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1
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Wu J, Wang H, Xiang Z, Jiang C, Xu Y, Zhai G, Ling Z. Role of viral hepatitis in pregnancy and its triggering mechanism. J Transl Int Med 2024; 12:344-354. [PMID: 39360164 PMCID: PMC11444475 DOI: 10.2478/jtim-2024-0015] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/04/2024] Open
Abstract
Hepatitis viral infection can cause severe complications, even mortality in pregnant women and their offspring. Multiple studies have shown that vertical transmission can cause viral hepatitis infections in newborns, especially in hepatitis B, C, and E. Screening for hepatitis viral infection in pregnant women is essential. Once infected, pregnant women should be given timely antiviral treatments, which could effectively alleviate the disease progression and reduce adverse outcomes. Besides, the mechanism of viral hepatitis mediating adverse pregnancy outcomes has been a hot topic. Hepatitis B virus has been found to mediate both mother- to-child and parent-child transmission. Liver injury in hepatitis C virus infection is associated with immune-mediated mechanisms, which can be regulated by hormonal factors as well. The mediating mechanism of adverse maternal and infant outcomes caused by hepatitis E virus infection is mainly related to viral replication in the placenta and changes in cytokine and estrogen. Nevertheless, the specific mechanisms related to hepatitis A virus and hepatitis D virus remain unclear, and more research is needed. This review shows that the existence of viral hepatitis during pregnancy can pose certain risks for pregnant women and infants, and different interventions have been used to treat pregnant women infected with viral hepatitis. It may provide deep insight into adverse pregnancy outcomes caused by viral hepatitis and give guidance on treatment.
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Affiliation(s)
- Jian Wu
- Department of Blood Transfusion, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, 242 Guangji Road, Suzhou 215008, Jiangsu Province, China
| | - Huiqing Wang
- Department of Family Medicine, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310016, Zhejiang Province, China
| | - Ze Xiang
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Rd, City, Hangzhou 310003, Zhejiang Province, China
| | - Chun Jiang
- Department of Blood Transfusion, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, 242 Guangji Road, Suzhou 215008, Jiangsu Province, China
| | - Yunyang Xu
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Rd, City, Hangzhou 310003, Zhejiang Province, China
| | - Guanghua Zhai
- Department of Blood Transfusion, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, 242 Guangji Road, Suzhou 215008, Jiangsu Province, China
| | - Zongxin Ling
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Rd, City, Hangzhou 310003, Zhejiang Province, China
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2
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Zhao P, Zhao Y, Du M, Chen X, Lu Y. Impact of lamivudine treatment in late pregnancy on the development of the foetal immune response to hepatitis B virus: a meta-analysis in R with the metafor package. Trans R Soc Trop Med Hyg 2024; 118:264-272. [PMID: 38048279 DOI: 10.1093/trstmh/trad084] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2023] [Revised: 10/15/2023] [Accepted: 11/09/2023] [Indexed: 12/06/2023] Open
Abstract
BACKGROUND Hepatitis B virus (HBV) infection is a worldwide public health burden, especially in Asia and Africa. Concerns were raised that foetal exposure to HBV and antiretroviral therapy (ART) might suppress the innate immune response and reduce the production of hepatitis B surface antibody (HBsAb) in foetuses and infants. We therefore conducted the current study to evaluate the impact of ART on the development of the immune response to HBV in foetuses and infants. METHODS We selected lamivudine instead of telbivudine or tenofovir as the intervention measurement because it was the oldest and most widely used ART during pregnancy and its safety data have been sufficiently documented. A comprehensive search was conducted in eight electronic databases, including four Chinese and four English databases. Studies that met the following eligibility criteria were included: human randomized controlled trials (RCTs); participants in the treatment group were exclusively exposed to lamivudine; participants in the control group were exposed to placebo, no treatment or hepatitis B immunoglobulin; all participants were HBV-positive pregnant women with a high viral load and the main outcome of interest was neonatal HBsAb seropositivity. Data were tabulated and analysed using R software. RESULTS Nine RCTs were included and analysed. Compared with controls, lamivudine significantly decreased HBsAb seronegativity in the newborn within 24 h after birth (indicating the foetal immune response to HBV). Similar results were noted in infants within 6-7 months after birth and infants within 12 months (indicating the neonatal immune response to HBV vaccine). CONCLUSIONS Lamivudine treatment in late pregnancy boosted the foetal immune response to HBV in utero and enhanced the neonatal immune response to hepatitis B vaccine after birth.
