen in cord blood an immunotolerogen playing a critical role in the pathogenesis of chronic hepatitis B? Hum Vaccin Immunother 2019; 15:2192-2194. [PMID: 31099706 DOI: 10.1080/21645515.2019.1619409] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/26/2022] Open
Abstract
Recently, we showed that infants with or without fetal hepatitis B e antigen (HBeAg) exposure had comparable antibody response to hepatitis B vaccination and proposed that fetal HBeAg exposure appears to not induce immunotolerance to HBV. Here, we summarized the different results on the topic of fetal HBeAg exposure in inducing immunotolerance to HBV nucleocapsid protein, and the evidence to back up that the tendency of high infection rate in infants of HBeAg-positive mothers is more likely associated with higher maternal viral loads and is less likely associated with the fetal HBeAg exposure. We consider that whether fetal HBeAg exposure plays an important role in the pathogenesis of chronic HBV infection remains to be an open question.
Collapse
Affiliation(s)
- Hongyu Huang
- Department of Laboratory Medicine and Jiangsu Key Laboratory for Molecular Medicine, Nanjing Drum Tower Hospital, Nanjing University Medical School , Jiangsu , China
| | - Mingzhe Ning
- Department of Laboratory Medicine and Jiangsu Key Laboratory for Molecular Medicine, Nanjing Drum Tower Hospital, Nanjing University Medical School , Jiangsu , China
| | - Jingli Liu
- Department of Laboratory Medicine and Jiangsu Key Laboratory for Molecular Medicine, Nanjing Drum Tower Hospital, Nanjing University Medical School , Jiangsu , China
| | - Jie Chen
- Department of Obstetrics and Gynecology, Nanjing Drum Tower Hospital, Nanjing University Medical School , Jiangsu , China
| | - Jing Feng
- Department of Obstetrics and Gynecology, Nanjing Drum Tower Hospital, Nanjing University Medical School , Jiangsu , China
| | - Yimin Dai
- Department of Obstetrics and Gynecology, Nanjing Drum Tower Hospital, Nanjing University Medical School , Jiangsu , China
| | - Yali Hu
- Department of Obstetrics and Gynecology, Nanjing Drum Tower Hospital, Nanjing University Medical School , Jiangsu , China
| | - Yi-Hua Zhou
- Department of Laboratory Medicine and Jiangsu Key Laboratory for Molecular Medicine, Nanjing Drum Tower Hospital, Nanjing University Medical School , Jiangsu , China.,Department of Infectious Diseases, Nanjing Drum Tower Hospital, Nanjing Medical University , Jiangsu , China
| |
Collapse
|
|
29
|
Maraolo AE, Gentile I, Buonomo AR, Pinchera B, Borgia G. Current evidence on the management of hepatitis B in pregnancy. World J Hepatol 2018; 10:585-594. [PMID: 30310536 PMCID: PMC6177570 DOI: 10.4254/wjh.v10.i9.585] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2018] [Revised: 04/26/2018] [Accepted: 06/09/2018] [Indexed: 02/06/2023] Open
Abstract
Hepatitis B virus (HBV) infection is one of the main public health problems across the globe, since almost one third of the world population presents serological markers of contact with the virus. A profound impact on the epidemiology has been exerted by universal vaccination programmes in many countries, nevertheless the infection is still widespread also in its active form. In the areas of high endemicity (prevalence of hepatitis B surface antigen positivity > 7%), mother-to-child transmission represents the main modality of infection spread. That makes the correct management of HBV in pregnancy a matter of utmost importance. Furthermore, the infection in pregnancy needs to be carefully assessed and handled not only with respect to the risk of vertical transmission but also with respect to gravid women health. Each therapeutic or preventive choice deserves to be weighed upon attentively. On many aspects evidence is scarce or controversial. This review will highlight the latest insights into the paramount steps in managing HBV in pregnancy, with particular attention to recommendations from recent guidelines and data from up-do-date research syntheses.
Collapse
Affiliation(s)
- Alberto Enrico Maraolo
- Section of Infectious Diseases, Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples 80131, Italy
| | - Ivan Gentile
- Section of Infectious Diseases, Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples 80131, Italy
| | - Antonio Riccardo Buonomo
- Section of Infectious Diseases, Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples 80131, Italy
| | - Biagio Pinchera
- Section of Infectious Diseases, Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples 80131, Italy
| | - Guglielmo Borgia
- Section of Infectious Diseases, Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples 80131, Italy
| |
Collapse
|
|
30
|
Xu C, Liu J, Liu L, Bi Y, Xu B, Chen J, Xu B, Chen T, Hu Y, Zhou YH. Comparison of hepatitis B viral loads and viral antigen levels in child-bearing age women with and without pregnancy. BMC Pregnancy Childbirth 2018; 18:292. [PMID: 29980185 PMCID: PMC6035447 DOI: 10.1186/s12884-018-1932-9] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2018] [Accepted: 07/02/2018] [Indexed: 12/30/2022] Open
Abstract
BACKGROUND Pregnancy is a unique physiological condition with the cellular immune functions compromised at some extents to allow the mature of growing fetus. Whether pregnancy may influence the replication of hepatitis B virus (HBV) is less studied. The present study aimed to investigate the influence of pregnancy on the replication of HBV and expression of viral antigens by comparing the levels of HBV DNA and viral antigens in pregnant and non-pregnant women. METHODS A total of 727 HBsAg-positive serum samples, collected from 214 pregnant women and 513 non-pregnant women of childbearing age, were included. Based on the pregnancy status, subjects were divided into four groups: nulliparous (n = 158), pregnant (n = 214), 7-12 months postpartum (n = 170), and 2-5 years postpartum (n = 185). The levels of hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) were quantitatively measured with microparticle enzyme immunoassay. HBV DNA levels were detected by fluorescent real-time PCR. RESULTS The median ages of four groups were 25.0, 25.3, 26.2 and 29.3 years, respectively (p < 0.01). HBeAg-positive proportions were 34.2, 33.6, 35.3 and 29.2%, respectively (p = 0.624). HBV DNA levels in HBeAg-positive women were higher than those in HBeAg-negative women (7.88 vs 2.62 log IU/ml, p < 0.001). HBV DNA levels in the four groups with positive HBeAg were 7.8, 7.7, 8.0 and 8.0 log IU/ml, respectively (p = 0.057), while HBsAg titers were 4.4, 4.5, 4.6 and 4.8 log IU/ml (p = 0.086) and HBeAg titers were 3.1, 3.0, 3.1 and 3.0 log S/CO (p = 0.198). In the four groups with negative HBeAg, HBV DNA levels were 2.3, 2.6, 2.5 and 2.8 log IU/ml, respectively (p = 0.085), while HBsAg titers were 3.1, 3.3, 3.3 and 3.0 log IU/ml (p = 0.06). CONCLUSIONS Serum levels of HBV DNA and viral antigens showed no significant changes in nulliparous, pregnant, and postpartum women, regardless of the HBeAg status. The results indicate that pregnancy has little influence on the replication of HBV and the expression of viral antigens.
Collapse
Affiliation(s)
- Chenyu Xu
- Department of Obstetrics and Gynecology, Zhenjiang Fourth People's Hospital, Zhenjiang, 212001, Jiangsu, China
| | - Jingli Liu
- Departments of Laboratory Medicine and Infectious Diseases, Nanjing Drum Tower Hospital and Jiangsu Key Laboratory for Molecular Medicine, Nanjing University Medical School, 321 Zhongshan Road, Nanjing, 210008, Jiangsu, China
| | - Lanhua Liu
- Department of Obstetrics and Gynecology, Taixing People's Hospital, Taixing, 225400, Jiangsu, China
| | - Yongchun Bi
- Departments of Laboratory Medicine and Infectious Diseases, Nanjing Drum Tower Hospital and Jiangsu Key Laboratory for Molecular Medicine, Nanjing University Medical School, 321 Zhongshan Road, Nanjing, 210008, Jiangsu, China
| | - Biyun Xu
- Department of Biostatistics, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, 210008, Jiangsu, China
| | - Jie Chen
- Department of Obstetrics and Gynecology, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, 210008, Jiangsu, China
| | - Biao Xu
- Department of Obstetrics and Gynecology, Taixing People's Hospital, Taixing, 225400, Jiangsu, China
| | - Tingmei Chen
- Department of Obstetrics and Gynecology, Zhenjiang Fourth People's Hospital, Zhenjiang, 212001, Jiangsu, China
| | - Yali Hu
- Department of Obstetrics and Gynecology, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, 210008, Jiangsu, China
| | - Yi-Hua Zhou
- Departments of Laboratory Medicine and Infectious Diseases, Nanjing Drum Tower Hospital and Jiangsu Key Laboratory for Molecular Medicine, Nanjing University Medical School, 321 Zhongshan Road, Nanjing, 210008, Jiangsu, China. .,Department of Infectious Diseases, Nanjing Drum Tower Hospital, Nanjing Medical University, Nanjing, 210008, Jiangsu, China.
