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Han G, Zhou G, Sun T, Luo X, Xu J, Chen C, Xu W, Jiang S, Wang C. Tenofovir alafenamide in blocking mother-to-child transmission of hepatitis B virus: a multi-center, prospective study. J Matern Fetal Neonatal Med 2022; 35:10551-10558. [PMID: 36253882 DOI: 10.1080/14767058.2022.2134771] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2022] [Revised: 09/12/2022] [Accepted: 10/06/2022] [Indexed: 01/20/2023]
Abstract
BACKGROUND Data of tenofovir alafenamide (TAF) in preventing mother-to-child transmission (MTCT) of hepatitis B virus (HBV) are limited. This study aimed to evaluate the effectiveness and safety of TAF for preventing MTCT. METHODS Pregnant women with chronic HBV infection, positive for HBeAg and high-level HBV DNA, received oral TAF from gestational weeks 24-28 until postpartum week 4. All infants received HBV immunoprophylaxis. All mothers and infants were followed up until postpartum seven month. The primary outcome was the rate of MTCT at seven month. RESULTS Eighty-nine mothers delivered and 91 infants were born. All were followed up to postpartum seven month. TAF was initiated at a mean gestational age of 25.0 (±1.0) weeks with the mean treatment duration of 14.3 (±1.2) weeks before delivery; 92.1% (82/89) mothers discontinued TAF, the median [IQR] time was 5.9 [4.7] weeks postpartum. The HBsAg positive rate was 0% at seven months in 91 infants, no growth retardation and congenital defects. All mothers were tolerated during TAF treatment. At delivery, 82.02% (73/89) mothers achieved HBV DNA < 200,000 IU/ml, 21.35% (19/89) achieved HBV DNA < 500 IU/ml. No significant changes on the mean (±SD) serum phosphate between baseline (1.20 ± 0.10 mmol/L) and at delivery (1.21 ± 0.13 mmol/L, p > .05). Serum creatinine at delivery (52.23 ± 8.50 µmol/L) was higher than baseline (45.97 ± 5.60 µmol/L, p < .05), but within normal range. Nine of 82 mothers stopped TAF treatment after delivery had mild ALT elevation. CONCLUSION TAF therapy initiated during the second trimester was effective in preventing MTCT with no safety concerns for mothers and infants (ClinicalTrials.gov number, NCT04065230).
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Affiliation(s)
- Guorong Han
- Department of Obstetrics and Gynecology, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing, China
| | - Guanlun Zhou
- Department of Obstetrics and Gynecology, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing, China
| | - Tong Sun
- Department of Hepatology, The Fifth People's Hospital of Wuxi, Wuxi, China
| | - Xiucui Luo
- Department of Obstetrics and Gynecology, The Maternal and Child Health Hospital of Lianyungang, Lianyungang, China
| | - Jinxia Xu
- Department of Obstetrics and Gynecology, The Maternal and Child Health Hospital of Huai'an, Huai'an, China
| | - Chao Chen
- Department of Obstetrics and Gynecology, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing, China
| | - Wen Xu
- Department of Obstetrics and Gynecology, The Maternal and Child Health Hospital of Lianyungang, Lianyungang, China
| | - Su'e Jiang
- Department of Obstetrics and Gynecology, The Maternal and Child Health Hospital of Huai'an, Huai'an, China
| | - Chenxu Wang
- Department of Obstetrics and Gynecology, The Second Hospital of Nanjing, Medical School of Nanjing University, Nanjing, China
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Antiviral Therapy for Prevention of Perinatal Hepatitis B Virus Transmission Reduces the Incidence of Postpartum Hepatitis Flare. BIOMED RESEARCH INTERNATIONAL 2022; 2022:7046955. [PMID: 35860799 PMCID: PMC9293540 DOI: 10.1155/2022/7046955] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/03/2022] [Revised: 06/11/2022] [Accepted: 06/20/2022] [Indexed: 11/23/2022]
Abstract
Background: Currently, there are few studies on the effect of prophylactic anti-hepatitis B virus (HBV) therapy (AVT) for mother-to-child transmission during pregnancy on postpartum hepatitis flare (PHF) and the risk factors for postpartum hepatitis flare in women with chronic hepatitis B infection. Aim: To analyze the effect of AVT on the postpartum hepatitis flare and risk factors related to postpartum hepatitis flare. Methods: This study retrospectively enrolled hepatitis B surface antigen (HBsAg)-positive and hepatitis B e antigen (HBeAg)-positive women with HBV DNA ≥ 106 IU/mL. Six hundred fourteen pregnant women were included: 444 in the anti-HBV therapy group (T-G) and 170 in the control group (C-G). To analyze the risk factors, women with alanine aminotransferase (ALT) flare (ALT > 40 U/L) were assigned to the PHF group (PHF-G, n = 355), and all the others were assigned to a non-PHF group (NPHF-G, n = 259). Results: At 6 weeks postpartum, ALT and AST levels were higher, and ALB levels were lower in the C-G than those in T-G (P < 0.05). Also, ALT (at baseline, pregnancy 32nd and 36th, intrapartum), AST (at pregnancy 32nd and 36th week, and intrapartum), HBcAb (at baseline, intrapartum), and HBV DNA (at intrapartum) of PHF-G were significantly higher than those of NPHF-G (P < 0.05). Multivariate analysis showed that ALT (OR = 1.067, P < 0.001) and HBcAb (OR = 1.213, P ≤ 0.001) in pregnant women were risk factors for PHF. The prophylactic anti-HBV for the prevention of perinatal HBV transmission (OR = 0.357, P < 0.001) was the protective factor for PHF. Conclusion: Pregnant women with prophylactic anti-HBV during the third trimester of pregnancy had a lower incidence of postpartum hepatitis flare, especially a lower risk of serious hepatitis flare. ALT and HBcAb in pregnant women were risk factors for PHF. Women infected with HBV should be closely monitored ALT during pregnancy and postpartum.
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Zhang B, Yu L, Cheng M, Zhang Q, Wu J, Yang J, Liu Q, Lu S, Zhao X, Deng K, Liu Y, Wang J, Zhao P. Hepatitis B virus genotype is an independent prognostic factor of telbivudine and tenofovir treatment in hepatitis B surface antigen-positive pregnant women. Food Sci Nutr 2022; 10:3-11. [PMID: 35035905 PMCID: PMC8751444 DOI: 10.1002/fsn3.2619] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2021] [Revised: 07/14/2021] [Accepted: 07/21/2021] [Indexed: 11/06/2022] Open
Abstract
To investigate whether HBV genotype influences the effect of tenofovir and telbivudine on HBV DNA and RNA levels in HBsAg-positive pregnant women. This was a retrospective study of 74 HBsAg-positive pregnant women in Guizhou of China. All patients were treated with telbivudine or tenofovir from 12 weeks of pregnancy and HBV infection to the date of delivery. Blood samples were collected at 12-24, 28-32, and 36-40 weeks of pregnancy for the measurement of genotype, HBsAg, hepatitis B e antigen (HBeAg), HBV DNA, HBV RNA, and liver function, including alanine transaminase, aspartate transaminase, total bilirubin, total bile acids, cholinesterase, alkaline phosphatase (ALP), and gamma-glutamyl transferase. All women with HBsAg were followed up. The HBV genotype was B in 64.9% and C in 35.1%. There were 37 patients of telbivudine and tenofovir group respectively. The telbivudine and tenofovir groups showed no differences in demographic and clinical characteristics, including liver function tests, HBsAg, HBeAg, log10(HBV DNA), and log10(HBV RNA). Compared with baseline (12-24 weeks), telbivudine group showed a significant increase in ALP and significant reductions in HBsAg, HBeAg, log10(HBV DNA), and log10(HBV RNA) at 36-40 weeks (p < .05). Tenofovir group exhibited a significant increase in ALP and significant reductions in HBeAg, log10(HBV DNA), and log10(HBV RNA) at 36-40 weeks, compared with baseline (p < .05). HBV genotype (B vs. C) was independently associated with HBV DNA change after therapy (p = .005). In telbivudine group, log10 (HBV DNA) increased from 3.38 (2.00-7.30) to 7.43 (4.68-8.70). In tenofovir group, log10 (HBV DNA) decreased from 7.52 (3.32-8.70) to 2.98 (2.00-5.01). HBV genotype was independently associated with HBV DNA change response to telbivudine or tenofovir in pregnant women with hepatitis B. These findings might be helpful for risk assessment regarding vertical transmission of HBV in HBeAg-positive mothers treated with nucleos(t)ide analogues.
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Affiliation(s)
- Baofang Zhang
- The Affliated HospitalGuizhou Medical UniversityGuiyang, GuizhouChina
| | - Lei Yu
- Prenatal Diagnosis CenterGuizhou Medical UniversityGuiyang, GuizhouChina
| | - Mingliang Cheng
- The Affliated HospitalGuizhou Medical UniversityGuiyang, GuizhouChina
| | - Quan Zhang
- The Affliated HospitalGuizhou Medical UniversityGuiyang, GuizhouChina
| | - Jun Wu
- The Affliated HospitalGuizhou Medical UniversityGuiyang, GuizhouChina
| | - Jing Yang
- The Affliated HospitalGuizhou Medical UniversityGuiyang, GuizhouChina
| | - Qin Liu
- The Affliated HospitalGuizhou Medical UniversityGuiyang, GuizhouChina
| | - Shuang Lu
- The Affliated HospitalGuizhou Medical UniversityGuiyang, GuizhouChina
| | - Xueke Zhao
- The Affliated HospitalGuizhou Medical UniversityGuiyang, GuizhouChina
| | - KaiSheng Deng
- The Affliated HospitalGuizhou Medical UniversityGuiyang, GuizhouChina
| | - Yongmei Liu
- LaboratoryGuizhou Medical UniversityGuiyang, GuizhouChina
| | - Jun Wang
- Clinical Research CenterGuizhou Medical UniversityGuiyang, GuizhouChina
| | - Peiling Zhao
- LaboratoryGuizhou Medical UniversityGuiyang, GuizhouChina
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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.
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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
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Schultheiss HP, Bock T, Pietsch H, Aleshcheva G, Baumeier C, Fruhwald F, Escher F. Nucleoside Analogue Reverse Transcriptase Inhibitors Improve Clinical Outcome in Transcriptional Active Human Parvovirus B19-Positive Patients. J Clin Med 2021; 10:1928. [PMID: 33946917 PMCID: PMC8125167 DOI: 10.3390/jcm10091928] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2021] [Revised: 04/24/2021] [Accepted: 04/25/2021] [Indexed: 01/01/2023] Open
Abstract
Human parvovirus B19 (B19V) is the predominant cardiotropic virus associated with dilated inflammatory cardiomyopathy (DCMi). Transcriptionally active cardiotropic B19V infection is clinically relevant and triggers adverse long-term mortality. During the study; we evaluated whether antiviral treatment with the nucleoside analogue telbivudine (LTD) is effective in suppressing transcriptional active B19V in endomyocardial biopsies (EMBs) of B19V positive patients and improving clinical outcomes. Seventeen B19V-positive patients (13 male; mean age 45.7 ± 13.9 years; mean left ventricular ejection fraction (LVEF) 37.7 ± 13.5%) with positive B19V DNA and transcriptional activity (B19V mRNA) in EMBs were treated with 600 mg/d LTD over a period of six months. Patients underwent EMBs before and after termination of the LTD treatment. B19V RNA copy numbers remained unchanged in 3/17 patients (non-responder) and declined or disappeared completely in the remaining 14/17 patients (responder) (p ≤ 0.0001). Notably; LVEF improvement was more significant in patients who reduced or lost B19V RNA (responder; p = 0.02) in contrast to non-responders (p = 0.7). In parallel; responder patients displayed statistically significant improvement in quality of life (QoL) questionnaires (p = 0.03) and dyspnea on exertion (p = 0.0006), reflecting an improvement in New York Heart Association (NYHA) Classification (p = 0.001). Our findings demonstrated for the first time that suppression of B19V transcriptional activity by LTD treatment improved hemodynamic and clinical outcome significantly. Thus; the present study substantiates the clinical relevance of detecting B19V transcriptional activity of the myocardium.
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Affiliation(s)
- Heinz-Peter Schultheiss
- Institute of Cardiac Diagnostics and Therapy, 12203 Berlin, Germany; (T.B.); (H.P.); (G.A.); (C.B.); (F.E.)
- Department of Cardiology, Campus Benjamin Franklin, Charité-Universitätsmedizin Berlin, 12200 Berlin, Germany
| | - Thomas Bock
- Institute of Cardiac Diagnostics and Therapy, 12203 Berlin, Germany; (T.B.); (H.P.); (G.A.); (C.B.); (F.E.)
- Institute of Tropical Medicine, University of Tübingen, 72074 Tübingen, Germany
| | - Heiko Pietsch
- Institute of Cardiac Diagnostics and Therapy, 12203 Berlin, Germany; (T.B.); (H.P.); (G.A.); (C.B.); (F.E.)