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Affiliation(s)
- Peng Zhao
- Department of Obstetrics and Gynaecology, Women's Hospital, Zhejiang University School of Medicine, Zhejiang Province, 310006, Hangzhou, No. 1 Xueshi Road, China
- Zhejiang Provincial Clinical Research Center for Obstetrics and Gynecology, Zhejiang Province, 310006, Hangzhou, No. 1 Xueshi Road, China
| | - Ying Zhao
- Department of Obstetrics, the Fourth Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang Province, 322000, Yiwu, No. N1 Shangcheng Avenue, China
| | - Minmin Du
- Department of Obstetrics, the Fourth Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang Province, 322000, Yiwu, No. N1 Shangcheng Avenue, China
| | - Xiuying Chen
- Department of Obstetrics, the Fourth Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang Province, 322000, Yiwu, No. N1 Shangcheng Avenue, China
| | - Yongchao Lu
- Department of Obstetrics and Gynaecology, Women's Hospital, Zhejiang University School of Medicine, Zhejiang Province, 310006, Hangzhou, No. 1 Xueshi Road, China
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Samadi Kochaksaraei G, Shaheen AA, Seow CH, Barkema HW, Coffin CS. Tenofovir disoproxil fumarate therapy to prevent hepatitis B virus vertical transmission-A review of maternal and infant outcomes. Liver Int 2022; 42:1712-1730. [PMID: 35312156 DOI: 10.1111/liv.15249] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/04/2021] [Revised: 01/19/2022] [Accepted: 03/17/2022] [Indexed: 02/13/2023]
Abstract
Hepatitis B virus (HBV) is a global health problem. Vertical transmission of HBV from HBV surface antigen (HBsAg)-positive mothers to their infants is the most common cause of HBV infection worldwide. The use of passive-active immunoprophylaxis is >90% effective in reducing the risk of vertical transmission, but immunoprophylaxis failure can occur in infants born to mothers with high viraemia. Thus, it is recommended that pregnant women with HBV-DNA level >200 000 IU/ml receive nucleos(t)ide analogue (NA) treatment [i.e. tenofovir disoproxil fumarate (TDF), lamivudine or telbivudine] during third trimester to prevent infant immunoprophylaxis failure. TDF is recommended as the first-line therapy based on available data on efficacy, safety and resistance profile. However, maternal immunological reconstitution following parturition can increase immune-mediated flares to viral antigens that is potentially exacerbated following TDF withdrawal. In this article, we review available data on the efficacy and safety of TDF administration to prevent HBV mother-to-child transmission. We also discuss changes in maternal viral markers [i.e. HBV-DNA, HBV e antigen and HBsAg] and alanine aminotransferase during follow-up post-partum in mothers received NA to prevent HBV vertical transmission.
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Affiliation(s)
- Golasa Samadi Kochaksaraei
- Division of Gastroenterology and Hepatology, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
| | - Abdel A Shaheen
- Division of Gastroenterology and Hepatology, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.,Department of Community Health Sciences, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
| | - Cynthia H Seow
- Division of Gastroenterology and Hepatology, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.,Department of Community Health Sciences, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
| | - Herman W Barkema
- Department of Community Health Sciences, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.,Department of Production Animal Health, Faculty of Veterinary Medicine, University of Calgary, Calgary, Alberta, Canada
| | - Carla S Coffin
- Division of Gastroenterology and Hepatology, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
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4
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Zappulo E, Giaccone A, Schiano Moriello N, Gentile I. Pharmacological approaches to prevent vertical transmission of HIV and HBV. Expert Rev Clin Pharmacol 2022; 15:863-876. [PMID: 35876100 DOI: 10.1080/17512433.2022.2105202] [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: 11/04/2022]
Abstract
INTRODUCTION Mother-to-child transmission (MTCT) is mainly responsible for the global pediatric HIV and HBV epidemic. Vertical transmission can be prevented and reduced through a series of interventions at the primary healthcare level, including extensive screening of pregnant women, administration of antivirals or immune-based treatments, counselling on type of delivery and breastfeeding. AREAS COVERED In this narrative review, approved therapeutic options for the treatment of pregnant women living with HIV or HBV are discussed with special focus on efficacy and safety profiles of each agent or drug class examined. The search was performed using Medline (via PubMed), Web of Science, and Google Scholar to identify studies assessing vertical transmission of both HIV and HBV. EXPERT OPINION Elimination of MTCT of both infections is firmly endorsed by major global commitments and the integration of tailored preventive interventions into maternal and newborn health services is of strategical importance to achieve this critical target. However, further research centered on antiviral-based and immunization trials among pregnant women is urgently needed to mitigate the risk of maternal and neonatal adverse outcomes, effectively prevent transmission to the offspring and finally eliminate the pediatric HIV and HBV epidemic, one of the key global health challenges of our time.