| |
Collapse
|
|
31
|
Chen T, Wang J, Qiu H, Yu Q, Yan T, Qi C, Cao F, Tian Z, Guo D, Yao N, Yang Y, He Y, Zhao Y, Liu J. Different interventional criteria for chronic hepatitis B pregnant women with HBeAg(+) or HBeAg(-): Epidemiological data from Shaanxi, China. Medicine (Baltimore) 2018; 97:e11406. [PMID: 29979437 PMCID: PMC6076167 DOI: 10.1097/md.0000000000011406] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/25/2022] Open
Abstract
The seroprevalence of hepatitis B virus (HBV) and its impact on pregnancy outcomes of women from Shaanxi Province (China) was assessed. Risk factors for mother-to-child transmission (MTCT) were evaluated based on HBV-related seroprevalence data.Viral markers and biochemical parameters were assessed in HBsAg-positive mothers and their infants out of 13,451 cases recruited. A pretested and structured questionnaire was used to test the general HBV knowledge. Descriptive statistics and logistic regression analysis were done to reveal possible risk factors for MTCT.The overall prevalence of HBsAg in pregnant women was 7.07% (951/13,451), and a rate as high as 9.40% was observed. Among the HBsAg-positive pregnant women, 30.49% (290/951) were HBeAg-positive, 22.08% (210/951) had HBV DNA levels >10 IU/mL and only 16.19% with a high risk of MTCT (34/210) had received antiviral treatment. The overall MTCT rate was 5.21%. Noteworthy, the risk ratio and 95% confidence interval (95% CI) of MTCT in HBeAg-negative mothers with HBV DNA levels >2 × 10 IU/mL and HBsAg >10 IU/mL was 26.062 (2.633-258.024), which was significantly higher than that of HBeAg-positive mothers with HBV DNA level >10 IU/mL. Moreover, the awareness and knowledge about HBV transmission, risk factors, and intervention for MTCT were generally lacking among HBsAg-positive mothers.As a higher HBsAg seroprevalence and a higher MTCT rate among HBeAg-negative mothers with lower HBV DNA level was observed, our study emphasizes different interventional criteria for HBeAg-positive and HBeAg-negative mothers. Extensive health education, routine screening, and immunization against HBV during pregnancy are highly warranted to minimize the possibility of perinatal transmission.
Collapse
Affiliation(s)
- Tianyan Chen
- Department of Infectious Diseases Department of Rheumatology and Immunology, the First Affiliated Hospital, Xi'an Jiaotong University Obstetric Department, Northwest Women's and Children's Hospital Department of Pediatric Surgery, the Second Affiliated Hospital Department of Gynaecology and Obstetrics Department of Neonatology, the First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi Province, China
| | | | | | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
32
|
Thilakanathan C, Wark G, Maley M, Davison S, Lawler J, Lee A, Shackel N, Nguyen V, Jackson K, Glass A, Locarnini SA, Levy MT. Mother-to-child transmission of hepatitis B: Examining viral cut-offs, maternal HBsAg serology and infant testing. Liver Int 2018. [PMID: 29532580 DOI: 10.1111/liv.13736] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
BACKGROUND & AIMS Antipartum antiviral therapy in the setting of high viral load is recommended to prevent mother-to-child transmission of hepatitis B although recommended viral load cut-offs vary. Quantitative HBsAg has been proposed as an alternative screening strategy to identify high viral load in this setting. Guidelines suggest testing all infants for vaccine response and infection. We set out to re-examine viral load cut-offs; the predictive value of quantitative HBsAg and the need for follow-up infant testing in our cohort. METHODS A retrospective cohort study of 469 HBsAg positive mother-baby pairs from 2 tertiary hospitals in Sydney was performed. Antiviral therapy (lamivudine or tenofovir disoproxil fumarate) was offered to women with viral load ≥6 log10 IU/mL (high) from 32 weeks gestation. Transmission and vaccine response was analysed according to viral load. The utility of quantitative HBsAg in identifying high viral load was examined. RESULTS Mother-to-child transmission only occurred in setting of high viral load, in 0.85% (1/117) of those who received antiviral therapy and in 8.66% (2/23) of those who chose not to. Quantitative HBsAg did not accurately identify high-risk mothers HBV DNA ≥6 log10 IU/mL. Successful infant vaccine response was 98.7% overall, and 99.4% when viral load was <6 log10 IU/mL. CONCLUSION Antiviral therapy initiated at 32 weeks when maternal viral load is ≥6 log10 IU/mL almost completely abrogates transmission. Quantitative HBsAg does not reliably predict high viral load. When maternal viral load is <6 log10 IU/mL, high vaccine efficacy and zero transmission suggests testing infants is of little value.
Collapse
Affiliation(s)
- Cynthuja Thilakanathan
- Department of Gastroenterology and Liver, Liverpool Hospital, Sydney, NSW, Australia.,University of New South Wales, Sydney, NSW, Australia.,Ingham Institute, Sydney, NSW, Australia
| | - Gabrielle Wark
- Department of Gastroenterology and Liver, Liverpool Hospital, Sydney, NSW, Australia
| | - Michael Maley
- Department of Gastroenterology and Liver, Liverpool Hospital, Sydney, NSW, Australia.,University of New South Wales, Sydney, NSW, Australia.,Department of Microbiology and Infectious Diseases, NSW Health Pathology, Liverpool, NSW, Australia
| | - Scott Davison
- Department of Gastroenterology and Liver, Liverpool Hospital, Sydney, NSW, Australia
| | | | - Aimei Lee
- Department of Gastroenterology and Liver, Liverpool Hospital, Sydney, NSW, Australia.,University of New South Wales, Sydney, NSW, Australia.,Ingham Institute, Sydney, NSW, Australia
| | - Nicholas Shackel
- Department of Gastroenterology and Liver, Liverpool Hospital, Sydney, NSW, Australia.,University of New South Wales, Sydney, NSW, Australia.,Ingham Institute, Sydney, NSW, Australia
| | - Vi Nguyen
- Department of Gastroenterology and Liver, Liverpool Hospital, Sydney, NSW, Australia
| | - Kathy Jackson
- Victorian Infectious Diseases Reference Laboratory, WHO Regional Reference Laboratory for Hepatitis B, Doherty Institute, Melbourne, VIC, Australia
| | - Anne Glass
- Department of Gastroenterology and Liver, Liverpool Hospital, Sydney, NSW, Australia
| | - Stephen A Locarnini
- Victorian Infectious Diseases Reference Laboratory, WHO Regional Reference Laboratory for Hepatitis B, Doherty Institute, Melbourne, VIC, Australia
| | - Miriam T Levy
- Department of Gastroenterology and Liver, Liverpool Hospital, Sydney, NSW, Australia.,University of New South Wales, Sydney, NSW, Australia.,Ingham Institute, Sydney, NSW, Australia
| |
Collapse
|
|
33
|
Hu Y, Xu C, Xu B, Hu L, Liu Q, Chen J, Liu J, Liu L, Yang J, Chen T, Wen J, Jiang N, Zhang Y, Cao M, Feng J, Lin X, Wang Z, Xu B, Zhou YH. Safety and efficacy of telbivudine in late pregnancy to prevent mother-to-child transmission of hepatitis B virus: A multicenter prospective cohort study. J Viral Hepat 2018; 25:429-437. [PMID: 29193547 DOI: 10.1111/jvh.12834] [Citation(s) in RCA: 54] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 10/14/2017] [Indexed: 12/12/2022]
Abstract
Infection of hepatitis B virus (HBV) occurs in ~10% of infants of HBV-infected mothers with positive hepatitis B e antigen (HBeAg) after immunoprophylaxis. We aimed to evaluate the safety and efficacy of telbivudine used during late pregnancy for preventing mother-to-child transmission of HBV. We conducted a multicenter prospective cohort study in 5 hospitals from 2012 to 2014, which enrolled HBV-infected singleton pregnant women with positive HBeAg. By their choice, women were divided into therapy (telbivudine 600 mg/day, from gestation 28-32 weeks to 3-4 weeks postpartum) and control (no antiviral agent) groups. Infants received passive-active immunoprophylaxis and follow-up at the age of 7-14 months. Totally, 328 pregnant women were included: 149 in the telbivudine group and 179 in the control group. Baseline HBV DNA levels were similar in the 2 groups (7.43 vs 7.37 log10 IU/mL, P = .711). At delivery, HBV DNA levels in the telbivudine and control groups were 3.80 and 7.26 log10 IU/mL, respectively (P < .0001). Of the infants, 128 (85.9%) in the telbivudine group and 156 (87.2%) in the control group were followed up. No infant in the telbivudine group had chronic infection, while 2 (1.28%) infants in the control group did (P = .503). Three (2.34%) infants in the telbivudine group, but none in the control group, had severe congenital or developmental abnormalities (P = .090). The data indicate that telbivudine may block perinatal HBV transmission. However, larger studies are required to clarify whether anti-HBV therapy in pregnancy is associated with severe adverse effects in the foetuses and infants.