- Department of Internal Medicine and Cardiology, Campus Virchow Klinikum, Charité-Universitätsmedizin Berlin, 13353 Berlin, Germany
- DZHK (German Centre for Cardiovascular Research), Berlin, Germany
| | - Ganna Aleshcheva
- Institute of Cardiac Diagnostics and Therapy, 12203 Berlin, Germany; (T.B.); (H.P.); (G.A.); (C.B.); (F.E.)
| | - Christian Baumeier
- Institute of Cardiac Diagnostics and Therapy, 12203 Berlin, Germany; (T.B.); (H.P.); (G.A.); (C.B.); (F.E.)
| | | | - Felicitas Escher
- Institute of Cardiac Diagnostics and Therapy, 12203 Berlin, Germany; (T.B.); (H.P.); (G.A.); (C.B.); (F.E.)
- Department of Internal Medicine and Cardiology, Campus Virchow Klinikum, Charité-Universitätsmedizin Berlin, 13353 Berlin, Germany
- DZHK (German Centre for Cardiovascular Research), Berlin, Germany
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Liu J, Chen T, Chen Y, Ren H, Wang G, Zhang W, Zhao Y. 2019 Chinese Clinical Practice Guidelines for the Prevention of Mother-to-child Transmission of Hepatitis B Virus. J Clin Transl Hepatol 2020; 8:397-406. [PMID: 33447523 PMCID: PMC7782118 DOI: 10.14218/jcth.2020.00070] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/22/2020] [Revised: 08/18/2020] [Accepted: 09/08/2020] [Indexed: 12/13/2022] Open
Abstract
To develop the evidence-based guidelines for managing mother-to-child transmission of hepatitis B virus in China, a multidisciplinary guideline development group was established. Clinical questions were identified from two rounds of surveys on the concerns of first-line clinicians. We conducted a comprehensive search and review of the literature. A grading of recommendations' assessment, development, and evaluation system was adopted to rate the quality of evidence and the strength of recommendations. Recommendations were formulated based on the evidence, overall balance of benefits and harms (at individual and population levels), patient/health worker values and preferences, resources available, cost-effectiveness, and feasibility. Eventually, recommendations related to 13 main clinical concerns were developed, covering diagnostic criteria, treatment indications, antiviral therapy choice, timing to initiate and discontinue treatment, immunoprophylaxis strategy at birth, and how to deal with special situations, such as unintended pregnancy, assisted reproduction, and breastfeeding. The guidelines are intended to serve as guidance for clinicians and patients, to optimize the management of majority of pregnant women who are positive for hepatitis B surface antigen. Guideline registration: International Practice Guide Registration Platform (IPGRP-2018CN040).
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Affiliation(s)
- Jinfeng Liu
- The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, China
- Shaanxi Clinical Research Center of Infectious Diseases, Xi’an, Shaanxi, China
| | - Tianyan Chen
- The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, China
- Shaanxi Clinical Research Center of Infectious Diseases, Xi’an, Shaanxi, China
| | - Yaolong Chen
- Evidence-Based Medicine Center, Basic Medical Sciences, Lanzhou University, Lanzhou, Gansu, China
- WHO Collaborating Centre for Guideline Implementation and Knowledge Translation, Lanzhou, Gansu, China
| | - Hong Ren
- Department of Infectious Diseases, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Guiqiang Wang
- Hepatology Center, Department of Infectious Diseases, Peking University First Hospital, Beijing, China
| | - Wenhong Zhang
- Department of Infectious Diseases, Huashan Hospital Affiliated to Fudan University, Shanghai, China
| | - Yingren Zhao
- The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, China
- Shaanxi Clinical Research Center of Infectious Diseases, Xi’an, Shaanxi, China
| | - Society of Infectious Diseases and Chinese Medical Association
- The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, China
- Shaanxi Clinical Research Center of Infectious Diseases, Xi’an, Shaanxi, China
- Evidence-Based Medicine Center, Basic Medical Sciences, Lanzhou University, Lanzhou, Gansu, China
- WHO Collaborating Centre for Guideline Implementation and Knowledge Translation, Lanzhou, Gansu, China
- Department of Infectious Diseases, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
- Hepatology Center, Department of Infectious Diseases, Peking University First Hospital, Beijing, China
- Department of Infectious Diseases, Huashan Hospital Affiliated to Fudan University, Shanghai, China
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Evidence for Use of Tenofovir in Pregnancy to Prevent Perinatal Transmission of Hepatitis B Infection. Clin Obstet Gynecol 2020; 62:835-845. [PMID: 30921004 DOI: 10.1097/grf.0000000000000438] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
Perinatal transmission of hepatitis B virus continues to be a serious global public health concern. Transmission failures are related to high maternal viremia. Several antiviral therapies reduce maternal viremia around the time of delivery and decrease maternal-to-child-transmission. This chapter is a review of current studies that, ultimately, have provided strong evidence for the efficacy and safety of 3 antiviral drugs in pregnancy-lamivudine, telbivudine and tenofovir. The latter drug is the particular focus of this chapter which will show that tenofovir is the preferred antiviral therapy in pregnant women because of its potency, safety profile, and low risk of resistance.
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Posuwan N, Wanlapakorn N, Sintusek P, Wasitthankasem R, Poovorawan K, Vongpunsawad S, Poovorawan Y. Towards the elimination of viral hepatitis in Thailand by the year 2030. J Virus Erad 2020; 6:100003. [PMID: 33251021 PMCID: PMC7646674 DOI: 10.1016/j.jve.2020.100003] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2019] [Revised: 01/12/2020] [Accepted: 06/23/2020] [Indexed: 12/19/2022] Open
Abstract
Viral hepatitis is a global problem with mortality comparable to HIV, tuberculosis and malaria. The WHO aims to eliminate hepatitis B (HBV) and hepatitis C (HCV) by 2030. Improved socioeconomic status of developing countries such as Thailand has reduced the incidence and morbidity associated with hepatitis A. Since the beginning of hepatitis B vaccination in all Thai newborns in 1992, at least 95% of one-year-olds are currently receiving 3-4 hepatitis B doses. The second vaccination of newborns of carrier mothers at 1 month of age has contributed to an effective reduction in mother-to-child transmission. Universal vaccination, blood donation screening, and decreasing needle sharing have reduced hepatitis B infection. Under the test and treat model, cost-effective screening at the point-of-care (health center or village hospital) is recommended for adults >30 years-old. Following referral to a tertiary healthcare center for a treatment plan in developing disease management plan, its implementation by trained healthcare professionals is preferably administered at the point-of-care. Hepatitis C prevalence is also decreasing as a result of blood-borne pathogen awareness. Current hepatitis C infection is highest for adults >35 years who were born prior to 1983, with screening is recommend once in their lifetime. Treatment strategy recommendation follows that of hepatitis B. The availability of direct antiviral agents with high cure rates is expected to contribute to the reduction in hepatitis C transmission and mortality as set forth by the WHO policy. Thus, ensuring the successful planning of hepatitis elimination in Thailand requires pilot regional assessment prior to national implementation.
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Affiliation(s)
- Nawarat Posuwan
- Center of Excellence in Clinical Virology, Faculty of Medicine, Chulalongkorn University Bangkok, Thailand
| | - Nasamon Wanlapakorn
- Center of Excellence in Clinical Virology, Faculty of Medicine, Chulalongkorn University Bangkok, Thailand
- Division of Academic Affairs, Faculty of Medicine, Chulalongkorn University Bangkok, Thailand
| | - Palittiya Sintusek
- STAR (Special Task Force for Activating Research), Pediatric Gastroenterology and Hepatology, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University Bangkok, Thailand
| | - Rujipat Wasitthankasem
- National Biobank of Thailand, National Science and Technology Development Agency, Thailand Science Park, Pathum Thani, Thailand
| | - Kittiyod Poovorawan
- Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
| | - Sompong Vongpunsawad
- Center of Excellence in Clinical Virology, Faculty of Medicine, Chulalongkorn University Bangkok, Thailand
| | - Yong Poovorawan
- Center of Excellence in Clinical Virology, Faculty of Medicine, Chulalongkorn University Bangkok, Thailand
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Efficacy and safety of antiviral prophylaxis during pregnancy to prevent mother-to-child transmission of hepatitis B virus: a systematic review and meta-analysis. THE LANCET. INFECTIOUS DISEASES 2020; 21:70-84. [PMID: 32805200 DOI: 10.1016/s1473-3099(20)30586-7] [Citation(s) in RCA: 116] [Impact Index Per Article: 23.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/11/2020] [Revised: 06/10/2020] [Accepted: 07/10/2020] [Indexed: 12/20/2022]
Abstract
BACKGROUND To eliminate mother-to-child transmission (MTCT) of hepatitis B virus (HBV), peripartum antiviral prophylaxis might be required for pregnant women infected with HBV who have a high risk of MTCT despite infant immunoprophylaxis. We aimed to determine the efficacy and safety of peripartum antiviral prophylaxis to inform the 2020 WHO guidelines. METHODS In this systematic review and meta-analysis, we searched PubMed, Embase, Scopus, CENTRAL, CNKI, and Wanfang for randomised controlled trials and non-randomised studies of peripartum antiviral prophylaxis versus placebo or no prophylaxis, with no language restriction, published from database inception until March 28, 2019. We used search terms covering HBV, antiviral therapy, and pregnancy. We included studies that enrolled pregnant women with chronic infection with HBV who received antiviral prophylaxis anytime during pregnancy; that included any of the following antivirals: adefovir, emtricitabine, entecavir, lamivudine, telbivudine, tenofovir alafenamide fumarate, and tenofovir disoproxil fumarate; and that reported the following outcomes: MTCT, indicated by infant HBsAg positivity or HBV DNA positivity, or both, at age 6-12 months, and any infant or maternal adverse events. Two reviewers independently extracted data. Our primary endpoint was MTCT based on infant HBsAg positivity. We assessed pooled odds ratios (ORs) of the efficacy of peripartum antiviral prophylaxis to reduce the risk of MTCT. We assessed safety of prophylaxis by pooling risk differences. The protocol for the systematic review was pre-registered in PROSPERO, CRD42019134614. FINDINGS Of 7463 articles identified, 595 articles were eligible for full-text review and 129 studies (in 157 articles) were included. The following antivirals were assessed in the meta-analysis: tenofovir disoproxil fumarate 300 mg (19 studies, with 1092 mothers and 1072 infants), lamivudine 100-150 mg (40 studies, with 2080 mothers and 2007 infants), and telbivudine 600 mg (83 studies, with 6036 mothers and 5971 infants). The pooled ORs for randomised controlled trials were similar, at 0·10 (95% CI 0·03-0·35) for tenofovir disoproxil fumarate, 0·16 (0·10-0·26) for lamivudine, and 0·14 (0·09-0·21) for telbivudine. The pooled ORs in non-randomised studies were 0·17 (0·10-0·29) for tenofovir disoproxil fumarate, 0·17 (0·12-0·24) for lamivudine, and 0·09 (0·06-0·12) for telbivudine. We found no increased risk of any infant or maternal safety outcomes after peripartum antiviral prophylaxis. INTERPRETATION Peripartum antiviral prophylaxis is highly effective at reducing the risk of HBV MTCT. Our findings support the 2020 WHO recommendation of administering antivirals during pregnancy, specifically tenofovir disoproxil fumarate, for the prevention of HBV MTCT. FUNDING World Health Organization.
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Ren C, Wang L, Sun W, Ma L, Dong Z, Hao A, Zhou L, Li F, Ma W. Efficacy and safety of telbivudine treatment for the prevention of HBV perinatal transmission. Medicine (Baltimore) 2020; 99:e20583. [PMID: 32541488 PMCID: PMC7302680 DOI: 10.1097/md.0000000000020583] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/30/2022] Open
Abstract
To observe the efficacy of telbivudine in chronic hepatitis B (CHB) women with high viral load during pregnancy and the long-term effects on intelligence, growth, and development of the newborns.A total of 87 patients were included. Forty-two patients received telbivudine orally 600 mg per day and treatment initiated from 12 weeks after gestation until the 12th postpartum week. Forty-five patients were untreated according to principle of informed consent. All infants received injection of hepatitis B immune globulin (HBIG; 200 IU) and were vaccinated with recombinant HBV vaccine. Wechsler preschool intelligence scale was used to assess mental and neuropsychological developments of these children till they were 6 years old. Data including serum HBV DNA viral load, Apgar score, and scores of Wechsler preschool intelligence scale were analyzed and compared.Levels of both serum HBV DNA and ALT in patients who received telbivudine were significantly decreased at the 12th week after delivery, compared with baseline levels (P < .01). No significant changes were observed in patients not receiving telbivudine (P > .05). Serum HBV DNA and ALT levels at the 12th week after delivery in the telbivudine group were significantly lower than those of patients without telbivudine (P < .01). The serum HBsAg-positive rate in neonates 7 months of age was 0%, which was significantly lower than that in control group (11.11%) (P < .05). No statistical differences were observed between the 2 groups regarding maternal cesarean section rate, adverse pregnancy rate, postpartum bleeding rate, neonatal body mass, Apgar score, neonatal malformation incidence, or intelligence development of newborn.Telbivudine is effective to reduce the viral load in CHB mothers with high viral load and could lower the perinatal transmission rate. Both mental and physical development in neonates with exposure to telbivudine during perinatal period were similar to those without telbivudine exposure.