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Affiliation(s)
- Emanuela Zappulo
- Department of Clinical Medicine and Surgery, Infectious Diseases Unit, University of Naples Federico II, Naples, Italy
| | - Agnese Giaccone
- Department of Clinical Medicine and Surgery, Infectious Diseases Unit, University of Naples Federico II, Naples, Italy
| | - Nicola Schiano Moriello
- Department of Clinical Medicine and Surgery, Infectious Diseases Unit, University of Naples Federico II, Naples, Italy
| | - Ivan Gentile
- Department of Clinical Medicine and Surgery, Infectious Diseases Unit, University of Naples Federico II, Naples, Italy
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5
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Abstract
Importance Vertical hepatitis B virus (HBV) transmission is the important route of chronic HBV infection. Although infant immunoprophylaxis is effective, a significant number of infants still become infected, most are associated with intrauterine infection. New evidences support intrauterine treatment in cases of high risk. Objective The aim of this study was to review the current evidences and recommendations for management of HBV infection in pregnancy. Evidence Acquisition Original research articles, review articles, and guidelines were reviewed. Results The management can be summarized as follows: (1) all pregnant women should be screened for hepatitis B surface antigen (HBsAg) and antibody to HBsAg. High-risk HBsAg-negative pregnant women without immunity should be vaccinated during pregnancy. (2) HBsAg-positive pregnant women should undergo further workup for liver status and indicative factors for immunoprophylaxis failure. (3) Pregnant women should be treated with HBV DNA levels greater than 200,000 IU/mL or 6 log copies/mL. (4) Antiviral drug should be started around 28 to 32 weeks. The first-line drug is tenofovir disoproxil fumarate. (5) Delivery route should be chosen based only on obstetric indications. (6) Breastfeeding is not contraindicated because it does not increase the risk of transmission in neonates with HBV vaccine and immunoglobulin administration. (7) Neonates born to HBsAg-positive mothers should receive HBV vaccine and immunoglobulin after birth as soon as possible. (8) Follow-up of the mothers and neonates is important. Beware of hepatitis flare after birth and after antiretroviral drug discontinuation; alanine transaminase assessment every 1 to 3 months until 6 months is suggested. Also, the schedule of infant vaccination and follow-up of serologic testing at 9 to 12 months old is needed.
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6
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Kühnert M, Kehl S, Pecks U, Schäfer-Graf UM, Groten T, Schild RL, Schlembach D, Schmidt M, Hamza A. Recommendations of the AGG (Task Force for Obstetrics, Section Maternal Diseases) on the Management of Maternal Hepatitis B, C and D Infection in Pregnancy. Geburtshilfe Frauenheilkd 2021; 81:390-397. [PMID: 33867560 PMCID: PMC8046515 DOI: 10.1055/a-1330-7514] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2020] [Accepted: 12/02/2020] [Indexed: 10/27/2022] Open
Abstract
These statements and recommendations should provide appropriate information about maternal and fetal routes of infection, screening, detection of risk factors, diagnostic procedures, treatment, birth planning and peripartum and postpartum management of maternal hepatitis infection and offer pointers for prenatal counselling and routine clinical care on delivery wards.
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Affiliation(s)
| | - Sven Kehl
- Frauenklinik, Friedrich Alexander Universität Erlangen-Nürnberg, Erlangen, Germany
| | | | | | - Tanja Groten
- Klinik für Frauenheilkunde und Geburtshilfe, Universitätsklinikum Jena, Jena, Germany
| | - Ralf Lothar Schild
- Klinik für Geburtshilfe und Perinatalmedizin, Diakovere Perinatalzentrum Hannover, Hannover, Germany
| | - Dietmar Schlembach
- Klinik für Geburtsmedizin, Vivantes Klinikum Neukölln-Berlin, Berlin, Germany
| | - Markus Schmidt
- Klinik für Frauenheilkunde und Geburtshilfe, Sana Kliniken Duisburg GmbH, Duisburg, Germany
| | - Amr Hamza
- Gynäkologie und Geburtshilfe, Universitätsklinikum des Saarlandes, Homburg, Germany
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7
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Sarkar M, Brady CW, Fleckenstein J, Forde KA, Khungar V, Molleston JP, Afshar Y, Terrault NA. Reproductive Health and Liver Disease: Practice Guidance by the American Association for the Study of Liver Diseases. Hepatology 2021; 73:318-365. [PMID: 32946672 DOI: 10.1002/hep.31559] [Citation(s) in RCA: 67] [Impact Index Per Article: 16.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/08/2020] [Accepted: 09/08/2020] [Indexed: 12/11/2022]
Affiliation(s)
- Monika Sarkar
- University of California, San Francisco, San Francisco, CA
| | | | | | | | | | - Jean P Molleston
- Indiana University and Riley Hospital for Children, Indianapolis, IN
| | - Yalda Afshar
- University of California, Los Angeles, Los Angeles, CA
| | - Norah A Terrault
- Keck School of Medicine, University of Southern California, Los Angeles, CA
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8
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Bierhoff M, Smolders EJ, Tarning J, Burger DM, Spijker R, Rijken MJ, Angkurawaranon C, McGready R, White NJ, Nosten F, van Vugt M. Pharmacokinetics of oral tenofovir disoproxil fumarate in pregnancy and lactation: a systematic review. Antivir Ther 2020; 24:529-540. [PMID: 31868655 DOI: 10.3851/imp3341] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/21/2019] [Indexed: 02/07/2023]
Abstract