Collapse
Affiliation(s)
- Y Hu
- Department of Obstetrics and Gynecology, Jiangsu Key Laboratory for Molecular Medicine, Nanjing Drum Tower Hospital, Nanjing University Medical School, Jiangsu, China
| | - C Xu
- Department of Obstetrics and Gynecology, Zhenjiang Fourth People's Hospital, Jiangsu, China
| | - B Xu
- Department of Obstetrics and Gynecology, Taixing People's Hospital, Jiangsu, China
| | - L Hu
- Department of Obstetrics and Gynecology, Wuxi Maternal and Child Health Hospital, Jiangsu, China
| | - Q Liu
- Department of Obstetrics and Gynecology, Kunshan First People's Hospital, Jiangsu, China
| | - J Chen
- Department of Obstetrics and Gynecology, Jiangsu Key Laboratory for Molecular Medicine, Nanjing Drum Tower Hospital, Nanjing University Medical School, Jiangsu, China
| | - J Liu
- Department of Laboratory Medicine, Jiangsu Key Laboratory for Molecular Medicine, Nanjing Drum Tower Hospital, Nanjing University Medical School, Jiangsu, China
| | - L Liu
- Department of Obstetrics and Gynecology, Taixing People's Hospital, Jiangsu, China
| | - J Yang
- Department of Obstetrics and Gynecology, Taixing People's Hospital, Jiangsu, China
| | - T Chen
- Department of Obstetrics and Gynecology, Zhenjiang Fourth People's Hospital, Jiangsu, China
| | - J Wen
- Department of Obstetrics and Gynecology, Zhenjiang Fourth People's Hospital, Jiangsu, China
| | - N Jiang
- Department of Obstetrics and Gynecology, Kunshan First People's Hospital, Jiangsu, China
| | - Y Zhang
- Department of Obstetrics and Gynecology, Kunshan First People's Hospital, Jiangsu, China
| | - M Cao
- Department of Obstetrics and Gynecology, Wuxi Maternal and Child Health Hospital, Jiangsu, China
| | - J Feng
- Department of Obstetrics and Gynecology, Jiangsu Key Laboratory for Molecular Medicine, Nanjing Drum Tower Hospital, Nanjing University Medical School, Jiangsu, China
| | - X Lin
- Department of Obstetrics and Gynecology, Jiangsu Key Laboratory for Molecular Medicine, Nanjing Drum Tower Hospital, Nanjing University Medical School, Jiangsu, China
| | - Z Wang
- Department of Obstetrics and Gynecology, Jiangsu Key Laboratory for Molecular Medicine, Nanjing Drum Tower Hospital, Nanjing University Medical School, Jiangsu, China
| | - B Xu
- Department of Biostatistics, Nanjing Drum Tower Hospital, Nanjing University Medical School, Jiangsu, China
| | - Y-H Zhou
- Department of Laboratory Medicine, Jiangsu Key Laboratory for Molecular Medicine, Nanjing Drum Tower Hospital, Nanjing University Medical School, Jiangsu, China.,Department of Infectious Diseases, Nanjing Drum Tower Hospital, Nanjing University Medical School, Jiangsu, China
| |
Collapse
|
|
34
|
Arora A, Singh SP, Kumar A, Saraswat VA, Aggarwal R, Bangar M, Bhaumik P, Devarbhavi H, Dhiman RK, Dixit VK, Goel A, Goswami B, Kapoor D, Madan K, Narayan J, Nijhawan S, Pandey G, Rai RR, Sahu MK, Saraf N, Shalimar, Shenoy T, Thomas V, Wadhawan M. INASL Position Statements on Prevention, Diagnosis and Management of Hepatitis B Virus Infection in India: The Andaman Statements. J Clin Exp Hepatol 2018; 8:58-80. [PMID: 29743798 PMCID: PMC5938334 DOI: 10.1016/j.jceh.2017.12.001] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/02/2017] [Accepted: 12/09/2017] [Indexed: 12/12/2022] Open
Abstract
Hepatitis B Virus (HBV) infection is one of the major causes of morbidity, mortality and healthcare expenditure in India. There are no Indian consensus guidelines on prevention, diagnosis and management of HBV infection. The Indian National Association for Study of the Liver (INASL) set up a taskforce on HBV in 2016, with a mandate to develop consensus guidelines for diagnosis and management of HBV infection, relevant to disease patterns and clinical practices in India. The taskforce first identified contentious issues on various aspects of HBV management, which were allotted to individual members of the taskforce who reviewed them in detail. A 2-day round table discussion was held on 11th and 12th February 2017 at Port Blair, Andaman & Nicobar Islands, to discuss, debate, and finalize the consensus statements. The members of the taskforce reviewed and discussed the existing literature threadbare at this meeting and formulated the 'INASL position statements' on each of the issues. The evidence and recommendations in these guidelines have been graded according to the Grading of Recommendations Assessment Development and Evaluation (GRADE) system with minor modifications. The strength of recommendations (strong: 1, weak: 2) thus reflects the quality (grade) of underlying evidence (A, B, C, D). We present here the INASL position statements on prevention, diagnosis and management of HBV in India.