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Affiliation(s)
| | - Lili Wang
- Fifth Ward of Internal Medicine, Sixth People's Hospital
| | - Weihui Sun
- Hepatology Department, Qingdao Chengyang People's Hospital
| | - Lei Ma
- Hepatology Department, Qingdao Chengyang People's Hospital
| | - Zhi Dong
- Hepatology Department, Qingdao Chengyang People's Hospital
| | - Anhua Hao
- Hepatology Department, Qingdao Chengyang People's Hospital
| | - Lin Zhou
- Hepatology Department, Qingdao Chengyang People's Hospital
| | - Fengzhu Li
- Hepatology Department, Qingdao Chengyang People's Hospital
| | - Wenjie Ma
- First-aid Station, Sixth People's Hospital, Qingdao city, Shandong Province, China
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11
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Hu Y, Yu H. Prevention strategies of mother-to-child transmission of hepatitis B virus (HBV) infection. Pediatr Investig 2020; 4:133-137. [PMID: 32851357 PMCID: PMC7331440 DOI: 10.1002/ped4.12205] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2020] [Accepted: 06/09/2020] [Indexed: 02/07/2023] Open
Abstract
Chronic hepatitis B virus (HBV) infection caused by mother-to-child transmission (MTCT, also known as vertical transmission) during the perinatal period is a major public health problem worldwide. Despite the availability of the combined active-passive immunization with a hepatitis B vaccine and hepatitis B immunoglobulin after birth, about 9% of newborns are still infected with HBV, especially those born to hepatitis B e antigen (HBeAg)-positive mothers. Currently, the management of HBV infection during pregnancy remains controversial. This article briefly reviews the recent advances in the epidemiology of HBV, immunization against it, and management strategies in the third trimester.
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Affiliation(s)
- Yao Hu
- Department of Infectious DiseasesChildren’s Hospital of Fudan UniversityShanghaiChina
| | - Hui Yu
- Department of Infectious DiseasesChildren’s Hospital of Fudan UniversityShanghaiChina
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12
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Wu Y, Liu J, Feng Y, Fu S, Ji F, Ge L, Yao N, Luo X, Zhao Y, Chen Y, Yang Y, Chen T. Efficacy and safety of antiviral therapy for HBV in different trimesters of pregnancy: systematic review and network meta-analysis. Hepatol Int 2020; 14:180-189. [PMID: 32193814 PMCID: PMC7136311 DOI: 10.1007/s12072-020-10026-0] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/25/2019] [Accepted: 02/21/2020] [Indexed: 02/07/2023]
Abstract
BACKGROUND Several antiviral agents licenced for blocking mother-to-child transmission (MTCT) of HBV, but their relative efficacy beginning from different trimesters has scarce been evaluated. We aimed to conduct a network meta-analysis to statistically differ the efficacy and safety of each antiviral agents initiating on different timings in preventing mother-to-infant transmission of HBV. METHODS Studies were included from PubMed, EMBASE, Web of Science, and Cochrane databases through July 1, 2019. Eligible studies recruited randomized controlled trials and nonrandomized studies reporting about infant or/and maternal efficacy and safety outcomes and were screened by two investigators independently. Extracted data were analyzed by pair-wised and network meta-analysis, respectively. RESULTS 3 Randomized and 32 nonrandomized studies enrolling 6738 pregnant female were included. Using network analysis, any antiviral agent interrupted HBV vertical transmission much more effectively than placebo. No agent showed significant efficacy different from others, but a strong trend toward significance was found in telbivudine and tenofovir, of which had the highest probability of being ranked the first- or second-best treatment for reducing MTCT of HBV. The treatment applied in the first and second trimester had a similar efficacy in preventing MTCT. Compared with the initiation during the third trimester, lower rate of MTCT was revealed when antiviral therapy was administrated before third trimester, (RR = 0.045, 95% CI 0.0053 to 0.20); a similar effect at delivery on suppressing maternal HBV DNA level and converting serum HBeAg were achieved if the timing of antiviral treatment started prior, but an obvious improvement of normalizing ALT flare was calculated out; no statistically differences among maternal and fetal safety outcomes were found if mothers received antiviral agents before pregnant 28 weeks. CONCLUSION This network meta-analysis recommended the earlier use of telbivudine or tenofovir, tends to be better to prevent MTCT of HBV in pregnancy with no increased adverse maternal or fetal outcomes.
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Affiliation(s)
- Yuchao Wu
- Department of Infection Disease and Hepatopathy, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, Shaanxi, China
| | - Jinfeng Liu
- Department of Infection Disease and Hepatopathy, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, Shaanxi, China
| | - Yali Feng
- Department of Infection Disease and Hepatopathy, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, Shaanxi, China
| | - Shan Fu
- Department of Infection Disease and Hepatopathy, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, Shaanxi, China
| | - Fanpu Ji
- Department of Infection Disease and Hepatopathy, Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China
| | - Long Ge
- Evidence-Based Medicine Center, Basic Medical Sciences, Lanzhou University, Lanzhou, China
- WHO Collaborating Centre for Guideline Implementation and Knowledge Translation, Lanzhou, China
| | - Naijuan Yao
- Department of Infection Disease and Hepatopathy, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, Shaanxi, China
| | - Xufei Luo
- Evidence-Based Medicine Center, Basic Medical Sciences, Lanzhou University, Lanzhou, China
- WHO Collaborating Centre for Guideline Implementation and Knowledge Translation, Lanzhou, China
| | - Yingren Zhao
- Department of Infection Disease and Hepatopathy, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, Shaanxi, China
| | - Yaolong Chen
- Evidence-Based Medicine Center, Basic Medical Sciences, Lanzhou University, Lanzhou, China.
- WHO Collaborating Centre for Guideline Implementation and Knowledge Translation, Lanzhou, China.
| | - Yuan Yang
- Department of Infection Disease and Hepatopathy, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, Shaanxi, China.
| | - Tianyan Chen
- Department of Infection Disease and Hepatopathy, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, Shaanxi, China.
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13
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Tao Y, Wu D, Zhou L, Chen E, Liu C, Tang X, Jiang W, Han N, Li H, Tang H. Present and Future Therapies for Chronic Hepatitis B. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2019; 1179:137-186. [PMID: 31741336 DOI: 10.1007/978-981-13-9151-4_6] [Citation(s) in RCA: 34] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Chronic hepatitis B (CHB) remains the leading cause of liver-related morbidity and mortality across the world. If left untreated, approximately one-third of these patients will progress to severe end-stage liver diseases including liver failure, cirrhosis, and hepatocellular carcinoma (HCC). High level of serum HBV DNA is strongly associated with the development of liver failure, cirrhosis, and HCC. Therefore, antiviral therapy is crucial for the clinical management of CHB. Current antiviral drugs including nucleoside/nucleotide analogues (NAs) and interferon-α (IFN-α) can suppress HBV replication and reduce the progression of liver disease, thus improving the long-term outcomes of CHB patients. This chapter will discuss the standard and optimization antiviral therapies in treatment-naïve and treatment-experienced patients, as well as in the special populations. The up-to-date advances in the development of new anti-HBV agents will be also discussed. With the combination of the current antiviral drugs and the newly developed antiviral agents targeting the different steps of the viral life cycle or the newly developed agents modulating the host immune responses, the ultimate eradication of HBV will be achieved in the future.
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Affiliation(s)
- Yachao Tao
- Center of Infectious Diseases, Division of Infectious Diseases, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Dongbo Wu
- Center of Infectious Diseases, Division of Infectious Diseases, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Lingyun Zhou
- Center of Infectious Diseases, Division of Infectious Diseases, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Enqiang Chen
- Center of Infectious Diseases, Division of Infectious Diseases, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Changhai Liu
- Center of Infectious Diseases, Division of Infectious Diseases, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Xiaoqiong Tang
- Center of Infectious Diseases, Division of Infectious Diseases, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Wei Jiang
- Center of Infectious Diseases, Division of Infectious Diseases, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Ning Han
- Center of Infectious Diseases, Division of Infectious Diseases, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Hong Li
- Center of Infectious Diseases, Division of Infectious Diseases, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
| | - Hong Tang
- Center of Infectious Diseases, Division of Infectious Diseases, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
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14
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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.
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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
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15
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Peng C, Jiexin L, Benhong Z. Letter: decreased neonatal hepatitis B virus (HBV) viremia by maternal tenofovir treatment predicts reduced chronic HBV infection in children born to highly viremic mothers. Aliment Pharmacol Ther 2019; 50:973-974. [PMID: 31591770 DOI: 10.1111/apt.15481] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/09/2022]
Affiliation(s)
- Chen Peng
- Department of Pharmacy, Renmin Hospital of Wuhan University, Wuhan, Hubei, P.R. China
| | - Lei Jiexin
- Department of Endocrinology, Renmin Hospital of Wuhan University, Wuhan, Hubei, P.R. China
| | - Zhou Benhong
- Department of Pharmacy, Renmin Hospital of Wuhan University, Wuhan, Hubei, P.R. China
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16
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Sali S, Darvishi M, GhasemiAdl M, Akhlaghdoust M, Mirzazadeh A, Behjati SE, Sheikh-Zeinolabedini H, Shokouhi S, Tavakolpour S. Comparing the Efficacy and Safety of Treating Chronic Hepatitis B Infection during Pregnancy with Lamivudine, Telbivudine, and Tenofovir: A Meta-analysis. J Clin Transl Hepatol 2019; 7:197-212. [PMID: 31608211 PMCID: PMC6783676 DOI: 10.14218/jcth.2019.00021] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/07/2019] [Revised: 08/13/2019] [Accepted: 08/19/2019] [Indexed: 12/14/2022] Open
Abstract
Background and Aims: The perinatal transmission of hepatitis B virus (HBV) remains an important global health problem. Here, a systematic review and meta-analysis were conducted to evaluate the evidence regarding the efficacy and maternal/fetal safety of treating pregnant women with lamivudine, telbivudine (LdT), and tenofovir (TDF). Methods: A PubMed and Scopus search resulted in 1,076 records, which were reduced to 36, containing 7,717 pregnant women with chronic HBV infection and 7467 infants meeting the inclusion criteria. The latest search was in August 2019. Results: Treatment with LdT, but not lamivudine and TDF, could significantly reduce the hepatitis B virus surface antigen-positive rate (odds ratio (OR) = 0.37) in infants; it also led to higher rates of hepatitis B e antigen loss (OR = 12.14), hepatitis B e antigen seroconversion (OR = 8.93), and alanine aminotransferase normalization in mothers (OR = 1.49). Each of these treatments was able to significantly reduce HBV DNA positivity at birth (total OR = 0.19) and mother-to-child-transmission of HBV (total OR = 0.15), and to cause higher rates of HBV DNA suppression in mothers (total OR = 25.53). However, nucleos(t)ide analogues might also be involved in creatine kinase elevation (total OR = 7.48). In contrast, no significant association was found between nucleos(t)ide analogue therapy and preterm/premature births, congenital malformation, low birth weight, and abortion or fetal/infant death. The results suggested LdT's high capability of preventing mother-to-child-transmission. However, TDF failed to show significant associations to a reduced risk of mother-to-child-transmission, probably due to the low number of patients included. Conclusions: Although using either lamivudine, LdT, or TDF could lead to more favorable maternal/fetal outcomes, LdT seemed to show more potential in resolving certain infant- and maternal-related outcomes. More studies on the safety profile of such treatments are required.
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Affiliation(s)
- Shahnaz Sali
- Infectious Diseases and Tropical Medicine Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mohammad Darvishi
- Department of Aerospace and Subaquatic Medicine, Infectious Diseases and Tropical Medicine Research Center (IDTMRC), AJA University of Medical Sciences, Tehran, Iran
- Correspondence to: Soheil Tavakolpour, Infectious Diseases and Tropical Medicine Research Center, Shahid Beheshti University of Medical Sciences, Tehran 198396-3113, Iran. Tel/Fax: +98-2122267157, E-mail: ; Mohammad Darvishi, Department of Aerospace and Subaquatic Medicine, Infectious Diseases and Tropical Medicine Research Center (IDTMRC), AJA University of Medical Sciences, Tehran, Iran. E-mail:
| | - Mojtaba GhasemiAdl
- Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Meisam Akhlaghdoust
- Pars Advanced and Minimally Invasive Medical Manners Research Center, Pars Hospital, Iran University of Medical Sciences, Tehran, Iran
| | - Azin Mirzazadeh
- Joint Bioinformatics Graduate Program, University of Arkansas Little Rock and University of Arkansas for Medical Sciences, Little Rock, AR, USA
| | - Somayeh Elikaei Behjati
- The Genetics Department at Islamic Azad University, Science and Research Branch, Tehran, Iran
| | | | - Shervin Shokouhi
- Infectious Diseases and Tropical Medicine Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Soheil Tavakolpour
- Infectious Diseases and Tropical Medicine Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
- Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran
- Correspondence to: Soheil Tavakolpour, Infectious Diseases and Tropical Medicine Research Center, Shahid Beheshti University of Medical Sciences, Tehran 198396-3113, Iran. Tel/Fax: +98-2122267157, E-mail: ; Mohammad Darvishi, Department of Aerospace and Subaquatic Medicine, Infectious Diseases and Tropical Medicine Research Center (IDTMRC), AJA University of Medical Sciences, Tehran, Iran. E-mail:
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17
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Jourdain G, Ngo-Giang-Huong N, Khamduang W. Current progress in the prevention of mother-to-child transmission of hepatitis B and resulting clinical and programmatic implications. Infect Drug Resist 2019; 12:977-987. [PMID: 31118703 PMCID: PMC6499137 DOI: 10.2147/idr.s171695] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2019] [Accepted: 03/25/2019] [Indexed: 12/14/2022] Open
Abstract
There is currently no cure for hepatitis B chronic infections. Because new hepatitis B infections result mainly from perinatal transmission, preventing mother-to-child transmission is essential to reach by 2030 the goal of hepatitis B elimination set by the World Health Organization. The universal administration of hepatitis B vaccine to all infants, regardless of maternal status, starting with the birth dose, is the cornerstone of the strategy for elimination. Additional interventions, such as hepatitis B immune globulin administered to newborns and antiviral prophylaxis administered to hepatitis B infected pregnant women, may contribute to reaching the goal earlier. Hepatitis B immune globulin may remain out for reach of many pregnant women in low- and middle-income countries due to cost and logistic issues, but antivirals are cheap and do not require a cold chain for distribution. However, it has been observed that some viruses harbor mutations associated with escape from vaccine-elicited antibodies following immunization or administration of hepatitis B immune globulin. Also, resistance associated mutations have been described for several drugs used for treatment of hepatitis B infected patients as well as for the prevention of mother-to-child transmission. Whether these mutations have the potential to compromise the prevention of mother-to-child transmission or future treatment of the mother is a question of importance. We propose a review of important recent studies assessing tenofovir disoproxil fumarate for the prevention of mother-to-child transmission, and provides detailed information on the mutations possibly relevant in this setting.