BACKGROUND Tenofovir disoproxil fumarate (TDF), the oral prodrug of tenofovir (TFV), is advocated in pregnancy for prevention of mother-to-child transmission (PMCT) with failure of hepatitis B immunoglobulin and vaccination. The pharmacokinetics of TDF monotherapy for PMCT-HBV is important if deployment is to emulate the success of multiple antiretrovirals (ARVs) for PMCT-HIV in resource-constrained settings. METHODS This systematic review followed a protocol and is reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement (PRISMA) guidelines. We included studies that enrolled pregnant women who received oral TDF therapy as monotherapy or in combination with other ARVs: irrespective of the reason for receiving the drug (for example, HIV, HBV or pre-exposure prophylaxis); and reported pharmacokinetics. RESULTS The area under the concentration-time curve (AUC), maximum plasma concentrations (Cmax) and last measurable plasma concentration (Clast) of TFV were decreased in the second and third trimester compared with first trimester or post-partum. In none of the manuscripts was the non-pregnant HBV threshold of Cmax of 300 ng/ml reached, but the 50% effective concentration (EC50) of TFV is lower for treatment of HBV compared with HIV. The TFV concentration in breastfed infants was 0.03% of the recommended infant dose. CONCLUSIONS Most knowledge of pharmacokinetics of TFV in pregnancy results from studies on HIV involving multiple ARVs. Increased TFV clearance occurred in the second and third trimester when optimal TFV concentrations are required to maximize suppression of HBV in the window before birth. Dose or duration adjustments will be better conceptualized with concurrent analysis of the pharmacokinetics of TFV monotherapy and hepatitis B pharmacodynamics in pregnancy.
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Affiliation(s)
- Marieke Bierhoff
- Shoklo Malaria Research Unit, Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Mae Sot, Thailand.,Department of Internal Medicine and Tropical Diseases, Amsterdam University Medical Center, location Academic Medical Center Amsterdam, Amsterdam, the Netherlands
| | - Elise J Smolders
- Department of Pharmacy, Radboud University Medical Center, Nijmegen, the Netherlands.,Department of Pharmacy, Isala Hospital, Zwolle, the Netherlands
| | - Joel Tarning
- Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.,Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, UK
| | - David M Burger
- Department of Pharmacy, Radboud University Medical Center, Nijmegen, the Netherlands
| | - Rene Spijker
- Department of Internal Medicine and Tropical Diseases, Amsterdam University Medical Center, location Academic Medical Center Amsterdam, Amsterdam, the Netherlands
| | - Marcus J Rijken
- Utrecht University Medical Centre, Utrecht, the Netherlands.,Julius Centre Global Health, Utrecht, the Netherlands
| | - Chaisiri Angkurawaranon
- Department of Family Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
| | - Rose McGready
- Shoklo Malaria Research Unit, Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Mae Sot, Thailand.,Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, UK
| | - Nicholas J White
- Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, UK
| | - Francois Nosten
- Shoklo Malaria Research Unit, Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Mae Sot, Thailand.,Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, UK
| | - Michèle van Vugt
- Department of Internal Medicine and Tropical Diseases, Amsterdam University Medical Center, location Academic Medical Center Amsterdam, Amsterdam, the Netherlands
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9
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Li Y, Wang J, Yu Y, Qiu C, Li Z, Ling Q, Zhang G, Li L, Gong Y, Lu Q, Cao L, Gu T, Wang X, Zhang M, Zhang Q, Zhang H, Xu B, Shao L, Pu Y, Zhang W. Maternal antiviral treatment safeguards infants from hepatitis B transmission in contingencies of delayed immunoprophylaxis. Liver Int 2020; 40:2377-2384. [PMID: 32304160 DOI: 10.1111/liv.14479] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/12/2020] [Revised: 03/26/2020] [Accepted: 04/13/2020] [Indexed: 12/22/2022]
Abstract
BACKGROUND & AIMS Effectiveness of maternal antiviral prophylaxis in mother-to-child transmission of hepatitis B virus (HBV) has been extensively explored in studies where standard immunoprophylaxis is well secured to the newborns. This real-world study aims to test if maternal antiviral prophylaxis can safeguard the newborn when immunoprophylaxis administration was delayed or missed. METHODS Hepatitis B surface antigen-positive pregnant women were categorized into mothers with HBV DNA levels ≥2 × 105 IU/mL receiving nucleos(t)ide analogue during the third trimester; mothers with HBV DNA levels ≥2 × 105 IU/mL without antiviral treatment; and those with HBV DNA levels <2 × 105 IU/mL without antiviral treatment. The immunoprophylaxis procedure was collected and verified by the delivery medical document and logbook of biological product usage. The primary end point was the rate of chronic HBV infection (CHB) in infants. RESULTS From 2011 to 2017, 251 mother-child pairs were enrolled. Among 187 infants of mothers with HBV DNA levels ≥2 × 105 IU/mL, none developed CHB when mothers received antiviral treatment, as compared to 13.0% (10/77) of infants born to untreated mothers (P < .001). None of the infants of mothers with HBV DNA levels <2 × 105 IU/mL were infected. Stratified by the time of immunoprophylaxis administration after birth, maternal antiviral prophylaxis predominately benefited infants who failed to receive immunoprophylaxis within 24 hours (100% [6/6] vs 0% [0/2], P = .036) and those who received delayed immunoprophylaxis between 2 and 24 hours (18.8% [3/16] vs 0% [0/32], P = .032). CONCLUSIONS Antiviral prophylaxis in high viraemic mothers is effective in contingencies of missed or delayed neonatal immunoprophylaxis.