Collapse
Key Words
- AASLD, American Association for the Study of Liver Diseases
- ADV, adefovir dipivoxil
- ALT, alanine aminotransferase
- APASL, Asian Pacific Association for the Study of the Liver
- ART, antiretroviral therapy
- AST, aspartate aminotransferase
- Anti-HBe, antibodies to hepatitis B envelope antigen
- CBC, complete blood count
- CDC, Center for Disease Control
- CHB, chronic hepatitis B
- CU-HCC, Chinese University-Hepatocellular Carcinoma
- DAA, direct-acting antiviral
- DILI, drug induced liver injury
- DNA, deoxyribonucleic acid
- EASL, European Association for the Study of the Liver
- ETV, entecavir
- GAG-HCC, Guide with Age, Gender, HBV DNA, Core Promoter Mutations and Cirrhosis-Hepatocellular Carcinoma
- GGT, gamma-glutamyl transferase
- GRADE, Grading of Recommendations Assessment Development and Evaluation
- HBIG, hepatitis B immune globulin
- HBV, hepatitis B virus
- HBeAg, hepatitis B envelope antigen
- HCC, hepatocellular carcinoma
- HCV, hepatitis C virus
- HDV, hepatitis D virus
- HIV, human immunodeficiency virus
- IFN-α, interferon alpha
- INASL, Indian National Association for Study of the Liver
- INR, international normalized ratio
- KASL, Korean Association for the Study of the Liver
- LAM, lamivudine
- NA, nucleos(t)ide analogue
- PAGE-B, platelets, age, gender—hepatitis B
- PVNR, primary virological non-response
- PVR, partial virological response
- PegIFN-α, pegylated interferon alpha
- RCT, randomized controlled trial
- REACH-B, risk estimation for hepatocellular carcinoma in chronic hepatitis B
- SOVR, sustained off-therapy virological response
- TAF, tenofovir alafenamide
- TDF, tenofovir disoproxil fumarate
- TDV, telbivudine
- TSH, thyroid-stimulating hormone
- VR, virologic response
- WHO, World Health Organization
- anti-HBs, antibody to hepatitis B surface antigen
- cccDNA, covalently closed circular DNA
- chronic hepatitis
- cirrhosis
- eGFR, estimated glomerular filtration rate
- hepatitis B
- jaundice
- liver failure
Collapse
Affiliation(s)
- Anil Arora
- Director, Institute of Liver, Gastroenterology, and Pancreatico-Biliary Sciences, Ganga Ram Institute for Postgraduate Medical Education & Research (GRIPMER), Sir Ganga Ram Hospital, New Delhi, India
| | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
35
|
Lu Y, Zhu FC, Liu JX, Zhai XJ, Chang ZJ, Yan L, Wei KP, Zhang X, Zhuang H, Li J. The maternal viral threshold for antiviral prophylaxis of perinatal hepatitis B virus transmission in settings with limited resources: A large prospective cohort study in China. Vaccine 2017; 35:6627-6633. [PMID: 29079104 DOI: 10.1016/j.vaccine.2017.10.032] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2017] [Revised: 10/04/2017] [Accepted: 10/12/2017] [Indexed: 12/12/2022]
Abstract
BACKGROUND Antiviral therapy has been documented to reduce perinatal transmission of hepatitis B virus (HBV) in highly viremic mothers. This large prospective cohort study conducted in China aims to delineate the maternal viral threshold for consideration of antiviral prophylaxis in settings with limited resources. METHODS A total of 1177 mother-infant pairs with positive maternal hepatitis B surface antigen (HBsAg) under current passive-active prophylaxis regimen were enrolled from community health centers in Jiangsu and Henan provinces, China. Maternal hepatitis B e antigen (HBeAg) status and viral load were tested at 36-40 weeks of gestation. Post-vaccination serologic testing was performed at 7 and 12 months of age. RESULTS HBeAg-positive mothers (419/1177; 35.6%) had significantly higher viral loads, compared with HBeAg-negative mothers (758/1177; 64.4%) (8.12 vs. 2.69 log IU/mL, p < .0001). Twenty infants, born to HBeAg-positive mothers with high viral loads (median, 8.38; range: 7.82-9.22 log IU/mL), were infected at 7 months of age. In contrast, none of the HBeAg-negative mothers transmitted HBV to their offspring. After adjustment for the other risk factor, a higher maternal viral load was significantly associated with a higher risk of transmission (adjusted odds ratio, 3.78; 95% confidence interval: 1.46-9.81; p = .006). The rates of passive-active immunoprophylaxis failure were 0.0% (0/789), 0.0% (0/27), 0.0% (0/32) and 6.1% (20/329) at maternal viral loads of <5, 5-6, 6-7 and ≥7 log IU/mL, respectively. The antibody to hepatitis B surface antigen (anti-HBs) response rate was 98.4% (1138/1157) at 7 months of age. CONCLUSIONS Results from this study indicate that the maternal viral threshold associated with perinatal transmission of HBV is 7 log IU/mL, which may be appropriate for consideration of antiviral prophylaxis in settings with limited resources.
Collapse
Affiliation(s)
- Ying Lu
- Department of Microbiology and Center of Infectious Diseases, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China
| | - Feng-Cai Zhu
- Department of Infectious Diseases, Jiangsu Provincial Center for Disease Control and Prevention, Nanjing 210009, China
| | - Jian-Xun Liu
- Department of Major Projects, Zhengzhou Municipal Center for Disease Control and Prevention, Zhengzhou 450053, China
| | - Xiang-Jun Zhai
- Department of Infectious Diseases, Jiangsu Provincial Center for Disease Control and Prevention, Nanjing 210009, China
| | - Zhan-Jun Chang
- Department of Major Projects, Zhengzhou Municipal Center for Disease Control and Prevention, Zhengzhou 450053, China
| | - Ling Yan
- Department of Microbiology and Center of Infectious Diseases, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China
| | - Kai-Ping Wei
- Department of Microbiology and Center of Infectious Diseases, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China
| | - Xin Zhang
- Department of Microbiology and Center of Infectious Diseases, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China
| | - Hui Zhuang
- Department of Microbiology and Center of Infectious Diseases, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China.
| | - Jie Li
- Department of Microbiology and Center of Infectious Diseases, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China.
| |
Collapse
|
|
36
|
Lampertico P, Agarwal K, Berg T, Buti M, Janssen HL, Papatheodoridis G, Zoulim F, Tacke F. EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection. J Hepatol 2017; 67:370-398. [PMID: 28427875 DOI: 10.1016/j.jhep.2017.03.021] [Citation(s) in RCA: 3641] [Impact Index Per Article: 455.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/23/2017] [Accepted: 03/23/2017] [Indexed: 02/07/2023]
Abstract
Hepatitis B virus (HBV) infection remains a global public health problem with changing epidemiology due to several factors including vaccination policies and migration. This Clinical Practice Guideline presents updated recommendations for the optimal management of HBV infection. Chronic HBV infection can be classified into five phases: (I) HBeAg-positive chronic infection, (II) HBeAg-positive chronic hepatitis, (III) HBeAg-negative chronic infection, (IV) HBeAg-negative chronic hepatitis and (V) HBsAg-negative phase. All patients with chronic HBV infection are at increased risk of progression to cirrhosis and hepatocellular carcinoma (HCC), depending on host and viral factors. The main goal of therapy is to improve survival and quality of life by preventing disease progression, and consequently HCC development. The induction of long-term suppression of HBV replication represents the main endpoint of current treatment strategies, while HBsAg loss is an optimal endpoint. The typical indication for treatment requires HBV DNA >2,000IU/ml, elevated ALT and/or at least moderate histological lesions, while all cirrhotic patients with detectable HBV DNA should be treated. Additional indications include the prevention of mother to child transmission in pregnant women with high viremia and prevention of HBV reactivation in patients requiring immunosuppression or chemotherapy. The long-term administration of a potent nucleos(t)ide analogue with high barrier to resistance, i.e., entecavir, tenofovir disoproxil or tenofovir alafenamide, represents the treatment of choice. Pegylated interferon-alfa treatment can also be considered in mild to moderate chronic hepatitis B patients. Combination therapies are not generally recommended. All patients should be monitored for risk of disease progression and HCC. Treated patients should be monitored for therapy response and adherence. HCC remains the major concern for treated chronic hepatitis B patients. Several subgroups of patients with HBV infection require specific focus. Future treatment strategies to achieve 'cure' of disease and new biomarkers are discussed.
Collapse
|
|
37
|
Chen ZX, Gu GF, Bian ZL, Cai WH, Shen Y, Hao YL, Zhang S, Shao JG, Qin G. Clinical course and perinatal transmission of chronic hepatitis B during pregnancy: A real-world prospective cohort study. J Infect 2017; 75:146-154. [DOI: 10.1016/j.jinf.2017.05.012] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2016] [Revised: 03/27/2017] [Accepted: 05/11/2017] [Indexed: 01/24/2023]
|
|
38
|
Lu Y, Liang XF, Wang FZ, Yan L, Li RC, Li YP, Zhu FC, Zhai XJ, Li J, Zhuang H. Hepatitis B vaccine alone may be enough for preventing hepatitis B virus transmission in neonates of HBsAg (+)/HBeAg (-) mothers. Vaccine 2016; 35:40-45. [PMID: 27894717 DOI: 10.1016/j.vaccine.2016.11.061] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2016] [Revised: 11/14/2016] [Accepted: 11/15/2016] [Indexed: 01/09/2023]
Abstract
BACKGROUND AND AIM To prospectively evaluate the efficacy of vaccine alone compared with vaccine plus HBIG for preventing HBV transmission in neonates of HBsAg (+)/HBeAg (-) mothers. METHODS Combined immunization is currently recommended for neonates of HBsAg (+) mothers in China. As a result, a randomized design is infeasible due to ethical reasons. In practice, Guangxi Zhuang Autonomous Region and Jiangsu Province implement vaccine alone and vaccine plus HBIG strategies for neonates born to HBsAg (+)/HBeAg (-) mothers, respectively. We alternatively enrolled neonates of HBsAg (+)/HBeAg (-) mothers from these two regions. Three doses of a recombinant yeast-derived hepatitis B vaccine were given at 0, 1 and 6months with or without HBIG at birth. RESULTS At 7months, sera were collected from 132 neonates in Guangxi Zhuang Autonomous Region and 752 neonates in Jiangsu Province. Baseline characteristics of both mothers and neonates were comparable in the two regions. No differences were revealed regarding the occurrence of perinatal HBV transmission with or without HBIG at birth [0.1% (1/752) vs. 0.0% (0/132), p=1.000]. The anti-HBs response rates were 97.7% (129/132) and 98.5% (740/751) for the neonates with vaccine alone and with HBIG (p=0.758), respectively. Vaccine alone induced a significantly higher anti-HBs GMC as compared to vaccine plus HBIG at 7months of age (1555.3mIU/mL vs. 654.9mIU/mL, p<0.0001). At 12months of age, protective levels of anti-HBs remained in 97.4% (596/612) and 98.3% (118/120) of the neonates receiving and not receiving HBIG, respectively (p=0.771). The neonates receiving combined prophylaxis had a markedly lower anti-HBs GMC (210.7mIU/mL vs. 297.0mIU/mL, p=0.011). Horizontal HBV transmission occurred in none of the successfully immunized neonates for both compared groups at 12months of age. CONCLUSIONS Vaccine alone may be enough for preventing HBV transmission in neonates of HBsAg (+)/HBeAg (-) mothers.