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Affiliation(s)
- Gonzague Jourdain
- Unit 174-PHPT, Institut de recherche pour le développement (IRD), Marseille, France
- Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, Thailand
- Department of Immunology and Infectious Diseases, Harvard TH Chan School of Public Health, Boston, MA, USA
| | - Nicole Ngo-Giang-Huong
- Unit 174-PHPT, Institut de recherche pour le développement (IRD), Marseille, France
- Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, Thailand
- Department of Immunology and Infectious Diseases, Harvard TH Chan School of Public Health, Boston, MA, USA
| | - Woottichai Khamduang
- Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, Thailand
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18
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Song J, Yang F, Wang S, Tikande S, Deng Y, Tang W, Cao G. Efficacy and safety of antiviral treatment on blocking the mother-to-child transmission of hepatitis B virus: A meta-analysis. J Viral Hepat 2019; 26:397-406. [PMID: 30417469 DOI: 10.1111/jvh.13036] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/24/2018] [Accepted: 10/25/2018] [Indexed: 02/06/2023]
Abstract
Nucleo(t)side analogues (NAs) have been administered as adjunctive therapy to interrupt the mother-to-child transmission (MTCT) of hepatitis B virus (HBV). The efficacy and safety of this method remain controversial. A meta-analysis was conducted to evaluate the efficacy and safety of NAs treatment during pregnancy. The differences among different agents and initiation trimesters were analysed. A total of 9228 mother-infant pairs in 59 studies (32 RCTs and 27 non-RCTs) were included in this meta-analysis. NAs significantly reduced the risk of MTCT, as indicated by seropositivity of hepatitis B surface antigen (HBsAg) (risk ratio (RR) = 0.51, 95% confidence interval (CI) 0.45-0.57) and HBV DNA in newborns (RR = 0.22, 95% CI 0.18-0.26). No differences in the efficacy of interrupting HBV MTCT were evident among lamivudine, telbivudine and tenofovir disoproxil fumarate. NA was more effective when administered from the second than from the third trimester as indicated by HBV DNA (RR: the second vs the third 0.08 vs 0.22, P = 0.010), but this effect was not evident as indicated by HBsAg (RR: the second vs the third 0.46 vs 0.53, P = 0.596). Antiviral treatment initiated from the second trimester did not confer a higher risk of safety problems in the newborns compared with treatment from the third trimester, as indicated by weight (P = 0.064), length (P = 0.491) and malformation rate (P = 0.635) of newborns. CONCLUSIONS: Lamivudine, telbivudine and tenofovir disoproxil fumarate are equally effective in blocking HBV MTCT. Antiviral treatment can be applied from the second trimester, without obvious safety concerns.
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Affiliation(s)
- Jiahui Song
- Department of Epidemiology, Second Military Medical University, Shanghai, China
| | - Fan Yang
- Department of Epidemiology, Second Military Medical University, Shanghai, China
| | - Shuo Wang
- Department of Epidemiology, Second Military Medical University, Shanghai, China
| | - Sakinatou Tikande
- Department of Epidemiology, Second Military Medical University, Shanghai, China
| | - Yang Deng
- Department of Epidemiology, Second Military Medical University, Shanghai, China
| | - Weina Tang
- Department of Epidemiology, Second Military Medical University, Shanghai, China
| | - Guangwen Cao
- Department of Epidemiology, Second Military Medical University, Shanghai, China
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19
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Kar P, Sengupta A. Synthetic therapeutics for the treatment of hepatitis B during pregnancy. Expert Opin Pharmacother 2018; 19:1771-1778. [PMID: 30273073 DOI: 10.1080/14656566.2018.1527313] [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: 10/28/2022]
Abstract
INTRODUCTION Hepatitis B infection in pregnancy mandates careful monitoring and specialized management according to the phase of hepatitis B infection. Perinatal transmission may be prevented by antiviral therapy in mothers with high viral load and timely immunoprophylaxis of the infant. AREAS COVERED This review focuses on the current first-line therapies for treating hepatitis B in pregnancy, timing of therapy, and prevention of perinatal transmission. Strategies to manage disease at the various phases and potential emerging therapies in phase III of development are also covered. Medline/PubMed and Cochrane databases were searched systematically from 1990 to April 2018 with the relevant articles selected for the review. EXPERT OPINION Universal antenatal screening for hepatitis B and strict immunoprophylaxis for infants form the cornerstones to prevent hepatitis B virus (HBV) perinatal transmission. Tenofovir is the preferred drug for treatment in pregnancy in view of its good efficacy and high barrier to resistance. Most of the data on antivirals are from cohort studies which are prone to bias and more randomized controlled trials (RCTs) are needed to establish the benefits and safety of these drugs in pregnancy. Various novel drugs are in the pipeline which may pave the way for a cure in the near future.
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Affiliation(s)
- Premashis Kar
- a Department of Gastroenterology and Hepatology , Max Super Speciality Hospital, Vaishali , Ghaziabad , India
| | - Anando Sengupta
- a Department of Gastroenterology and Hepatology , Max Super Speciality Hospital, Vaishali , Ghaziabad , India
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Dionne-Odom J, Njei B, Tita ATN. Elimination of Vertical Transmission of Hepatitis B in Africa: A Review of Available Tools and New Opportunities. Clin Ther 2018; 40:1255-1267. [PMID: 29983265 PMCID: PMC6123260 DOI: 10.1016/j.clinthera.2018.05.016] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2018] [Revised: 05/21/2018] [Accepted: 05/21/2018] [Indexed: 02/06/2023]
Abstract
PURPOSE This review article focuses on preventing vertical transmission of hepatitis B virus (HBV) among pregnant women living in sub-Saharan Africa (SSA), where disease is endemic and the estimated maternal HBV seroprevalence is >8%. Available interventions that have been studied in low- and middle-income countries are compared in terms of efficacy and effectiveness in clinical practice. Global disease-elimination targets, barriers to HBV-prevention efforts, and critical research gaps are discussed. METHODS A PubMed literature search in February 2018 identified relevant studies of interventions to reduce or prevent the transmission of HBV during pregnancy or in the peripartum period. Studies that focused on interventions that are currently available or could be made available in SSA were included. Trials conducted in SSA and other low-income countries were prioritized, although studies of interventions in middle- and high-income countries were included. FINDINGS Among 127 studies and reports included in the review, 60 included data from SSA. The most cost-effective intervention to reduce HBV infection rates in SSA is timely birth-dose vaccination followed by completion of the 3-dose infant-vaccination series. The identification and treatment of pregnant women with elevated HBV viral load to further reduce the risk for vertical transmission in SSA show promise, but efficacy and tolerability trials in Africa are lacking. IMPLICATIONS Scale-up of currently available tools is required to reach HBV disease-elimination goals in SSA. Many countries in SSA are in the process of rolling out national birth-dose vaccination campaigns; this roll out provides an opportunity to evaluate and improve processes in order to expand coverage. Early antenatal care, promotion of facility deliveries, and increased awareness of HBV prevention are also key components of prevention success. Future studies in SSA should identity an HBV-prevention package that is effective, well tolerated, and feasible and can be administered in the antenatal clinic and tailored to vertical-transmission risk.
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Affiliation(s)
- Jodie Dionne-Odom
- Department of Medicine, Division of Infectious Diseases, University of Alabama, Birmingham, Alabama.
| | - Basile Njei
- Department of Medicine, Section of Digestive Disease, Yale University, New Haven, Connecticut
| | - Alan T N Tita
- Department of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, Center for Women's Reproductive Health, University of Alabama, Birmingham, Alabama
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Mikolasevic I, Filipec-Kanizaj T, Jakopcic I, Majurec I, Brncic-Fischer A, Sobocan N, Hrstic I, Stimac T, Stimac D, Milic S. Liver Disease During Pregnancy: A Challenging Clinical Issue. Med Sci Monit 2018; 24:4080-4090. [PMID: 29905165 PMCID: PMC6034557 DOI: 10.12659/msm.907723] [Citation(s) in RCA: 66] [Impact Index Per Article: 9.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2017] [Accepted: 12/14/2017] [Indexed: 12/15/2022] Open
Abstract
One of the least studied topics in the field of obstetrics is liver disease during pregnancy, which creates a challenge for both gynecologists and hepatologists. Approximately 3% of pregnant women are affected by some form of liver disease during pregnancy. Some of these conditions can be fatal for both the mother and child. In addition, 3 types of liver disease need to be differentiated during pregnancy. One type is liver disease directly related to pregnancy, which can occur at a specific time during pregnancy. Another type is liver disease not related to pregnancy, which can occur at any time, such as viral- or drug-induced hepatitis. Furthermore, pregnancy can occur in women with pre-existing liver disease. It is essential that the clinicians are familiar with this disorder so they can respond promptly and appropriately in all of these situations, especially when emergency delivery is needed and must not be postponed.
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Affiliation(s)
- Ivana Mikolasevic
- Department of Gastroenterology, University Hospital Center (UHC) Rijeka, School of Medicine, University of Rijeka, Rijeka, Croatia
| | - Tajana Filipec-Kanizaj
- Department of Gastroenterology, University Hospital Merkur, School of Medicine, University of Zagreb, Zagreb, Croatia
| | - Ivan Jakopcic
- Department of Gastroenterology, University Hospital Center (UHC) Rijeka, School of Medicine, University of Rijeka, Rijeka, Croatia
| | - Iva Majurec
- Department of Anesthesiology and Intensive Care Unit, University Hospital Merkur, Zagreb, Croatia
| | - Alemka Brncic-Fischer
- Department of Obstetrics and Gynecology, University Hospital Center (UHC) Rijeka, Rijeka, Croatia
| | - Nikola Sobocan
- Department of Gastroenterology, University Hospital Merkur, School of Medicine, University of Zagreb, Zagreb, Croatia
| | - Irena Hrstic
- Department of Internal Medicine, General Hospital Pula, Pula, Croatia
| | - Tea Stimac
- Department of Obstetrics and Gynecology, University Hospital Center (UHC) Rijeka, Rijeka, Croatia
| | - Davor Stimac
- Department of Gastroenterology, University Hospital Center (UHC) Rijeka, School of Medicine, University of Rijeka, Rijeka, Croatia
| | - Sandra Milic
- Department of Gastroenterology, University Hospital Center (UHC) Rijeka, School of Medicine, University of Rijeka, Rijeka, Croatia
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22
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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.
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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
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23
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Zhou C, Yu Y, Yang Q, Wang H, Hou M, Jin L, Zhang F, Sheng J, Miao M, Yang X, Huang HF. Motor development delay in offspring is associated with prenatal telbivudine exposure. Medicine (Baltimore) 2018; 97:e0053. [PMID: 29489662 PMCID: PMC5851739 DOI: 10.1097/md.0000000000010053] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
Telbivudine is an orally nucleoside analog with potent and specific antihepatitis B virus (HBV) activity, and it has been reported to block mother-to-infant transmission. However, few studies have focused on the safety of prenatal exposure for offspring development.This is a prospective noninterventional study. Participants were enrolled during delivery through the Women's Hospital of Zhejiang University School of Medicine between January 2012 and September 2013. Neonate's umbilical cord arterial blood (UCAB) was collected after delivery. Hepatitis B virus DNA copy, HBV serology, alanine aminotransferase (ALT), creatine kinase (CK), creatinine (CRE), and blood urea nitrogen (BUN) were measured. The development of the offspring was evaluated by the Chinese Revision of Bayley Scales of Child Development (BSCD-CR) at 12 to 24 months old.Around 30 and 31 chronic hepatitis B mothers were recruited in untreated group (non-LdT group) and telbivudine-treatment group (LdT group), respectively, and 2 children (one in non-LdT group and 1 in LdT group) were lost in follow-up. Sixty-one normal women and their children were recruited as a normal control (control group). Compared with non-LdT group, telbivudine treatment effectively blocks HBV transmission from mother to infant. However, CK in UCAB was significantly increased in the LdT group. Moreover, children with prenatal telbivudine exposure showed lower level of serum creatinine than non-LdT group, reduction of psychomotor developmental index and increased risk of motor development delay.Prenatal telbivudine exposure is correlated with motor development delay in offspring.