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Affiliation(s)
- Yang Li
- Department of Infectious Disease, Huashan Hospital, Fudan University, Shanghai, China
| | - Jie Wang
- Department of Infectious Disease, Taicang Affiliated Hospital of Soochow University, The First People's Hospital of Taicang, Suzhou, China
| | - Yiqi Yu
- Department of Infectious Disease, Huashan Hospital, Fudan University, Shanghai, China
| | - Chao Qiu
- Department of Infectious Disease, Huashan Hospital, Fudan University, Shanghai, China
| | - Zhonghua Li
- Department of Infectious Disease, Taicang Affiliated Hospital of Soochow University, The First People's Hospital of Taicang, Suzhou, China
| | - Qi Ling
- Department of Gynecology and Obstetrics, Taicang Affiliated Hospital of Soochow University, The First People's Hospital of Taicang, Suzhou, China
| | - Guocui Zhang
- Department of Gynecology and Obstetrics, Taicang Affiliated Hospital of Soochow University, The First People's Hospital of Taicang, Suzhou, China
| | - Li Li
- Department of Gynecology and Obstetrics, Taicang Affiliated Hospital of Soochow University, The First People's Hospital of Taicang, Suzhou, China
| | - Yinhua Gong
- Department of Infectious Disease, Taicang Affiliated Hospital of Soochow University, The First People's Hospital of Taicang, Suzhou, China
| | - Qing Lu
- Department of Infectious Disease, Taicang Affiliated Hospital of Soochow University, The First People's Hospital of Taicang, Suzhou, China
| | - Lifeng Cao
- Department of Infectious Disease, Taicang Affiliated Hospital of Soochow University, The First People's Hospital of Taicang, Suzhou, China
| | - Ting Gu
- Department of Infectious Disease, Taicang Affiliated Hospital of Soochow University, The First People's Hospital of Taicang, Suzhou, China
| | - Xin Wang
- Department of Infectious Disease, Taicang Affiliated Hospital of Soochow University, The First People's Hospital of Taicang, Suzhou, China
| | - Miaoqu Zhang
- Department of Infectious Disease, Huashan Hospital, Fudan University, Shanghai, China
| | - Qiran Zhang
- Department of Infectious Disease, Huashan Hospital, Fudan University, Shanghai, China
| | - Hanyue Zhang
- Department of Infectious Disease, Huashan Hospital, Fudan University, Shanghai, China
| | - Bin Xu
- Department of Infectious Disease, Huashan Hospital, Fudan University, Shanghai, China
| | - Lingyun Shao
- Department of Infectious Disease, Huashan Hospital, Fudan University, Shanghai, China
| | - Yonglan Pu
- Department of Infectious Disease, Taicang Affiliated Hospital of Soochow University, The First People's Hospital of Taicang, Suzhou, China
| | - Wenhong Zhang
- Department of Infectious Disease, Huashan Hospital, Fudan University, Shanghai, China.,National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan Univeristy, Shanghai, China.,State Key Laboratory of Genetic Engineering, School of Life Science, Key Laboratory of Medical Molecular Virology (MOE/MOH) and Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai, China
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10
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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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11
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Jia F, Deng F, Tong S, Li S, Ren H, Yin W. Efficacy of oral antiviral drugs to prevent mother-to-child transmission of hepatitis B virus: a network meta-analysis. Hepatol Int 2020; 14:338-346. [PMID: 32130674 DOI: 10.1007/s12072-020-10024-2] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/07/2019] [Accepted: 02/06/2020] [Indexed: 12/26/2022]
Abstract
BACKGROUND Hepatitis B is a serious global health problem. Mother-to-child transmission (MTCT) of hepatitis B virus (HBV) is a major risk factor in the endemicity of HBV infection. Oral antiviral drugs are recommended to highly viremic mothers to decrease MTCT of HBV. The present network analysis compared the efficacy of available treatments to prevent the MTCT of HBV. METHODS The electronic databases of PubMed, Embase, Web of Science, Scopus, and Wanfang data were searched for eligible studies. Pair-wise meta-analysis and Bayesian network analysis were applied to compare the efficacy of antiviral drugs. RESULTS Seventy-five studies involving 12,740 pregnant females were eligible for analysis. On pair-wise analysis, lamivudine (OR 0.15, 95% CI 0.09-0.25, I-squared = 0%), telbivudine (OR 0.07, 95% CI 0.05-0.10, I-squared = 0%) and tenofovir (OR 0.07, 95% CI 0.04-0.13, I-squared = 0%) significantly decreased the MTCT rate. Results of multiple comparisons with ranking probability based on Bayesian analysis showed that tenofovir (SUCRA = 96.83%) appeared more effective than the two other drugs. CONCLUSION In addition to active and passive immunoprophylaxis, lamivudine, telbivudine and tenofovir in highly viremic mothers can further decrease MTCT of HBV. Based on direct and indirect evidence, tenofovir appears to be more effective than the two other drugs in the prevention of HBV MTCT.