Collapse
Affiliation(s)
- Ying Lu
- Department of Microbiology and Center of Infectious Diseases, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China
| | - Xiao-Feng Liang
- Chinese Center for Disease Control and Prevention, Beijing 102206, China
| | - Fu-Zhen Wang
- Chinese Center for Disease Control and Prevention, Beijing 102206, China
| | - Ling Yan
- Department of Microbiology and Center of Infectious Diseases, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China
| | - Rong-Cheng Li
- Guangxi Zhuang Autonomous Region Center for Disease Control and Prevention, Nanning 530028, China
| | - Yan-Ping Li
- Guangxi Zhuang Autonomous Region Center for Disease Control and Prevention, Nanning 530028, China
| | - Feng-Cai Zhu
- Department of Infectious Disease, Jiangsu Provincial Center for Disease Control and Prevention, Nanjing 210009, China
| | - Xiang-Jun Zhai
- Department of Infectious Disease, Jiangsu Provincial Center for Disease Control and Prevention, Nanjing 210009, China
| | - Jie Li
- Department of Microbiology and Center of Infectious Diseases, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China.
| | - Hui Zhuang
- Department of Microbiology and Center of Infectious Diseases, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China.
| |
Collapse
|
|
39
|
Dusheiko G, Easterbrook P. Bringing to an end mother-to-child transmission of hepatitis B: A role for quantitative hepatitis B surface antigen? Hepatology 2016; 64:1408-1410. [PMID: 27452950 DOI: 10.1002/hep.28732] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/28/2016] [Accepted: 07/22/2016] [Indexed: 12/11/2022]
Affiliation(s)
- Geoffrey Dusheiko
- University College London Medical School and Kings College Hospital, London, United Kingdom.
| | - Philippa Easterbrook
- Global Hepatitis Program, HIV Department World Health Organization, Geneva, Switzerland
| |
Collapse
|
|
40
|
Samadi Kochaksaraei G, Congly SE, Matwiy T, Castillo E, Martin SR, Charlton CL, Coffin CS. Cost-effectiveness of quantitative hepatitis B virus surface antigen testing in pregnancy in predicting vertical transmission risk. Liver Int 2016; 36:1604-1610. [PMID: 27059287 DOI: 10.1111/liv.13139] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/13/2016] [Accepted: 03/26/2016] [Indexed: 12/13/2022]
Abstract
BACKGROUND & AIMS Vertical transmission of hepatitis B virus (HBV) can occur despite immunoprophylaxis in mothers with high HBV DNA levels (>5-7 log10 IU/ml). Quantitative hepatitis B surface antigen (qHBsAg) testing could be used as a surrogate marker to identify high viral load carriers, but there is limited data in pregnancy. We conducted a prospective observational study to determine the cost-effectiveness and utility of qHBsAg as a valid surrogate marker of HBV DNA. METHODS Pregnant patients with chronic hepatitis B were recruited from a tertiary referral centre. HBV DNA levels and qHBsAg were assessed in the second to third trimester. Statistical analysis was performed by Spearman's rank correlation and student's t-test. The cost-effectiveness of qHBsAg as compared to HBV DNA testing was calculated. RESULTS Ninety nine women with 103 pregnancies, median age 32 years, 65% Asian, 23% African and 12% other [Hispanic, Caucasian] were enrolled. Overall, 23% (23/99) were HBV e Ag (HBeAg)-positive. A significant correlation between qHBsAg and HBV DNA levels was noted in HBeAg-positive patients (r = 0.79, P < 0.05) but not in HBeAg-negative patients (r = 0.17, P = 0.06). In receiver operating characteristic analysis, the optimal qHBsAg cut-off values for predicting maternal viraemia associated with immunoprophylaxis failure (i.e., HBV DNA ≥7 log10 IU/ml) was 4.3 log10 IU/ml (accuracy 98.7%, sensitivity 94.7%, specificity 94.4%) (95% CI, 97-100%, P < 0.05). Use of HBV DNA as compared to qHBsAg costs approximately $20 000 more per infection prevented. CONCLUSION In resource poor regions, qHBsAg could be used as a more cost-effective marker for high maternal viraemia, and indicate when anti-HBV nucleos/tide analogue therapy should be used to prevent HBV immunoprophylaxis failure.
Collapse
Affiliation(s)
| | - Stephen E Congly
- Department of Medicine, University of Calgary, Calgary, AB, Canada
| | - Trudy Matwiy
- Department of Medicine, University of Calgary, Calgary, AB, Canada
| | - Eliana Castillo
- Department of Medicine, University of Calgary, Calgary, AB, Canada
| | - Steven R Martin
- Department of Pediatrics, Alberta Children's Hospital, University of Calgary, Calgary, AB, Canada
| | - Carmen L Charlton
- Provincial Laboratory for Public Health (ProvLab), University of Alberta Hospital, Edmonton, AB, Canada.,Laboratory Medicine and Pathology, University of Alberta, Edmonton, AB, Canada
| | - Carla S Coffin
- Department of Medicine, University of Calgary, Calgary, AB, Canada.
| |
Collapse
|
|
41
|
Wen WH, Huang CW, Chie WC, Yeung CY, Zhao LL, Lin WT, Wu JF, Ni YH, Hsu HY, Chang MH, Lin LH, Chen HL. Quantitative maternal hepatitis B surface antigen predicts maternally transmitted hepatitis B virus infection. Hepatology 2016; 64:1451-1461. [PMID: 27044007 DOI: 10.1002/hep.28589] [Citation(s) in RCA: 63] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/16/2015] [Revised: 03/23/2016] [Accepted: 03/27/2016] [Indexed: 12/20/2022]
Abstract
UNLABELLED Despite immunoprophylaxis, hepatitis B virus (HBV) transmission in highly viremic mothers remains a global health issue. Using quantitative maternal surface antigen (HBsAg) to predict HBV infection in infants has not been investigated. We enrolled 526 mother-infant pairs with positive maternal HBsAg under current immunoprophylaxis. Maternal viral load and quantitative HBsAg were measured in the peripartum period. Infant HBsAg seropositivity for more than 6 months was defined as chronic infection. Rates of chronic infection in infants at various maternal HBsAg levels were estimated using a multivariate logistic regression model. Results showed that maternal HBsAg was positively correlated with maternal viral load (r = 0.69; P < 0.001) and accurately predicted maternal viral load above 6, 7, and 8 log10 IU/mL with an area under the receiver operating characteristic curve (AUC) of 0.97, 0.98, and 0.95. Nineteen infants were chronically infected. After adjustment for the other risk factor, maternal HBsAg level was significantly associated with risk of infection (adjusted odds ratio for each log10 IU/mL increase, 15.02; 95% confidence interval [CI], 3.89-57.94; P < 0.001). The AUC for predicting infection by quantitative maternal HBsAg was comparable to that by maternal viral load (0.89 vs. 0.87; P = 0.459). Estimated rates of infection at maternal HBsAg levels of 4, 4.5, and 5 log10 IU/mL were 2.4% (95% CI, 0.1-4.6; P = 0.04), 8.6% (95% CI, 4.5-12.7; P < 0.001), and 26.4% (95% CI, 12.6-40.2; P < 0.001). CONCLUSION Quantitative maternal HBsAg predicts infection in infants as well as maternal viral load does. Antiviral therapy may be considered in pregnant women with an HBsAg level above 4-4.5 log10 IU/mL to interrupt mother-to-infant transmission. (Hepatology 2016;64:1451-1461).