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Affiliation(s)
- Chengliang Zhou
- Woman's Hospital, School of Medicine, Zhejiang University
- Key Laboratory of Reproductive Genetics, Ministry of Education
- Institute of Embryo-Fetal Original Adult Disease, School of Medicine, Shanghai Jiao Tong University, China
| | - Ying Yu
- Woman's Hospital, School of Medicine, Zhejiang University
| | - Qian Yang
- International Peace Maternal and Child Health Hospital, Shanghai Jiao Tong University
- Institute of Embryo-Fetal Original Adult Disease, School of Medicine, Shanghai Jiao Tong University, China
| | - Huihui Wang
- International Peace Maternal and Child Health Hospital, Shanghai Jiao Tong University
- Institute of Embryo-Fetal Original Adult Disease, School of Medicine, Shanghai Jiao Tong University, China
| | - Min Hou
- International Peace Maternal and Child Health Hospital, Shanghai Jiao Tong University
- Institute of Embryo-Fetal Original Adult Disease, School of Medicine, Shanghai Jiao Tong University, China
| | - Li Jin
- International Peace Maternal and Child Health Hospital, Shanghai Jiao Tong University
- Institute of Embryo-Fetal Original Adult Disease, School of Medicine, Shanghai Jiao Tong University, China
| | - Fanghong Zhang
- Woman's Hospital, School of Medicine, Zhejiang University
| | - Jiangzhong Sheng
- Department of Pathology and Pathophysiology, School of Medicine, Zhejiang University
| | - Mingfang Miao
- Woman's Hospital, School of Medicine, Zhejiang University
| | - Xiaofu Yang
- Woman's Hospital, School of Medicine, Zhejiang University
| | - He-Feng Huang
- Woman's Hospital, School of Medicine, Zhejiang University
- International Peace Maternal and Child Health Hospital, Shanghai Jiao Tong University
- Key Laboratory of Reproductive Genetics, Ministry of Education
- Institute of Embryo-Fetal Original Adult Disease, School of Medicine, Shanghai Jiao Tong University, China
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24
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Tavakolpour S, Darvishi M, Mirsafaei HS, Ghasemiadl M. Nucleoside/nucleotide analogues in the treatment of chronic hepatitis B infection during pregnancy: a systematic review. Infect Dis (Lond) 2018; 50:95-106. [PMID: 29020844 DOI: 10.1080/23744235.2017.1384957] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/31/2017] [Revised: 09/15/2017] [Accepted: 09/18/2017] [Indexed: 12/18/2022] Open
Abstract
BACKGROUND Women of childbearing age who have developed chronic hepatitis B (CHB) infection, especially HBeAg-positive highly viraemic pregnant women, are largely responsible for the familial transmission of the infection. Therefore, choosing the most effective and safest antiviral medications to manage pregnant CHB patients is of crucial importance. MATERIALS AND METHODS The PubMed and Scopus databases were searched through September 2017, for all the journal articles possessing original results regarding treatment of CHB pregnant women with any nucleos(t)ide analogue (NA) therapies, including lamivudine (LAM), adefovir (ADV), entecavir (ETV), telbivudine (LdT), and tenofovir (TDF). RESULTS After the primary search, 882 studies were recognized, and updating the searching results, 41 journal articles with original data were investigated, involving 3874 newborn infants from mothers with CHB, and their mothers completed follow-up until the delivery. The most important basic data and results regarding the efficacy of drugs, the rate of vertical transmission, safety issues associated with pairs of mothers and infants, median levels of HBV DNA, breastfeeding data, and rate of rate of vaccination success were collected. Moreover, possible key conclusion, recommendations, and learned lessons were discussed. Among the evaluated NAs, all LAM was efficient and safe. LdT was found to be very effective but had some safety concerns. In contrast, TDF had the advantages of both effectiveness and safety. CONCLUSION According to data in the literature, initiation of TDF at the trimester of pregnancy in combination with immunoprophylaxis to prevent mother-to-child transmission (MTCT) of CHB infection is strongly recommended as well as successful immunization of CHB pregnant women by anti-HBV vaccines.
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Affiliation(s)
- Soheil Tavakolpour
- a Infectious Diseases and Tropical Medicine Research Center , Shahid Beheshti University of Medical Sciences , Tehran , Iran
| | - Mohammad Darvishi
- b Department of Aerospace and Subaquatic Medicine, Infectious Diseases and Tropical Medicine Research Center (IDTMRC) , AJA University of Medical Sciences , Tehran , Iran
| | - Hajar Sadat Mirsafaei
- a Infectious Diseases and Tropical Medicine Research Center , Shahid Beheshti University of Medical Sciences , Tehran , Iran
| | - Mojtaba Ghasemiadl
- a Infectious Diseases and Tropical Medicine Research Center , Shahid Beheshti University of Medical Sciences , Tehran , Iran
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25
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Safety and efficacy of lamivudine or telbivudine started in early pregnancy for mothers with active chronic hepatitis B. Hepatol Int 2018; 12:118-125. [DOI: 10.1007/s12072-017-9839-5] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/22/2017] [Accepted: 12/19/2017] [Indexed: 01/23/2023]
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26
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Sheng Q, Ding Y, Li B, Han C, Li Y, Zhang C, Bai H, Wang J, Zhao L, Xia T, An Z, Zhang M, Dou X. Efficacy and safety of nucleos(t)ide analogues to prevent hepatitis B virus mother-to-child transmission in pregnant women with high viremia: real life practice from China. Int J Med Sci 2018; 15:796-801. [PMID: 30008589 PMCID: PMC6036077 DOI: 10.7150/ijms.25047] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/19/2018] [Accepted: 04/27/2018] [Indexed: 12/11/2022] Open
Abstract
Purpose: To evaluate the efficacy and safety of nucleos(t)ide analogues, especially telbivudine (LdT) for the prevention of mother-to-child transmission (MTCT) of hepatitis B virus (HBV) in women with high viremia. Methods: We conducted a prospective, open-label, multicenter study of LdT for treating pregnant women having high viral loads of hepatitis B virus (HBV DNA>5 log10 IU/mL) but normal levels of alanine aminotransferase (ALT). Maternal HBV DNA, HBV serologic status and ALT were measured at baseline, 4 weeks after therapy, before delivery, 4 weeks after delivery, and 12 weeks after delivery. Infant HBV serologic status and HBV DNA levels were measured at 7 months. We calculated the MTCT rate of LdT-treated and LdT-untreated groups and analyzed the efficacy and safety of LdT. Results: Ninety-one women (the treatment group) were treated with LdT, and twenty-one patients (the observation group) did not undergo antiviral therapy. The baseline HBV DNA levels were 8.15±0.82 log10 IU/mL in the treatment group, and 8.09±1.04 log10 IU/mL in the observation group. The MTCT rate was 0% in the treatment group, and 9.5% in the observation group (p=0.042). In the treatment group, HBV DNA levels were 5.02±0.74 log10 IU/mL at one month after therapy, and 3.95±0.94 log10 IU/mL before delivery. Both groups had significant differences from baseline levels in HBV DNA levels (p<0.001). In total, five patients had elevated ALT levels but without evidence of decompensate liver function. No severe adverse events or complications were observed in women or infants. Conclusions: For pregnant women with HBV DNA greater than 5 log10IU/mL, LdT therapy was effective in reducing HBV MTCT. If serum HBV DNA was detectable at delivery, discontinuation of LdT immediately was found to be safe and rarely induced off-treatment hepatitis flare.
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Affiliation(s)
- Qiuju Sheng
- Department of Infectious Disease, Shengjing Hospital, China Medical University, Shenyang 110022, China
| | - Yang Ding
- Department of Infectious Disease, Shengjing Hospital, China Medical University, Shenyang 110022, China
| | - Baijun Li
- The Sixth People's Hospital of Shenyang, Shenyang 110006, China
| | - Chao Han
- Department of Infectious Disease, Shengjing Hospital, China Medical University, Shenyang 110022, China
| | - Yanwei Li
- Department of Infectious Disease, Shengjing Hospital, China Medical University, Shenyang 110022, China
| | - Chong Zhang
- Department of Infectious Disease, Shengjing Hospital, China Medical University, Shenyang 110022, China
| | - Han Bai
- Department of Infectious Disease, Shengjing Hospital, China Medical University, Shenyang 110022, China
| | - Jingyan Wang
- Department of Infectious Disease, Shengjing Hospital, China Medical University, Shenyang 110022, China
| | - Lianrong Zhao
- Department of Infectious Disease, Shengjing Hospital, China Medical University, Shenyang 110022, China
| | - Tingting Xia
- Department of Infectious Disease, Shengjing Hospital, China Medical University, Shenyang 110022, China
| | - Ziying An
- Department of Infectious Disease, Shengjing Hospital, China Medical University, Shenyang 110022, China
| | - Mingxiang Zhang
- The Sixth People's Hospital of Shenyang, Shenyang 110006, China
| | - Xiaoguang Dou
- Department of Infectious Disease, Shengjing Hospital, China Medical University, Shenyang 110022, China
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27
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Liu J, Chen T, Zhao Y. Telbivudine therapy for gravidas with chronic hepatitis B infection and patients at risk of renal impairment. J Viral Hepat 2017; 24 Suppl 1:6-11. [PMID: 29082653 DOI: 10.1111/jvh.12787] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/25/2017] [Accepted: 08/24/2017] [Indexed: 12/12/2022]
Abstract
Hepatitis B virus infection is currently the most important cause of chronic viral hepatitis worldwide and is one of the most frequent causes of end-stage liver disease. With the international implementation of the hepatitis B vaccine and combined prophylaxis for infants born to HBsAg(+) mothers, the prevalence of hepatitis B has decreased remarkably. However, intra-uterine transmission has become a critical bottleneck for eliminating hepatitis B infection. The efficacy of nucleos(t)ide analogs on inhibiting hepatitis B replication has been widely confirmed, and the quality of life and the survival of individuals with chronic hepatitis B (CHB) have improved to a great degree. However, with the availability of long-term antiviral treatment and the ever increasing ageing population, renal disorders should be considered when choosing antiviral medicines. The antiviral efficacy and safety of telbivudine (LdT) have been shown in patients with CHB infection, and LdT is approved as a class B drug for pregnancy. Furthermore, the renal protective function of LdT has been demonstrated recently. In this review, we will focus on the efficacy and safety of LdT in gravidas with CHB infection, as well as the renal protective function of LdT in CHB patients. LdT might provide physicians with a solid option for effectively treating patients with CHB, especially gravidas or those either with or at risk of renal impairment.
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Affiliation(s)
- J Liu
- Department of Infectious Disease, the First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi, China.,Institution of Hepatitis, Xi'an Jiaotong University, Xi'an, Shaanxi, China
| | - T Chen
- Department of Infectious Disease, the First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi, China.,Institution of Hepatitis, Xi'an Jiaotong University, Xi'an, Shaanxi, China
| | - Y Zhao
- Department of Infectious Disease, the First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi, China.,Institution of Hepatitis, Xi'an Jiaotong University, Xi'an, Shaanxi, China
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28
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Li YT, Lin CS. Prevention of mother-to-child transmission of hepatitis B virus: Research progress and controversy. Shijie Huaren Xiaohua Zazhi 2017; 25:2672-2680. [DOI: 10.11569/wcjd.v25.i30.2672] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Hepatitis B virus (HBV) infection is a global health problem. Mother-to-child transmission (MTCT, also known as vertical transmission) is the main cause of chronic HBV infection. Although combined active and passive immunization has greatly reduced the vertical transmission of HBV, about 8%-10% of newborns still acquire HBV infection, especially those from hepatitis B e antigen (HBeAg) positive mothers. Previous studies have shown that high levels of HBV DNA and positive HBeAg in serum of pregnant woman may be related to the vertical transmission of HBV. Thus, the prevention of MTCT of HBV has always been a practical question that clinicians must face and urgently needs to solve. However, there is still much controversy over the following aspects: indications of antiviral therapy, drug choice, timing of initiating and ending of antiviral agents, postpartum breast-feeding and so on. This review focuses on the consensus and controversy regarding the prevention of the vertical transmission of HBV.
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Affiliation(s)
- Yi-Ting Li
- Department of Infectious Diseases, the Third Affiliated Hospital of Sun Yat-sen University; Guangdong Key Laboratory of Liver Disease Research, Guangzhou 510630, Guangdong Province, China
| | - Chao-Shuang Lin
- Department of Infectious Diseases, the Third Affiliated Hospital of Sun Yat-sen University; Guangdong Key Laboratory of Liver Disease Research, Guangzhou 510630, Guangdong Province, China
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Abstract
Chronic hepatitis B virus (HBV) infection due to mother-to-child transmission during the perinatal period remains an important global health problem. Despite standard passive-active immunoprophylaxis with hepatitis B immunoglobulin and hepatitis B vaccine in neonates, up to 8.5% of newborns still acquire HBV infection. Thus, management of chronic HBV during pregnancy and strategies to prevent mother-to-child transmission are important steps in eradicating or reducing the global burden of chronic HBV infection. To date, the management of HBV infection in pregnancy still needs careful attention because of some controversial aspects, including the influence of pregnancy on the course of HBV replication, safety of antiviral prophylaxis with nucleus(t)ide analogs, postpartum flares of hepatitis after delivery, and the safety of breastfeeding. In this review, we highlight these important issues of preventive strategies in the perinatal period.