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Affiliation(s)
- Fang Jia
- Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, No.1, Yixue Road, Yuzhong District, Chongqing, 400016, China
| | - Fuxue Deng
- Department of Cardiovascular Medicine, The Second Affiliated Hospital of Xi'an Jiaotong University (Xibei Hospital), Xi'an Jiaotong University, Xi'an, Shaanxi, China
| | - Shiwen Tong
- Department of Clinical Nutrition, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Shiying Li
- Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, No.1, Yixue Road, Yuzhong District, Chongqing, 400016, China
| | - Hong Ren
- Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, No.1, Yixue Road, Yuzhong District, Chongqing, 400016, China
| | - Wenwei Yin
- Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, No.1, Yixue Road, Yuzhong District, Chongqing, 400016, China.
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12
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Hepatitis B - Vertical transmission and the prevention of mother-to-child transmission. Best Pract Res Clin Obstet Gynaecol 2020; 68:78-88. [PMID: 32249130 DOI: 10.1016/j.bpobgyn.2020.02.014] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2019] [Revised: 02/21/2020] [Accepted: 02/26/2020] [Indexed: 12/20/2022]
Abstract
Hepatitis B virus (HBV) infection is the commonest cause of chronic hepatitis, with an estimated global prevalence of 3.5%, and which leads to significant morbidity and mortality. Mother-to-child transmission (MTCT) during pregnancy is the leading form of transmission in endemic populations, and its interruption is thus crucial as the initial step in the elimination of HBV infection, notwithstanding the availability of potent antiviral medications. The risk of MTCT is dramatically reduced by timely neonatal HBV vaccination and the administration of hepatitis B immunoglobulin after birth in high-risk infants. Maternal HBV DNA quantification during pregnancy allows the assessment of the risk of newborn immunoprophylaxis failure (IF). Maternal antiviral treatment in highly viremic women can reduce the risk of IF. However, the optimal HBV DNA cutoff level for the initiation of antiviral treatment remains to be determined.
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13
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Suoh M, Tamori A, Amano-Teranishi Y, Nakai T, Enomoto M, Kawasaki Y, Kioka K, Kawada N. The Administration of Tenofovir Disoproxil Fumarate for Pregnant Japanese Women with Chronic Hepatitis B. Intern Med 2020; 59:205-210. [PMID: 31941870 PMCID: PMC7008036 DOI: 10.2169/internalmedicine.3504-19] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/13/2019] [Accepted: 07/29/2019] [Indexed: 12/16/2022] Open
Abstract
The appropriate management of hepatitis B virus (HBV) infection during pregnancy has not been established in Japan. We herein report five HBV-infected pregnant Japanese women who received tenofovir disoproxil fumarate (TDF). Two of them had been born after the introduction of nationwide immunoprophylaxis and were vertically infected with HBV, highlighting the need to address mother-to-child transmission further. In both entecavir-experienced and nucleoside/nucleotide analog-naïve mothers, TDF suppressed HBV replication without serious adverse events. All five children were free from congenital disorders, growth impairment, and HBV infection. TDF showed safety and efficacy for pregnant woman with chronic hepatitis B and might have helped prevent mother-to-child transmission.
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Affiliation(s)
- Maito Suoh
- Department of Hepatology, Osaka City General Hospital, Japan
- Department of Hepatology, Osaka City University Graduate School of Medicine, Japan
| | - Akihiro Tamori
- Department of Hepatology, Osaka City University Graduate School of Medicine, Japan
| | | | - Takashi Nakai
- Department of Hepatology, Osaka City General Hospital, Japan
| | - Masaru Enomoto
- Department of Hepatology, Osaka City University Graduate School of Medicine, Japan
| | - Yasuko Kawasaki
- Department of Hepatology, Osaka City General Hospital, Japan
| | - Kiyohide Kioka
- Department of Hepatology, Osaka City General Hospital, Japan
| | - Norifumi Kawada
- Department of Hepatology, Osaka City University Graduate School of Medicine, Japan
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14
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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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15
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Abstract
Viral infections are common complications of pregnancy. Although some infections have maternal sequelae, many viral infections can be perinatally transmitted to cause congenital or chronic infection in fetuses or infants. Treatments of such infections are geared toward reducing maternal symptoms and complications and toward preventing maternal-to-child transmission of viruses. This article reviews the treatment of herpes simplex virus, cytomegalovirus, hepatitis B and C viruses, and human immunodeficiency virus during pregnancy.