Collapse
Affiliation(s)
- Wan-Hsin Wen
- Department of Pediatrics, Cardinal Tien Hospital, New Taipei City, Taiwan.,School of Medicine, College of Medicine, Fu-Jen Catholic University, New Taipei City, Taiwan
| | - Chi-Wen Huang
- Department of Pediatrics, Hospital and College of Medicine, National Taiwan University, Taipei, Taiwan.,Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan
| | - Wei-Chu Chie
- Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan
| | - Chun-Yan Yeung
- Department of Pediatrics, Mackay Memorial Hospital, Taipei, Taiwan
| | - Lu-Lu Zhao
- Department of Pediatrics, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City, Taiwan
| | - Wen-Terng Lin
- Department of Pediatrics, En Chu Kong Hospital, New Taipei City, Taiwan
| | - Jia-Feng Wu
- Department of Pediatrics, Hospital and College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Yen-Hsuan Ni
- Department of Pediatrics, Hospital and College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Hong-Yuan Hsu
- Department of Pediatrics, Hospital and College of Medicine, National Taiwan University, Taipei, Taiwan.,Department of Medical Education and Bioethics, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Mei-Hwei Chang
- Department of Pediatrics, Hospital and College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Lung-Huang Lin
- School of Medicine, College of Medicine, Fu-Jen Catholic University, New Taipei City, Taiwan. .,Department of Pediatrics, Cathay General Hospital, Taipei, Taiwan.
| | - Huey-Ling Chen
- Department of Pediatrics, Hospital and College of Medicine, National Taiwan University, Taipei, Taiwan. .,Department of Medical Education and Bioethics, College of Medicine, National Taiwan University, Taipei, Taiwan.
| |
Collapse
|
|
42
|
Liu J, Feng Y, Wang J, Li X, Lei C, Jin D, Feng W, Yang Y, He Y, Li Y, Du D, Zhang X, Jin L, Yan T, Chen T, Zhao Y. An "immune barrier" is formed in the placenta by hepatitis B immunoglobulin to protect the fetus from hepatitis B virus infection from the mother. Hum Vaccin Immunother 2016; 11:2068-76. [PMID: 26126021 PMCID: PMC4635728 DOI: 10.1080/21645515.2015.1010890] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
The effect of hepatitis B immunoglobulin (HBIG) on hepatitis B virus (HBV) DNA load and its protective mechanism are not well understood. Twenty-eight hepatitis B surface antigen (HBsAg)–positive pregnant women and their newborns were assigned to an experimental (n = 12) or control group (n = 16) according to whether they received HBIG during pregnancy. HBV DNA load and markers titer of the mothers and newborns were tested. These markers and HBV DNA load in mothers of the experimental group did not fluctuate significantly and were comparable to the control. In the experimental group, there was a positive correlation between mothers and their newborns with regard to hepatitis B surface antibody titer. Immunohistochemical staining of placenta sections showed that HBsAg-positive areas mainly included trophoblastic cells and villous mesenchymal cells without HBIG colocalization, whereas HBIG-positive areas principally included villous capillary endothelial cells and villous mesenchymal cells. Additionally, compared with the control group, the positive rate and mean density of HBIG in the experimental group were remarkably higher. HBIG deposition was seen in Hofbauer cells. Thus, rather than influencing virus replication, HBIG forms an immune barrier between the mother and fetus to prevent HBV transmission.
Collapse
Affiliation(s)
- Jinfeng Liu
- a Department of Infectious Diseases ; the First Affiliated Hospital of Medical College; Xi'an Jiaotong University ; Xi'an , Shaanxi Province , China
| | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
43
|
Terrault NA, Bzowej NH, Chang KM, Hwang JP, Jonas MM, Murad MH. AASLD guidelines for treatment of chronic hepatitis B. Hepatology 2016; 63:261-83. [PMID: 26566064 PMCID: PMC5987259 DOI: 10.1002/hep.28156] [Citation(s) in RCA: 1555] [Impact Index Per Article: 172.8] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/24/2015] [Accepted: 08/25/2015] [Indexed: 12/11/2022]
Affiliation(s)
| | | | - Kyong-Mi Chang
- Corporal Michael J. Crescenz VA Medical Center & University of Pennsylvania Perelman School of Medicine, Philadelphia, PA
| | - Jessica P Hwang
- The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Maureen M Jonas
- Boston Children's Hospital, Harvard Medical School, Boston, MA
| | | |
Collapse
|
|
44
|
Fujiko M, Chalid MT, Turyadi, Ie SI, Maghfira, Syafri, Wahyuni R, Roni M, Patellongi I, Massi MN, Muljono DH. Chronic hepatitis B in pregnant women: is hepatitis B surface antigen quantification useful for viral load prediction? Int J Infect Dis 2015; 41:83-9. [PMID: 26571304 DOI: 10.1016/j.ijid.2015.11.002] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2015] [Revised: 10/20/2015] [Accepted: 11/04/2015] [Indexed: 01/10/2023] Open
Abstract
BACKGROUND New cases of hepatitis B virus (HBV) infection continue to occur worldwide. Most of these are due to mother-to-child transmission (MTCT), with maternal viraemia as the most important contributing factor. The hepatitis B surface antigen (HBsAg) level, which correlates positively with viral load, has been used for treatment monitoring in chronic hepatitis B. This study evaluated the usefulness of quantitative HBsAg for viral load prediction in HBsAg-positive pregnant women. METHODS A total of 943 pregnant women in Makassar, Indonesia, were screened for HBsAg. Sixty-four women were HBsAg-positive and investigated. HBsAg level and hepatitis B e antigen (HBeAg)/hepatitis B e antibody (anti-HBe) status were determined serologically. Viral load was measured by real-time PCR. HBV DNA was sequenced and analysed for identification of genotype and basal core promoter (BCP)/precore (PC) mutations. RESULTS Of 64 subjects, 12 (18.8%) were HBeAg-positive and 52 (81.3%) were HBeAg-negative. HBsAg and HBV DNA levels were significantly higher in the HBeAg-positive group (p<0.001). HBsAg and HBV DNA levels were positively correlated in the HBeAg-positive group (r = 0.659; p=0.02), but not in the HBeAg-negative group (r=0.194; p=0.168). Low HBsAg levels (<3.0 log10 IU/ml) corresponded with HBV DNA levels<6.0 log10 IU/ml (r=0.404; p=0.001), a recognized threshold for MTCT. Genotype C was more prevalent than genotype B, but not associated with HBsAg level, viral load, or HBeAg status. Two-thirds of HBeAg-negative subjects with high HBV DNA levels harboured BCP (A1762T/G1764A) and/or PC (G1896A) variants. CONCLUSIONS HBsAg levels provide a good viral load predictor in HBeAg-positive but not HBeAg-negative pregnant women. The HBeAg-negative group had a frequent occurrence of BCP/PC variants, which may have contributed to the lack of correlation observed. Samples with a low HBsAg level, which is associated with a low risk of MTCT, do not require HBV DNA measurement.