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30
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Prevent transmission of hepatitis B from mother to child in endemic areas with appropriate screening, antiviral therapy and vaccination. DRUGS & THERAPY PERSPECTIVES 2017. [DOI: 10.1007/s40267-017-0438-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
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31
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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]
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32
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Hepatitis B During Pregnancy in Endemic Areas: Screening, Treatment, and Prevention of Mother-to-Child Transmission. Paediatr Drugs 2017; 19:173-181. [PMID: 28434087 DOI: 10.1007/s40272-017-0229-1] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
The proper management of pregnant women infected with hepatitis B virus (HBV) is necessary to prevent maternal and fetal morbidity and mortality and to protect the baby from HBV infection. In the majority of cases, vertical transmission can be prevented with a universal screening program, HBV vaccine immunoprophylaxis, and administration of hepatitis B immunoglobulin (HBIg) for babies born to mothers with HBV. However, in mothers with a high viral load (>200,000 or >1,000,000 IU/ml, depending on the guideline), the chance of immunoprophylaxis failure remains high. The standard recommendation is to give an antiviral agent during the third trimester in these patients. US FDA pregnancy category B agents such as tenofovir and telbivudine are allowed through all trimesters of pregnancy. Breastfeeding for patients who receive antiviral agents can be allowed after a risk-benefit discussion with the patient.
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Kao JH, Asselah T, Dou XG, Hamed K. Telbivudine therapy for chronic hepatitis B: A journey to identify super-responders and to optimize treatment using the roadmap model. J Gastroenterol Hepatol 2017; 32:73-81. [PMID: 27515408 DOI: 10.1111/jgh.13512] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 08/03/2016] [Indexed: 02/06/2023]
Abstract
Hepatitis B virus (HBV) infection is one of the most serious health problems worldwide with a high risk for cirrhosis and liver cancer. Several antiviral agents have been approved for the treatment of chronic hepatitis B, leading to a rapid reduction in HBV DNA and normalization of serum alanine aminotransferase levels. Telbivudine, a potent inhibitor of HBV replication, has been shown to be well tolerated. Because of the emergence of drug resistance, optimization strategies for telbivudine therapy have been shown to improve patient responses. Optimal baseline characteristics in so-called super-responders have been used to predict the virological response. Baseline HBV DNA levels < 9 log10 copies/mL (2 × 108 IU/mL) or alanine aminotransferase levels of more than or equal to twofold the upper limit of normal in HBeAg-positive patients and HBV DNA < 7 log10 copies/mL (2 × 106 IU/mL) in HBeAg-negative patients were strong predictors for virological response. In addition, the roadmap model, based on early virological response at week 24 of therapy, is considered as a powerful tool to identify patients at risk of treatment failure (HBV DNA ≥ 300 copies/mL, i.e. 60 IU/mL) and to reduce the risk of antiviral resistance. When considering pre-treatment characteristics and on-treatment responses, telbivudine may provide physicians with a wide choice of options to effectively treat patients with chronic hepatitis B, especially those with or at risk of renal impairment, or women of childbearing age.
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Affiliation(s)
- Jia-Horng Kao
- Graduate Institute of Clinical Medicine and Hepatitis Research Center, National Taiwan University College of Medicine and Hospital, Taipei, Taiwan
| | - Tarik Asselah
- Hepatology Department, AP-HP, Beaujon Hospital, University Paris Diderot and INSERM UMR1149, Centre de Recherche sur l'inflammation, Labex INFLAMEX, Clichy, France
| | - Xiao-Guang Dou
- Department of Infectious Disease, Shengjing Hospital, China Medical University, Shenyang, China
| | - Kamal Hamed
- Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, USA
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Balogh J, Victor D, Asham EH, Burroughs SG, Boktour M, Saharia A, Li X, Ghobrial RM, Monsour HP. Hepatocellular carcinoma: a review. J Hepatocell Carcinoma 2016; 3:41-53. [PMID: 27785449 PMCID: PMC5063561 DOI: 10.2147/jhc.s61146] [Citation(s) in RCA: 796] [Impact Index Per Article: 88.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is the most common primary liver malignancy and is a leading cause of cancer-related death worldwide. In the United States, HCC is the ninth leading cause of cancer deaths. Despite advances in prevention techniques, screening, and new technologies in both diagnosis and treatment, incidence and mortality continue to rise. Cirrhosis remains the most important risk factor for the development of HCC regardless of etiology. Hepatitis B and C are independent risk factors for the development of cirrhosis. Alcohol consumption remains an important additional risk factor in the United States as alcohol abuse is five times higher than hepatitis C. Diagnosis is confirmed without pathologic confirmation. Screening includes both radiologic tests, such as ultrasound, computerized tomography, and magnetic resonance imaging, and serological markers such as α-fetoprotein at 6-month intervals. Multiple treatment modalities exist; however, only orthotopic liver transplantation (OLT) or surgical resection is curative. OLT is available for patients who meet or are downstaged into the Milan or University of San Francisco criteria. Additional treatment modalities include transarterial chemoembolization, radiofrequency ablation, microwave ablation, percutaneous ethanol injection, cryoablation, radiation therapy, systemic chemotherapy, and molecularly targeted therapies. Selection of a treatment modality is based on tumor size, location, extrahepatic spread, and underlying liver function. HCC is an aggressive cancer that occurs in the setting of cirrhosis and commonly presents in advanced stages. HCC can be prevented if there are appropriate measures taken, including hepatitis B virus vaccination, universal screening of blood products, use of safe injection practices, treatment and education of alcoholics and intravenous drug users, and initiation of antiviral therapy. Continued improvement in both surgical and nonsurgical approaches has demonstrated significant benefits in overall survival. While OLT remains the only curative surgical procedure, the shortage of available organs precludes this therapy for many patients with HCC.
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Affiliation(s)
- Julius Balogh
- Sherrie and Alan Conover Center for Liver Disease and Transplantation
- Division of Transplantation, Department of Surgery
| | - David Victor
- Sherrie and Alan Conover Center for Liver Disease and Transplantation
- Department of Gastroenterology and Transplant Hepatology
- Department of Medicine, Houston Methodist Hospital, Houston, TX, USA
| | - Emad H Asham
- Sherrie and Alan Conover Center for Liver Disease and Transplantation
- Division of Transplantation, Department of Surgery
| | - Sherilyn Gordon Burroughs
- Sherrie and Alan Conover Center for Liver Disease and Transplantation
- Division of Transplantation, Department of Surgery
| | - Maha Boktour
- Sherrie and Alan Conover Center for Liver Disease and Transplantation
- Division of Transplantation, Department of Surgery
| | - Ashish Saharia
- Sherrie and Alan Conover Center for Liver Disease and Transplantation
- Division of Transplantation, Department of Surgery
| | - Xian Li
- Sherrie and Alan Conover Center for Liver Disease and Transplantation
- Division of Transplantation, Department of Surgery
| | - R Mark Ghobrial
- Sherrie and Alan Conover Center for Liver Disease and Transplantation
- Division of Transplantation, Department of Surgery
| | - Howard P Monsour
- Sherrie and Alan Conover Center for Liver Disease and Transplantation
- Department of Gastroenterology and Transplant Hepatology
- Department of Medicine, Houston Methodist Hospital, Houston, TX, USA
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Tan Z, Yin Y, Zhou J, Wu L, Xu C, Hou H. Telbivudine treatment of hepatitis B virus-infected pregnant women at different gestational stages for the prevention of mother-to-child transmission: Outcomes of telbivudine treatment during pregnancy. Medicine (Baltimore) 2016; 95:e4847. [PMID: 27749537 PMCID: PMC5059039 DOI: 10.1097/md.0000000000004847] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/11/2015] [Revised: 07/14/2016] [Accepted: 08/17/2016] [Indexed: 12/17/2022] Open
Abstract
This prospective study evaluated the viability of telbivudine for blocking mother-to-child transmission (MTCT) of hepatitis B virus (HBV) infection.Pregnant women positive for the hepatitis B surface antigen began telbivudine treatment before 14 weeks of gestation (i.e., early), between 14 and 28 weeks of gestation (late), or not at all (control). In the late-treatment group, 55 women terminated telbivudine therapy within puerperium. All neonates underwent routine hepatitis B immunoglobulin plus vaccination. Mothers and infants were followed for 7 months after birth.Pregnancy outcomes were similar among the 3 groups. HBV MTCT rates in the early and late treatment and control groups were 0, 0, and 4.69%, respectively. The rates of infant vaccination success among the 3 groups were similar, as were neonatal outcomes including birth weights, asphyxia, hyperbilirubinemia, Apgar score, birth defects, and weight and height at 7 months. Puerperal discontinuation of telbivudine did not increase the alanine transaminase value at 7 months after birth, but increased serum HBV DNA levels, and rates of positive hepatitis Be-antigen.Telbivudine treatment in HBV-infected pregnant women was associated with lower serum HBV DNA levels and reduced rates of HBV MTCT; there were no associated changes in pregnancy or neonatal outcomes at birth or 7 months after birth, or in the rate of infant vaccination success. Puerperal drug withdrawal after short-term antiviral therapy will not influence hepatic function, but may increase virus replication.
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Affiliation(s)
| | - Yuzhu Yin
- Department of Obstetrics and Gynecology, Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- Correspondence: Yuzhu Yin, Department of Obstetrics and Gynecology, Third Affiliated Hospital, Sun Yat-sen University, Guangzhou 510630, China (e-mail: )
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Pan CQ, Duan Z, Dai E, Zhang S, Han G, Wang Y, Zhang H, Zou H, Zhu B, Zhao W, Jiang H. Tenofovir to Prevent Hepatitis B Transmission in Mothers with High Viral Load. N Engl J Med 2016; 374:2324-2334. [PMID: 27305192 DOI: 10.1056/nejmoa1508660] [Citation(s) in RCA: 428] [Impact Index Per Article: 47.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
BACKGROUND Few data are available regarding the use of tenofovir disoproxil fumarate (TDF) during pregnancy for the prevention of mother-to-child transmission of hepatitis B virus (HBV). METHODS In this trial, we included 200 mothers who were positive for hepatitis B e antigen (HBeAg) and who had an HBV DNA level higher than 200,000 IU per milliliter. Participants were randomly assigned, in a 1:1 ratio, to receive usual care without antiviral therapy or to receive TDF (at an oral dose of 300 mg per day) from 30 to 32 weeks of gestation until postpartum week 4; the participants were followed until postpartum week 28. All the infants received immunoprophylaxis. The primary outcomes were the rates of mother-to-child transmission and birth defects. The secondary outcomes were the safety of TDF, the percentage of mothers with an HBV DNA level of less than 200,000 IU per milliliter at delivery, and loss or seroconversion of HBeAg or hepatitis B surface antigen at postpartum week 28. RESULTS At delivery, 68% of the mothers in the TDF group (66 of 97 women), as compared with 2% in the control group (2 of 100), had an HBV DNA level of less than 200,000 IU per milliliter (P<0.001). At postpartum week 28, the rate of mother-to-child transmission was significantly lower in the TDF group than in the control group, both in the intention-to-treat analysis (with transmission of virus to 5% of the infants [5 of 97] vs. 18% [18 of 100], P=0.007) and the per-protocol analysis (with transmission of virus to 0 vs. 7% [6 of 88], P=0.01). The maternal and infant safety profiles were similar in the TDF group and the control group, including birth-defect rates (2% [2 of 95 infants] and 1% [1 of 88], respectively; P=1.00), although more mothers in the TDF group had an increase in the creatine kinase level. After the discontinuation of TDF, alanine aminotransferase elevations above the normal range occurred more frequently in mothers in the TDF group than in those in the control group (45% [44 of 97 women] vs. 30% [30 of 100], P=0.03). The maternal HBV serologic outcomes did not differ significantly between the groups. CONCLUSIONS In a cohort of HBeAg-positive mothers with an HBV DNA level of more than 200,000 IU per milliliter during the third trimester, the rate of mother-to-child transmission was lower among those who received TDF therapy than among those who received usual care without antiviral therapy. (Funded by Gilead Sciences; ClinicalTrials.gov number, NCT01488526.).