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Affiliation(s)
- Sarah C Rogan
- Maternal and Fetal Medicine Division, Department of Obstetrics, Gynecology, and Reproductive Sciences, University of Pittsburgh School of Medicine, 300 Halket Street, Pittsburgh, PA 15213, USA
| | - Richard H Beigi
- Department of Obstetrics, Gynecology, and Reproductive Sciences, University of Pittsburgh School of Medicine, University of Pittsburgh Medical Center Magee-Womens Hospital, 300 Halket Street, Pittsburgh, PA 15213, USA.
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16
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Cheung KW, Seto MTY, Lao TTH. Prevention of perinatal hepatitis B virus transmission. Arch Gynecol Obstet 2019; 300:251-259. [PMID: 31098821 DOI: 10.1007/s00404-019-05190-0] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2019] [Accepted: 05/06/2019] [Indexed: 12/30/2022]
Abstract
PURPOSE Chronic hepatitis B virus (HBV) infection remains endemic and continues to cause significant morbidity and mortality. It is a global health issue and the World Health Organization aims to eradicate HBV by 2030. Since vertical transmission accounts for the majority of chronic HBV infection, pregnancy offers an excellent opportunity to achieve complete HBV eradication by providing effective immunization of the offspring. METHODS We reviewed recent publications identified from PubMed database using a combination of the relevant keywords for HBV, pregnancy, vertical transmission, immunoprophylaxis failure and antiviral treatment. RESULTS We summarized the evidence of factors associated with, and measures to reduce and prevent maternal to child transmission, including the use of antiviral treatment during pregnancy to prevent immunoprophylaxis failure. Evidence suggested that highly viremia mother can be offered antenatal antiviral treatment to prevent immunoprophylaxis failure. We elaborated the viral load threshold to start maternal antiviral treatment and the importance of timely neonatal vaccination. A clinical algorithm to manage HBV carriers during pregnancy was proposed. CONCLUSION Eradication of HBV is achievable with optimal management of HBV carriers, especially during pregnancy by interruption of vertical transmission. Routine antenatal screening and neonatal immunoprophylaxis remain the key measures to reduce the global HBV burden, and additional antenatal antiviral treatment could further minimize the chance of persistent infection in newborns.
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Affiliation(s)
- Ka Wang Cheung
- Department of Obstetrics and Gynaecology, Queen Mary Hospital, The University of Hong Kong, 6/F, Professorial Block, 102 Pokfulam Road, Hong Kong SAR, China.
| | - Mimi Tin Yan Seto
- Department of Obstetrics and Gynaecology, Queen Mary Hospital, The University of Hong Kong, 6/F, Professorial Block, 102 Pokfulam Road, Hong Kong SAR, China
| | - Terence Tzu-Hsi Lao
- Department of Obstetrics and Gynaecology, Queen Mary Hospital, The University of Hong Kong, 6/F, Professorial Block, 102 Pokfulam Road, Hong Kong SAR, China
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17
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Abstract
Liver diseases during pregnancy pose a unique clinical challenge because they can affect the lives of both the mother and unborn child. Although severe liver disease is rare, pregnancy-related liver disease affects approximately 3% of pregnancies and can be fatal. Timely recognition and diagnosis are essential in order to institute appropriate management strategies. This article provides an overview of liver diseases during pregnancy and is divided into 2 sections: (1) liver diseases specific to pregnancy, and (2) preexisting or coincident liver diseases during pregnancy.
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Affiliation(s)
- Karen Ma
- Section of Gastroenterology, Division of Digestive Diseases, Department of Internal Medicine, Rush University Medical Center, 1725 West Harrison Street, Suite 207, Chicago, IL 60612, USA
| | - Daniel Berger
- Section of Gastroenterology, Division of Digestive Diseases, Department of Internal Medicine, Rush University Medical Center, 1725 West Harrison Street, Suite 207, Chicago, IL 60612, USA
| | - Nancy Reau
- Section of Hepatology, Division of Digestive Diseases, Department of Internal Medicine, Rush University Medical Center, 1725 West Harrison Street, Suite 319, Chicago, IL 60612, USA.
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18
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Antiviral Therapy for AECHB and Severe Hepatitis B (Liver Failure). ACUTE EXACERBATION OF CHRONIC HEPATITIS B 2019. [PMCID: PMC7498919 DOI: 10.1007/978-94-024-1603-9_5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
This chapter describes the principles of antiviral therapy, treatment strategies, medications and recommendations for AECHB, HBV-ACLF, HBV-related liver cirrhosis, HBV-related HCC, and liver transplantation.