Collapse
Affiliation(s)
- Masita Fujiko
- Faculty of Medicine, Hasanuddin University, Makassar, South Sulawesi, Indonesia
| | - Maisuri T Chalid
- Faculty of Medicine, Hasanuddin University, Makassar, South Sulawesi, Indonesia
| | - Turyadi
- Eijkman Institute for Molecular Biology, Jl. Diponegoro 69, Jakarta Pusat 10430, DKI Jakarta, Indonesia
| | - Susan I Ie
- Eijkman Institute for Molecular Biology, Jl. Diponegoro 69, Jakarta Pusat 10430, DKI Jakarta, Indonesia
| | - Maghfira
- Faculty of Medicine, Hasanuddin University, Makassar, South Sulawesi, Indonesia
| | - Syafri
- Faculty of Medicine, Hasanuddin University, Makassar, South Sulawesi, Indonesia
| | - Ridha Wahyuni
- Faculty of Medicine, Hasanuddin University, Makassar, South Sulawesi, Indonesia
| | - Martono Roni
- Eijkman Institute for Molecular Biology, Jl. Diponegoro 69, Jakarta Pusat 10430, DKI Jakarta, Indonesia
| | | | - M Nasrum Massi
- Faculty of Medicine, Hasanuddin University, Makassar, South Sulawesi, Indonesia
| | - David H Muljono
- Faculty of Medicine, Hasanuddin University, Makassar, South Sulawesi, Indonesia; Eijkman Institute for Molecular Biology, Jl. Diponegoro 69, Jakarta Pusat 10430, DKI Jakarta, Indonesia; Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia.
| |
Collapse
|
|
45
|
Liu J, Bi Y, Xu C, Liu L, Xu B, Chen T, Chen J, Pan M, Hu Y, Zhou YH. Kinetic Changes of Viremia and Viral Antigens of Hepatitis B Virus During and After Pregnancy. Medicine (Baltimore) 2015; 94:e2001. [PMID: 26559291 PMCID: PMC4912285 DOI: 10.1097/md.0000000000002001] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/23/2022] Open
Abstract
Whether pregnancy may influence the replication of hepatitis B virus (HBV) remains unknown. The authors aimed to clarify this issue by observing the kinetics of HBV deoxyribonucleic acid (DNA) and viral antigens in women during and after pregnancy. Total, 371 pregnant women with positive hepatitis B surface antigen (HBsAg) were enrolled. Serial sera collected during and after pregnancy were quantitatively measured for HBV DNA, HBsAg, and hepatitis B e antigen (HBeAg). Total, 34 HBeAg-positive women underwent alanine aminotransferase (ALT) elevation during or after pregnancy; levels of HBV DNA and HBsAg in them showed no obvious change between second trimester or delivery and 7 to 12 months postpartum (P > 0.05). The 337 others had normal alanine aminotransferase levels during pregnancy and postpartum. In 147 HBeAg-positive women with follow-up 7 to 12 months postpartum, the average levels of HBV DNA (>7.0 log10 IU/mL), HBsAg (>4.0 log10 IU/mL), and HBeAg (>3.0 log10 S/CO) were longitudinally constant during pregnancy and postpartum, respectively. In 173 women with follow-up 4.8 years postpartum, neither HBV DNA levels nor antigen titers showed significant difference between second trimester and 4.8 years postpartum, regardless of the HBeAg status. In addition, levels of HBV DNA and viral antigens in second trimester, around delivery, 6 to 8 weeks and 7 to 12 months postpartum showed no marked fluctuations, respectively. Serum levels of HBV DNA and viral antigens in HBsAg-positive women are highly constant during pregnancy and postpartum, regardless of the HBeAg status and alanine aminotransferase levels. This demonstrates that pregnancy has little influence on the HBV replication and antigen expression.
Collapse
Affiliation(s)
- Jingli Liu
- From the Department of Experimental Medicine (JL, YB, MP, Y-HZ), Jiangsu Key Laboratory for Molecular Medicine (JL, MP, YH, Y-HZ); Department of Obstetrics and Gynecology (JC, YH); Department of Infectious Diseases, Nanjing Drum Tower Hospital, Nanjing University Medical School, Jiangsu, China (Y-HZ); Zhenjiang Fourth People's Hospital (CX, TC); and Department of Obstetrics and Gynecology, Taixing People's Hospital, Jiangsu, China (LL, BX)
| | | | | | | | | | | | | | | | | | | |
Collapse
|
|
46
|
Ge GH, Ye Y, Zhou XB, Chen L, He C, Wen DF, Tan YW. Hepatitis B surface antigen levels of cessation of nucleos(t)ide analogs associated with virological relapse in hepatitis B surface antigen-negative chronic hepatitis B patients. World J Gastroenterol 2015; 21:8653-8659. [PMID: 26229407 PMCID: PMC4515846 DOI: 10.3748/wjg.v21.i28.8653] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/29/2015] [Revised: 03/26/2015] [Accepted: 05/04/2015] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the virological relapse rate in hepatitis B e antigen (HBeAg)-negative patients after antiviral therapy discontinuation and analyze the factors associated with virological relapse.
METHODS: Among patients diagnosed with chronic hepatitis B infection between May 2005 and July 2010, 204 were eligible for analysis. The Kaplan-Meier method and log-rank test were used to calculate the cumulative rate of relapse and compare cumulative relapse rates between groups. The Cox proportional hazards regression model was used to evaluate the predictive factor of virological relapse.
RESULTS: The 2 and 1 year cumulative risks of virological relapse after antiviral therapy discontinuation were 79.41% (162/204) and 43.82% (71/162), respectively. Multivariate analysis revealed that only post treatment hepatitis B surface antigen (HBsAg) level was associated with virological relapse (P = 0.011). The cumulative risk of virological relapse was higher in the patients with HBsAg levels ≥ 1500 IU/L than in those with HBsAg levels < 1500 IU/L (P = 0.0013). The area under the curve was 0.603 (P = 0.033). The cutoff HBsAg value for predicting virological relapse was 1443 IU/L.
CONCLUSION: We found that the virological relapse rate remained high after antiviral therapy discontinuation in the HBeAg-negative patients and that the post treatment HBsAg levels predicted virological relapse.
Collapse
|
|
47
|
Wang J, Liu J, Qi C, Yan T, Cao F, Jin L, He Y, Yang Y, Zhang S, Chen T, Zhao Y. Efficacy of tenofovir disoproxil fumarate to prevent vertical transmission in mothers with lamivudine-resistant HBV. Antivir Ther 2015. [PMID: 26215771 DOI: 10.3851/imp2981] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
BACKGROUND In China, women with chronic HBV infection and who are of childbearing age receive lamivudine at an early age. Thus, viral resistance becomes a challenge for intervention to prevent mother-to-infant transmission. We prospectively assessed the efficacy of tenofovir in pregnant women with lamivudine-resistant HBV. METHODS Chronic HBV-infected mothers resistant to lamivudine were enrolled. Tenofovir was administrated at gestation weeks 24 or 28. Virological and biochemical parameters were assessed. All infants received combined immunoprophylaxis and were followed for 1 year. RESULTS Of the 48 mothers enrolled, 21 started tenofovir therapy at gestation week 24 and 27 started at week 28. Tenofovir resulted in an HBV DNA decline of 5.23 ± 1.68 log10 IU/ml at delivery. The group starting therapy at week 24 exhibited a more rapid viral inhibition (P<0.001) and more significant HBV DNA load decline (5.89 ± 1.66 versus 4.72 ± 1.55; P=0.019) than the group starting at week 28. At delivery, all mothers had a viral titre <10(6) IU/ml, 76.2% from the week 24 starting group displayed virus <10(4) IU/ml, and 52.4% showed undetectable virus at delivery, much higher than the week 28 starting group (29.6%), although there was no statistically significant difference in viral levels at delivery between the two groups. Congenital abnormalities and neonatal growth were comparable to the normal population. No case of perinatal transmission was diagnosed. CONCLUSIONS This investigation clarifies the efficacy of tenofovir for reducing vertical transmission of HBV in mothers with lamivudine-resistant HBV and demonstrates that tenofovir is well-tolerated in the second and third trimesters.
Collapse
Affiliation(s)
- Jing Wang
- Department of Infectious Disease, the First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, China
| | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
48
|
Liu MH, Chen QY, Harrison TJ, Li GJ, Li H, Wang XY, Ju Y, Yang JY, Fang ZL. The correlation between serum HBsAg levels and viral loads depends upon wild-type and mutated HBV sequences rather than the HBeAg/anti-HBe status. J Med Virol 2015; 87:1351-60. [PMID: 25879734 PMCID: PMC4980755 DOI: 10.1002/jmv.24186] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/03/2015] [Indexed: 12/19/2022]
Abstract
Despite several studies regarding the correlation between serum HBsAg titers and viral loads, the association remains uncertain. Eighty‐nine individuals were selected randomly from a Chinese cohort of 2,258 subjects infected persistently with hepatitis B virus (HBV) for cross‐sectional and longitudinal analysis. Viral loads of mutant HBV are lower than those of wild type HBV. The serum HBsAg titers correlate positively with viral loads in both HBeAg positive and negative subjects (r = 0.449, P = 0.013; r = 0.300, P = 0.018, respectively). No correlation between serum HBsAg titer and viral loads was found in any of the four phases of chronic HBV infection. The serum HBsAg titers correlate positively with viral loads in the group with wild type sequences of the PreS/S, basal core promoter (BCP), and preC regions of HBV(r = 0.502, P = 0.040). However, the correlation was not seen in the group with mutations in these regions (r = 0.165, P = 0.257). The correlation between HBsAg titers and viral loads was seen in individuals with wild type PreS/S sequences but not in the subgroup with BCP double mutations or PreC stop mutation, although their sequences in the preS/S regions were wild type. All these findings were confirmed by the longitudinal analysis. In conclusion, the correlation between serum HBsAg levels and viral loads may not differ between HBeAg positive and negative individuals but may depend on wild‐type or mutated genomic sequences. Therefore, HBsAg quantitation may be used as a surrogate for viral loads in only wild‐type HBV infections. J. Med. Virol. 87:1351–1360, 2015. © 2015 The Authors. Journal of Medical Virology Published by Wiley Periodicals, Inc.