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Affiliation(s)
- Calvin Q Pan
- From the Division of Gastroenterology and Hepatology, Department of Medicine, New York University (NYU) Langone Medical Center, NYU School of Medicine, New York (C.Q.P.); and the Center for Major Infectious Diseases (C.Q.P.) and Artificial Liver Center (Z.P.D., H.B.Z.), Beijing Youan Hospital, Capital Medical University, Beijing, the Division of Liver Diseases (E.H.D.) and the Department of Gynecology and Obstetrics (B.S.Z.), the Fifth Hospital of Shijiazhuang, Hebei Medical University, Shijiazhuang, the Department of Artificial Liver (S.Q.Z.) and Central Laboratory (W.J.Z.), Hepatobiliary Disease Hospital of Ji Lin Province, Changchun, the Department of Gynecology and Obstetrics, the Second Affiliated Hospital of the Southeast University, Nanjing (G.-R.H., H.-X.J.), the Institute for Infectious Diseases, Southwest Hospital, the Third Military Medical University, Chongqing (Y.W.), and the Department of Medicine, Nanyang Center Hospital, Nanyang, Henan (H.H.Z.) - all in China
| | - Zhongping Duan
- From the Division of Gastroenterology and Hepatology, Department of Medicine, New York University (NYU) Langone Medical Center, NYU School of Medicine, New York (C.Q.P.); and the Center for Major Infectious Diseases (C.Q.P.) and Artificial Liver Center (Z.P.D., H.B.Z.), Beijing Youan Hospital, Capital Medical University, Beijing, the Division of Liver Diseases (E.H.D.) and the Department of Gynecology and Obstetrics (B.S.Z.), the Fifth Hospital of Shijiazhuang, Hebei Medical University, Shijiazhuang, the Department of Artificial Liver (S.Q.Z.) and Central Laboratory (W.J.Z.), Hepatobiliary Disease Hospital of Ji Lin Province, Changchun, the Department of Gynecology and Obstetrics, the Second Affiliated Hospital of the Southeast University, Nanjing (G.-R.H., H.-X.J.), the Institute for Infectious Diseases, Southwest Hospital, the Third Military Medical University, Chongqing (Y.W.), and the Department of Medicine, Nanyang Center Hospital, Nanyang, Henan (H.H.Z.) - all in China
| | - Erhei Dai
- From the Division of Gastroenterology and Hepatology, Department of Medicine, New York University (NYU) Langone Medical Center, NYU School of Medicine, New York (C.Q.P.); and the Center for Major Infectious Diseases (C.Q.P.) and Artificial Liver Center (Z.P.D., H.B.Z.), Beijing Youan Hospital, Capital Medical University, Beijing, the Division of Liver Diseases (E.H.D.) and the Department of Gynecology and Obstetrics (B.S.Z.), the Fifth Hospital of Shijiazhuang, Hebei Medical University, Shijiazhuang, the Department of Artificial Liver (S.Q.Z.) and Central Laboratory (W.J.Z.), Hepatobiliary Disease Hospital of Ji Lin Province, Changchun, the Department of Gynecology and Obstetrics, the Second Affiliated Hospital of the Southeast University, Nanjing (G.-R.H., H.-X.J.), the Institute for Infectious Diseases, Southwest Hospital, the Third Military Medical University, Chongqing (Y.W.), and the Department of Medicine, Nanyang Center Hospital, Nanyang, Henan (H.H.Z.) - all in China
| | - Shuqin Zhang
- From the Division of Gastroenterology and Hepatology, Department of Medicine, New York University (NYU) Langone Medical Center, NYU School of Medicine, New York (C.Q.P.); and the Center for Major Infectious Diseases (C.Q.P.) and Artificial Liver Center (Z.P.D., H.B.Z.), Beijing Youan Hospital, Capital Medical University, Beijing, the Division of Liver Diseases (E.H.D.) and the Department of Gynecology and Obstetrics (B.S.Z.), the Fifth Hospital of Shijiazhuang, Hebei Medical University, Shijiazhuang, the Department of Artificial Liver (S.Q.Z.) and Central Laboratory (W.J.Z.), Hepatobiliary Disease Hospital of Ji Lin Province, Changchun, the Department of Gynecology and Obstetrics, the Second Affiliated Hospital of the Southeast University, Nanjing (G.-R.H., H.-X.J.), the Institute for Infectious Diseases, Southwest Hospital, the Third Military Medical University, Chongqing (Y.W.), and the Department of Medicine, Nanyang Center Hospital, Nanyang, Henan (H.H.Z.) - all in China
| | - Guorong Han
- From the Division of Gastroenterology and Hepatology, Department of Medicine, New York University (NYU) Langone Medical Center, NYU School of Medicine, New York (C.Q.P.); and the Center for Major Infectious Diseases (C.Q.P.) and Artificial Liver Center (Z.P.D., H.B.Z.), Beijing Youan Hospital, Capital Medical University, Beijing, the Division of Liver Diseases (E.H.D.) and the Department of Gynecology and Obstetrics (B.S.Z.), the Fifth Hospital of Shijiazhuang, Hebei Medical University, Shijiazhuang, the Department of Artificial Liver (S.Q.Z.) and Central Laboratory (W.J.Z.), Hepatobiliary Disease Hospital of Ji Lin Province, Changchun, the Department of Gynecology and Obstetrics, the Second Affiliated Hospital of the Southeast University, Nanjing (G.-R.H., H.-X.J.), the Institute for Infectious Diseases, Southwest Hospital, the Third Military Medical University, Chongqing (Y.W.), and the Department of Medicine, Nanyang Center Hospital, Nanyang, Henan (H.H.Z.) - all in China
| | - Yuming Wang
- From the Division of Gastroenterology and Hepatology, Department of Medicine, New York University (NYU) Langone Medical Center, NYU School of Medicine, New York (C.Q.P.); and the Center for Major Infectious Diseases (C.Q.P.) and Artificial Liver Center (Z.P.D., H.B.Z.), Beijing Youan Hospital, Capital Medical University, Beijing, the Division of Liver Diseases (E.H.D.) and the Department of Gynecology and Obstetrics (B.S.Z.), the Fifth Hospital of Shijiazhuang, Hebei Medical University, Shijiazhuang, the Department of Artificial Liver (S.Q.Z.) and Central Laboratory (W.J.Z.), Hepatobiliary Disease Hospital of Ji Lin Province, Changchun, the Department of Gynecology and Obstetrics, the Second Affiliated Hospital of the Southeast University, Nanjing (G.-R.H., H.-X.J.), the Institute for Infectious Diseases, Southwest Hospital, the Third Military Medical University, Chongqing (Y.W.), and the Department of Medicine, Nanyang Center Hospital, Nanyang, Henan (H.H.Z.) - all in China
| | - Huaihong Zhang
- From the Division of Gastroenterology and Hepatology, Department of Medicine, New York University (NYU) Langone Medical Center, NYU School of Medicine, New York (C.Q.P.); and the Center for Major Infectious Diseases (C.Q.P.) and Artificial Liver Center (Z.P.D., H.B.Z.), Beijing Youan Hospital, Capital Medical University, Beijing, the Division of Liver Diseases (E.H.D.) and the Department of Gynecology and Obstetrics (B.S.Z.), the Fifth Hospital of Shijiazhuang, Hebei Medical University, Shijiazhuang, the Department of Artificial Liver (S.Q.Z.) and Central Laboratory (W.J.Z.), Hepatobiliary Disease Hospital of Ji Lin Province, Changchun, the Department of Gynecology and Obstetrics, the Second Affiliated Hospital of the Southeast University, Nanjing (G.-R.H., H.-X.J.), the Institute for Infectious Diseases, Southwest Hospital, the Third Military Medical University, Chongqing (Y.W.), and the Department of Medicine, Nanyang Center Hospital, Nanyang, Henan (H.H.Z.) - all in China
| | - Huaibin Zou
- From the Division of Gastroenterology and Hepatology, Department of Medicine, New York University (NYU) Langone Medical Center, NYU School of Medicine, New York (C.Q.P.); and the Center for Major Infectious Diseases (C.Q.P.) and Artificial Liver Center (Z.P.D., H.B.Z.), Beijing Youan Hospital, Capital Medical University, Beijing, the Division of Liver Diseases (E.H.D.) and the Department of Gynecology and Obstetrics (B.S.Z.), the Fifth Hospital of Shijiazhuang, Hebei Medical University, Shijiazhuang, the Department of Artificial Liver (S.Q.Z.) and Central Laboratory (W.J.Z.), Hepatobiliary Disease Hospital of Ji Lin Province, Changchun, the Department of Gynecology and Obstetrics, the Second Affiliated Hospital of the Southeast University, Nanjing (G.-R.H., H.-X.J.), the Institute for Infectious Diseases, Southwest Hospital, the Third Military Medical University, Chongqing (Y.W.), and the Department of Medicine, Nanyang Center Hospital, Nanyang, Henan (H.H.Z.) - all in China
| | - Baoshen Zhu
- From the Division of Gastroenterology and Hepatology, Department of Medicine, New York University (NYU) Langone Medical Center, NYU School of Medicine, New York (C.Q.P.); and the Center for Major Infectious Diseases (C.Q.P.) and Artificial Liver Center (Z.P.D., H.B.Z.), Beijing Youan Hospital, Capital Medical University, Beijing, the Division of Liver Diseases (E.H.D.) and the Department of Gynecology and Obstetrics (B.S.Z.), the Fifth Hospital of Shijiazhuang, Hebei Medical University, Shijiazhuang, the Department of Artificial Liver (S.Q.Z.) and Central Laboratory (W.J.Z.), Hepatobiliary Disease Hospital of Ji Lin Province, Changchun, the Department of Gynecology and Obstetrics, the Second Affiliated Hospital of the Southeast University, Nanjing (G.-R.H., H.-X.J.), the Institute for Infectious Diseases, Southwest Hospital, the Third Military Medical University, Chongqing (Y.W.), and the Department of Medicine, Nanyang Center Hospital, Nanyang, Henan (H.H.Z.) - all in China
| | - Wenjing Zhao
- From the Division of Gastroenterology and Hepatology, Department of Medicine, New York University (NYU) Langone Medical Center, NYU School of Medicine, New York (C.Q.P.); and the Center for Major Infectious Diseases (C.Q.P.) and Artificial Liver Center (Z.P.D., H.B.Z.), Beijing Youan Hospital, Capital Medical University, Beijing, the Division of Liver Diseases (E.H.D.) and the Department of Gynecology and Obstetrics (B.S.Z.), the Fifth Hospital of Shijiazhuang, Hebei Medical University, Shijiazhuang, the Department of Artificial Liver (S.Q.Z.) and Central Laboratory (W.J.Z.), Hepatobiliary Disease Hospital of Ji Lin Province, Changchun, the Department of Gynecology and Obstetrics, the Second Affiliated Hospital of the Southeast University, Nanjing (G.-R.H., H.-X.J.), the Institute for Infectious Diseases, Southwest Hospital, the Third Military Medical University, Chongqing (Y.W.), and the Department of Medicine, Nanyang Center Hospital, Nanyang, Henan (H.H.Z.) - all in China
| | - Hongxiu Jiang
- From the Division of Gastroenterology and Hepatology, Department of Medicine, New York University (NYU) Langone Medical Center, NYU School of Medicine, New York (C.Q.P.); and the Center for Major Infectious Diseases (C.Q.P.) and Artificial Liver Center (Z.P.D., H.B.Z.), Beijing Youan Hospital, Capital Medical University, Beijing, the Division of Liver Diseases (E.H.D.) and the Department of Gynecology and Obstetrics (B.S.Z.), the Fifth Hospital of Shijiazhuang, Hebei Medical University, Shijiazhuang, the Department of Artificial Liver (S.Q.Z.) and Central Laboratory (W.J.Z.), Hepatobiliary Disease Hospital of Ji Lin Province, Changchun, the Department of Gynecology and Obstetrics, the Second Affiliated Hospital of the Southeast University, Nanjing (G.-R.H., H.-X.J.), the Institute for Infectious Diseases, Southwest Hospital, the Third Military Medical University, Chongqing (Y.W.), and the Department of Medicine, Nanyang Center Hospital, Nanyang, Henan (H.H.Z.) - all in China
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Njei B, Gupta N, Ewelukwa O, Ditah I, Foma M, Lim JK. Comparative efficacy of antiviral therapy in preventing vertical transmission of hepatitis B: a network meta-analysis. Liver Int 2016; 36:634-641. [PMID: 26352650 PMCID: PMC4824664 DOI: 10.1111/liv.12959] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/30/2015] [Accepted: 08/31/2015] [Indexed: 12/18/2022]
Abstract
BACKGROUND & AIMS Antiviral drugs are safe and effective in the third trimester to prevent intrauterine transmission of hepatitis B virus, and are recommended for hepatitis B virus (HBV) infected gravid mothers (between weeks 28 and 32) with high viral load, followed by postnatal hepatitis B immunization in the newborn. We estimated the comparative efficacy of antiviral drugs for prevention of vertical transmission of HBV, through a network meta-analysis of clinical trials. METHODS We conducted a comprehensive search of MEDLINE, EMBASE and published proceedings from major liver meetings from January 1980 to November 2014. We conducted pair-wise meta-analyses and Bayesian framework using Markov chain Monte Carlo methods, combining direct and indirect evidence for any given pair of treatments. RESULTS Seventeen clinical trials involving 2764 newborns of hepatitis B surface antigen seropositive mothers were eligible for analysis. There were no clinical trials involving tenofovir or entecavir. On pair-wise meta-analyses, telbivudine (hazard ratio, HR 0.12, 95% confidence interval (CI) 0.04-0.37; I(2) = 0%), and Lamivudine (HR 0.40, 95% CI 0.24-0.65; I(2) = 0%), were more effective than placebo in reducing vertical transmission of HBV in high viremic hepatitis B e antigen (HBeAg)-positive chronic Hepatitis B Chinese patients. Sensitivity analyses limited to studies with HBeAg seropositive mothers revealed similar results. CONCLUSIONS Based on a Bayesian network meta-analysis of clinical trials, combining direct and indirect treatment comparisons, telbivudine appears to be more effective than Lamivudine for preventing vertical transmission of HBV infection. Trials assessing the efficacy of tenofovir or entecavir compared to placebo or other antiviral drugs are lacking.
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Affiliation(s)
- Basile Njei
- Section of Digestive Diseases and Yale Liver Center, Yale University School of Medicine, New Haven, CT, USA
- Investigative Medicine Program, Yale Center of Clinical Investigation, New Haven, CT, USA
| | - Neil Gupta
- Section of Digestive Diseases and Yale Liver Center, Yale University School of Medicine, New Haven, CT, USA
| | - Oforbuike Ewelukwa
- Gastroenterology and Hepatology, University of Florida, Gainesville, FL, USA
| | - Ivo Ditah
- Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
| | - Munoh Foma
- Division of Clinical Pathology, University of Yaounde 1, Yaounde, Cameroon
| | - Joseph K. Lim
- Section of Digestive Diseases and Yale Liver Center, Yale University School of Medicine, New Haven, CT, USA
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Abstract
Pregnancy associated liver diseases affect up to 3% of pregnant women and are the most frequent cause of liver dysfunction in pregnancy. When severe, they are associated with significant morbidity and mortality for both mother and infant. A rapid evaluation to distinguish them from non-pregnancy related liver dysfunction is essential, in order to facilitate appropriate management. Liver disease unrelated to pregnancy can present de novo in pregnancy, or pregnancy can occur in women with preexisting liver pathology (Table 1). Research and subsequent advances in medical care have resulted in improved but still not satisfactory maternal and fetal outcomes. In this review we provide an overview of the liver diseases specific to the pregnant state and an update on their pathogenesis, treatment and outcomes. The risks of pregnancy in women with pre-existent liver pathology is detailed and recent advances in our understanding of specific risks and outcomes are discussed.
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Piratvisuth T, Han GR, Pol S, Dong Y, Trylesinski A. Comprehensive review of telbivudine in pregnant women with chronic hepatitis B. World J Hepatol 2016; 8:452-460. [PMID: 27028961 PMCID: PMC4807307 DOI: 10.4254/wjh.v8.i9.452] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/21/2015] [Revised: 02/22/2016] [Accepted: 03/14/2016] [Indexed: 02/06/2023] Open
Abstract
AIM To achieve an evidence-based conclusion regarding the safety and efficacy of telbivudine during pregnancy. METHODS A pooled analysis of data from a literature search reported 1739 pregnancy outcomes (1673 live births) from 1725 non-overlapping pregnant women treated with telbivudine. The prevalence of live birth defects (3.6/1000) was similar to that of the non-antiviral controls (3.0/1000) and not increased as compared with overall prevalence (14.5 to 60/1000). No target organ toxicity was identified. The prevalence of spontaneous abortion in pregnant women treated with telbivudine (4.2/1000) was not increased compared with the overall prevalence (16/1000). The mother-to-child transmission rate was significantly reduced in pregnant women treated with telbivudine (0.70%) compared to those treated with the non-antiviral controls (11.9%; P < 0.0001) or compared to the historical rates of hepatitis B virus (HBV)-infected population without antiviral treatment (10%-15%). RESULTS Cumulatively 489 pregnancy cases have been reported in the telbivudine pharmacovigilance database (with a cut-off date 31 August 2014), of those, 308 had known pregnancy outcomes with 249 cases of live births (239 cases of live birth without congenital anomaly and 10 cases of live birth with congenital anomaly). In the latest antiretroviral pregnancy registry report (1 January 1989 through 31 January 2015) of 27 patients exposed to telbivudine during pregnancy (18, 6 and 3 during first, second and third trimester, respectively) 19 live births were reported and there were no cases of birth defects reported. CONCLUSION Telbivudine treatment during pregnancy presents a favorable safety profile without increased rates of live birth defects, spontaneous abortion or elective termination, or fetal/neonatal toxicity. Exposure to telbivudine in the first, second and third trimester of pregnancy has been shown to significantly reduce the risk of HBV transmission from mother to child on the basis of standard immune prophylaxis procedure.
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Affiliation(s)
- Teerha Piratvisuth
- Teerha Piratvisuth, Department of Medicine, NKC Institute of Gastroenterology and Hepatology, Prince of Songkla University, Songkhla 90110, Thailand
| | - Guo Rong Han
- Teerha Piratvisuth, Department of Medicine, NKC Institute of Gastroenterology and Hepatology, Prince of Songkla University, Songkhla 90110, Thailand
| | - Stanislas Pol
- Teerha Piratvisuth, Department of Medicine, NKC Institute of Gastroenterology and Hepatology, Prince of Songkla University, Songkhla 90110, Thailand
| | - Yuhong Dong
- Teerha Piratvisuth, Department of Medicine, NKC Institute of Gastroenterology and Hepatology, Prince of Songkla University, Songkhla 90110, Thailand
| | - Aldo Trylesinski
- Teerha Piratvisuth, Department of Medicine, NKC Institute of Gastroenterology and Hepatology, Prince of Songkla University, Songkhla 90110, Thailand
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#38: Hepatitis B in pregnancy screening, treatment, and prevention of vertical transmission. Am J Obstet Gynecol 2016; 214:6-14. [PMID: 26454123 DOI: 10.1016/j.ajog.2015.09.100] [Citation(s) in RCA: 109] [Impact Index Per Article: 12.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2015] [Revised: 09/28/2015] [Accepted: 09/29/2015] [Indexed: 12/15/2022]
Abstract
Between 800,000-1.4 million people in the United States and more than 240 million people worldwide are infected with hepatitis B virus (HBV). Specific to pregnancy, an estimated prevalence of 0.7-0.9% for chronic hepatitis B infection among pregnant women in the United States has been reported, with >25,000 infants at risk for chronic infection born annually to these women. Vertical transmission of HBV from infected mothers to their fetuses or newborns, either in utero or peripartum, remains a major source of perpetuating the reservoir of chronically infected individuals globally. Universal screening for hepatitis B infection during pregnancy has been recommended for many years. Identification of pregnant women with chronic HBV infection through universal screening has had a major impact in decreasing the risk of neonatal infection. The purpose of this document is to aid clinicians in counseling their patients regarding perinatal risks and management options available to pregnant women with hepatitis B infection in the absence of coinfection with HIV. We recommend the following: (1) perform routine screening during pregnancy for HBV infection with maternal HBsAg testing (grade 1A); (2) administer hepatitis B vaccine and HBV immunoglobulin within 12 hours of birth to all newborns of HBsAg-positive mothers or those with unknown or undocumented HBsAg status, regardless of whether maternal antiviral therapy has been given during the pregnancy (grade 1A); (3) In pregnant women with HBV infection, we suggest HBV viral load testing in the third trimester (grade 2B); (4) in pregnant women with HBV infection and viral load >6-8 log 10 copies/mL, HBV-targeted maternal antiviral therapy should be considered for the purpose of decreasing the risk of intrauterine fetal infection (grade 2B); (5) in pregnant women with HBV infection who are candidates for maternal antiviral therapy, we suggest tenofovir as a first-line agent (grade 2B); (6) we recommend that women with HBV infection be encouraged to breast-feed as long as the infant receives immunoprophylaxis at birth (HBV vaccination and hepatitis B immunoglobulin) (grade 1C); (7) for HBV infected women who have an indication for genetic testing, invasive testing (eg amniocentesis or chorionic villus sampling) may be offered-counseling should include the fact that the risk for maternal-fetal transmission may increase with HBV viral load >7 log 10 IU/mL (grade 2C); and (8) we suggest cesarean delivery not be performed for the sole indication for reduction of vertical HBV transmission (grade 2C).
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He T, Jia J. Chronic HBV: which pregnant women should be treated? Liver Int 2016; 36 Suppl 1:105-8. [PMID: 26725906 DOI: 10.1111/liv.13010] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/26/2015] [Accepted: 10/28/2015] [Indexed: 12/12/2022]
Abstract
Universal HBV vaccination in infants has led to a dramatic decline of HBsAg prevalence in many parts of the world, but the positive rate of HBsAg in women of childbearing age is still high in endemic areas. Antiviral therapy during pregnancy may be indicated to control the liver disease of the mother or to prevent the MTCT. The decision on initiation, switching, continuation or stopage of the antiviral therapy should be made after careful consideration of the benefit and risk to both mothers and foetuses. For prepregnant women of childbearing age, a finite course of interferon is preferred if a pregnancy in the distant future is planned, whereas safer NAs could be started if a pregnancy in the near future is desired. For those who already started therapy with interferon or NAs before pregnancy, the switch to safer NAs is preferred. For women with newly diagnosed or with flare of CHB during pregnancy, category B NAs may be taken to treat their liver disease. For pregnant women with serum HBV DNA >10(6-7) IU/ml, safer NAs could be started in the third trimester to further the reduce MTCT rate.
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Affiliation(s)
- Tianyu He
- Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing Key Laboratory of Translational Medicine on Liver Cirrhosis & National Clinical Research Center of Digestive Diseases, Beijing, China
| | - Jidong Jia
- Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing Key Laboratory of Translational Medicine on Liver Cirrhosis & National Clinical Research Center of Digestive Diseases, Beijing, China
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Wu Q, Xu C, Li J, Li L, Yan G, Yue L, Zeng Y, Huang H, Deng G, Wang Y. Evolution and mutations of hepatitis B virus quasispecies in genotype B and C during vertical transmission. J Med Virol 2015; 88:1018-26. [PMID: 26531675 DOI: 10.1002/jmv.24424] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/02/2015] [Indexed: 12/15/2022]
Abstract
Evolution patterns of HBV QS between genotype B and C during vertical transmission are not well understood. In this study, we enrolled 10 HBV infected mother-infant pairs (four pairs with genotype B, four pairs with genotype C, and two with co-infection) without anti-viral therapy. Serum HBV DNA of mothers and infants were sequenced, HBV QS complexity and diversity were analyzed, polymorphisms and mutation sites were recorded, and phylogenetic trees were performed. Our result showed that the QS complexities in P (amino acid), C/PreC (amino acid), and PreS1 (nucleotide) gene were significantly higher in mothers than in infants in pairs with genotype C (P < 0.05), however, full-length and other genes showed non-significant differences (P > 0.05). Unlike genotype C, QS complexity of P gene (nucleotide) was significantly higher in infants than in mothers (P < 0.05) in pairs with genotype B, similarly, QS complexities of full-length and other genes (except Pre S2) were also higher in infants than in mothers but without significant differences (P > 0.05). QS diversities of full-length and most genes in genotype B were comparable between mothers and their infants (P > 0.05), in pairs with genotype C, dS of P, X, RT genes, genetic distance of Pre S1 gene (amino acid) and dN of Pre S1 gene were significant higher in mothers than in infants (P < 0.05). Several HBV mutations correlated with immune escape, e antigen loss and drug resistance were observed in infants. The results indicated that differences of HBV QS evolution patterns between genotype B and C during vertical transmission might contribute to distinct prognosis.
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Affiliation(s)
- Quanxin Wu
- Department of Infectious Diseases, Southwest Hospital, Third Military Medical University, Chongqing, China.,The Chongqing Key Laboratory for Research of Infectious Diseases, Chongqing, China.,Cadre Ward Two, Wuhan General Hospital of Guangzhou Military Command, Wuhan, China
| | - Cheng Xu
- Department of Infectious Diseases, Southwest Hospital, Third Military Medical University, Chongqing, China.,The Chongqing Key Laboratory for Research of Infectious Diseases, Chongqing, China
| | - Junnan Li
- Department of Gynecology and Obstetrics, Southwest Hospital, Third Military Medical University, Chongqing, China
| | - Li Li
- Department of Gynecology and Obstetrics, Southwest Hospital, Third Military Medical University, Chongqing, China
| | - Guohua Yan
- Department of Infectious Diseases, Southwest Hospital, Third Military Medical University, Chongqing, China.,The Chongqing Key Laboratory for Research of Infectious Diseases, Chongqing, China
| | - Liangliang Yue
- National Plateau Wetland Research Center, Southwest Forest University, Kunming, China
| | - Yi Zeng
- Department of Gynecology and Obstetrics, The First People's Hospital, Zigong, Sichuan, China
| | - Hongfei Huang
- Department of Infectious Diseases, Southwest Hospital, Third Military Medical University, Chongqing, China.,The Chongqing Key Laboratory for Research of Infectious Diseases, Chongqing, China
| | - Guohong Deng
- Department of Infectious Diseases, Southwest Hospital, Third Military Medical University, Chongqing, China.,The Chongqing Key Laboratory for Research of Infectious Diseases, Chongqing, China
| | - Yuming Wang
- Department of Infectious Diseases, Southwest Hospital, Third Military Medical University, Chongqing, China.,The Chongqing Key Laboratory for Research of Infectious Diseases, Chongqing, China
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Hollinger FB. Should Evidence-based Medicine Be Used to Design Clinical Practice Guidelines for the Prevention of Perinatal Transmission of Hepatitis B Virus From Hepatitis B e Antigen-Positive Mothers? Clin Gastroenterol Hepatol 2015; 13:1177-80. [PMID: 25701701 DOI: 10.1016/j.cgh.2015.02.016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/10/2015] [Accepted: 02/11/2015] [Indexed: 02/07/2023]
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