Collapse
Affiliation(s)
- Mo-Han Liu
- Department of Microbiology, School of Preclinical Medicine, Guangxi Medical University, Nanning, Guangxi, China.,Guangxi Zhuang Autonomous Region Center for Disease Prevention and Control, Nanning, Guangxi, China.,Guangxi Key Laboratory for the Prevention and Control of Viral Hepatitis, Nanning, Guangxi, China
| | - Qin-Yan Chen
- Guangxi Zhuang Autonomous Region Center for Disease Prevention and Control, Nanning, Guangxi, China.,Guangxi Key Laboratory for the Prevention and Control of Viral Hepatitis, Nanning, Guangxi, China
| | | | - Guo-Jian Li
- Department of Public Health of Guangxi Zhuang Autonomous Region, Nanning, Guangxi, China
| | - Hai Li
- Guangxi Zhuang Autonomous Region Center for Disease Prevention and Control, Nanning, Guangxi, China.,Guangxi Key Laboratory for the Prevention and Control of Viral Hepatitis, Nanning, Guangxi, China
| | - Xue-Yan Wang
- Guangxi Zhuang Autonomous Region Center for Disease Prevention and Control, Nanning, Guangxi, China.,Guangxi Key Laboratory for the Prevention and Control of Viral Hepatitis, Nanning, Guangxi, China
| | - Yu Ju
- Guangxi Zhuang Autonomous Region Center for Disease Prevention and Control, Nanning, Guangxi, China.,Guangxi Key Laboratory for the Prevention and Control of Viral Hepatitis, Nanning, Guangxi, China
| | - Jin-Ye Yang
- Guangxi Zhuang Autonomous Region Center for Disease Prevention and Control, Nanning, Guangxi, China.,Guangxi Key Laboratory for the Prevention and Control of Viral Hepatitis, Nanning, Guangxi, China
| | - Zhong-Liao Fang
- Guangxi Zhuang Autonomous Region Center for Disease Prevention and Control, Nanning, Guangxi, China.,Guangxi Key Laboratory for the Prevention and Control of Viral Hepatitis, Nanning, Guangxi, China
| |
Collapse
|
|
49
|
Fei QJ, Yang XD, Ni WH, Pan CS, Huang XF. Can hepatitis B virus DNA in semen be predicted by serum levels of hepatitis B virus DNA, HBeAg, and HBsAg in chronically infected men from infertile couples? Andrology 2015; 3:506-11. [PMID: 25873521 DOI: 10.1111/andr.12021] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2014] [Revised: 01/08/2015] [Accepted: 01/26/2015] [Indexed: 12/29/2022]
Abstract
Hepatitis B virus (HBV) in semen is important for father-to-child transmission of HBV and has adverse effects on sperm quality. However, risk factors associated with HBV in semen remain unclear. Serum HBV DNA and hepatitis B e antigen (HBeAg) levels may pose a risk on HBV in semen. This study aims to examine whether serum HBV DNA, HBeAg, and hepatitis B surface antigen (HBsAg) level were associated with HBV DNA in semen. 151 male patients chronically infected with HBV from infertile couples were included. Serum HBsAg and HBeAg were determined using an electrochemiluminescence immune assay (ECLIA). Serum and seminal plasma HBV DNA were detected by the QIAGEN Real-Time HBV DNA assay. Of 151 patients, 143 (94.7%) were serum HBV DNA-positive and 65 (43.0%) were seminal plasma HBV DNA-positive. Serum HBV DNA and HBeAg level of seminal plasma HBV DNA-positive patients were significantly higher (p < 0.001) as compared with those of seminal plasma HBV DNA-negative patients, HBsAg level of seminal plasma HBV DNA-positive patients was significantly lower (p < 0.001) compared with that of seminal plasma HBV DNA-negative patients. The best serum HBV DNA, HBeAg, and HBsAg value for discriminating between seminal plasma HBV DNA-positive and HBV DNA-negative patients were ≥6.9 log10 IU/mL (sensitivity 100.0%, specificity 90.7%), >14.8 S/CO (sensitivity 96.9%, specificity 81.5%), and <1791.5 S/CO (sensitivity 81.5%, specificity 81.2%), respectively. The combination of serum HBV DNA and HBeAg had high diagnostic sensitivity (100.0%) and specificity (95.4%) for the presence of HBV DNA in semen. As such, these serum markers especially the combination of HBV DNA and HBeAg are useful predictors of the presence of HBV DNA in semen in HBV chronically infected men from infertile couples.
Collapse
Affiliation(s)
- Q J Fei
- Reproductive Medicine Center, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - X D Yang
- Department of Infectious Disease, Yuying Children's Hospital Affiliated to Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - W H Ni
- Reproductive Medicine Center, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - C S Pan
- Reproductive Medicine Center, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - X F Huang
- Reproductive Medicine Center, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
| |
Collapse
|
|
50
|
Tran TT, Gordon SC, Fung S, Dinh P, Yee L, Martins EB, Buti M, Marcellin P. Hepatitis B e antigen status and hepatitis B DNA levels in women of childbearing age with chronic hepatitis B infection screening for clinical trials. PLoS One 2015; 10:e0121632. [PMID: 25789483 PMCID: PMC4366373 DOI: 10.1371/journal.pone.0121632] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2014] [Accepted: 02/11/2015] [Indexed: 01/05/2023] Open
Abstract
BACKGROUND Perinatal or mother-to-child transmission of hepatitis B virus (HBV) results in a high frequency of chronic infection. Risk of mother-to-child transmission is associated with maternal viral factors including hepatitis B e antigen (HBeAg) positivity and viral load. AIM To investigate associations between age, HBeAg status, HBV DNA levels and genotype in female patients screened for inclusion into two contemporary, randomized HBV trials. METHODS Retrospective analyses focused on differences between women of childbearing age (≤44 years) and older women. Female patients (N = 355; 18-69 years) were included in the analysis: 41.7% of patients were Asian. In total, 44.4% were HBeAg-positive. RESULTS Significantly more women aged ≤44 years were HBeAg-positive compared to women ≥45 years (57.2% versus 27.5%, respectively, p<0.0001), this proportion declined with increasing age. Younger women were significantly more likely to have high HBV viral load (HBV DNA>108 copies mL: ≤44 years 46.0% vs ≥45 years 25.5%, respectively; p<0.0001), and this declined with increasing age. HBeAg positivity was slightly higher in Asian women, associated with a higher proportion of HBV genotypes B and C in this population. There was no obvious relationship between genotype and viral load. CONCLUSIONS Women of childbearing age with CHB are more likely to have high HBV viral load and HBeAg positivity than older women; this likelihood decreases with age. Maternal serological and virological status should therefore be established early in pregnancy, taking into account age and genotype, and a risk-reducing strategy implemented in any patient who is HBeAg positive and has a high viral load.
Collapse
Affiliation(s)
- Tram T. Tran
- Liver Disease and Transplant Center, Cedars-Sinai Medical Center, Los Angeles, California, United States of America
- * E-mail:
| | - Stuart C. Gordon
- Division of Hepatology, Henry Ford Hospital, Detroit, Michigan, United States of America
| | - Scott Fung
- Department of Medicine, University of Toronto, Toronto, Canada
| | - Phillip Dinh
- Gilead Sciences, Foster City, California, United States of America
| | - Leland Yee
- Gilead Sciences, Foster City, California, United States of America
| | | | - Maria Buti
- Department of Hepatology, Hospital General Universitario Valle Hebron and Ciberehd del Instituto Carlos III, Barcelona, Spain
| | | |
Collapse
|