Severe exacerbation of chronic hepatitis B is closely related to continuous HBV replication. Therefore, inhibiting HBV replication to reduce viral load may block disease progression and improve the quality of life of these patients. ETV or TDF has been recommend first-line drug for the treatment of AECHB. A hyperactive immune response due to continuous HBV replication is the main mechanism for development of severe hepatitis B. In addition to comprehensive treatment, early administration of potent nucleoside analogs can rapidly reduce HBV DNA concentration, relieve immune injury induced by HBV, and reduce liver inflammation and patient mortality. Antiviral agents have become important in the treatment of severe exacerbation of chronic hepatitis B. Long-term antiviral treatment with nucleoside analogs can delay or reverse the progress of liver cirrhosis. Virologic response, viral resistance and adverse drug reactions should be closely monitored during treatment. The treatment should be optimized for maximum effect based on each patient’s responses. Effective antiviral therapy can suppress HBV replication and reduce the incidence of HBV-related HCC. Patients with HBV-related HCC should receive individualized and optimal multidisciplinary comprehensive treatment. Anti-viral drugs with high efficacy, low resistance and low adverse drug reactions should be selected to improve the patient’s quality of life and prolong survival time. Methods to prevent HBV reinfection after liver transplantation include passive immunization (HBIG), antiviral treatment (nucleoside analogs) and active immunization (hepatitis B vaccine). Clinical trials involving sequential combination therapy with NUC and Peg-IFN have shown statistically significant decline in HBsAg levels on treatment and high rates of sustained post-treatment serologic response. Combination therapy with novel DAA and immunotherapeutic approach may hold promise to overcome both cccDNA persistence and immune escape, representing a critical step towards HBV cure.
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19
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Tziomalos K, Neokosmidis G, Mavromatidis G, Dinas K. Novel insights in the prevention of perinatal transmission of hepatitis B. World J Hepatol 2018; 10:795-798. [PMID: 30533180 PMCID: PMC6280156 DOI: 10.4254/wjh.v10.i11.795] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/29/2018] [Revised: 08/20/2018] [Accepted: 08/27/2018] [Indexed: 02/06/2023] Open
Abstract
Perinatal transmission of hepatitis B virus (HBV) infection is major contributor to the growing burden of chronic hepatitis B worldwide. Administration of HBV immunoglobulin and HBV vaccination as soon after pregnancy as possible are the mainstay of prevention of perinatal transmission of HBV infection. In women with high viral loads, antiviral prophylaxis also appears to be useful. Lamivudine, telbivudine and tenofovir have been shown to be both safe and effective in this setting but tenofovir is the first-line option due to its low potential for resistance and more favorable safety profile.
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Affiliation(s)
- Konstantinos Tziomalos
- First Propedeutic Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, AHEPA Hospital, Thessaloniki 54636, Greece
| | - Georgios Neokosmidis
- First Propedeutic Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, AHEPA Hospital, Thessaloniki 54636, Greece
| | - Georgios Mavromatidis
- Third Department of Obstetrics and Gynecology, Medical School, Aristotle University of Thessaloniki, Hippokration Hospital, Thessaloniki 54642, Greece
| | - Konstantinos Dinas
- Second Department of Obstetrics and Gynecology, Medical School, Aristotle University of Thessaloniki, Hippokration Hospital, Thessaloniki 54642, Greece
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20
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Tong MJ, Pan CQ, Han SB, Lu DS, Raman S, Hu K, Lim JK, Hann HW, Min AD. An expert consensus for the management of chronic hepatitis B in Asian Americans. Aliment Pharmacol Ther 2018; 47:1181-1200. [PMID: 29479728 PMCID: PMC5900913 DOI: 10.1111/apt.14577] [Citation(s) in RCA: 43] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/13/2017] [Revised: 10/10/2017] [Accepted: 01/27/2018] [Indexed: 12/18/2022]
Abstract
BACKGROUND Hepatitis B virus (HBV) infection is common with major clinical consequences. In Asian Americans, the HBsAg carrier rate ranges from 2% to 16% which approximates the rates from their countries of origin. Similarly, HBV is the most important cause of cirrhosis, hepatocellular carcinoma (HCC) and liver related deaths in HBsAg positive Asians worldwide. AIM To generate recommendations for the management of Asian Americans infected with HBV. METHODS These guidelines are based on relevant data derived from medical reports on HBV from Asian countries as well as from studies in the HBsAg positive Asian Americans. The guidelines herein differ from other recommendations in the treatment of both HBeAg positive and negative chronic hepatitis B (CHB), in the approach to HCC surveillance, and in the management of HBV in pregnant women. RESULTS Asian American patients, HBeAg positive or negative, with HBV DNA levels >2000 IU/mL (>104 copies/mL) and ALT values above normal are candidates for anti-viral therapy. HBeAg negative patients with HBV DNA >2000 IU/mL and normal ALT levels but who have either serum albumin <3.5 g/dL or platelet count <130 000 mm3 , basal core promoter (BCP) mutations, or who have first-degree relatives with HCC should be offered treatment. Patients with cirrhosis and detectable HBV DNA must receive life-long anti-viral therapy. Indications for treatment include pregnant women with high viraemia, coinfected patients, and those requiring immunosuppressive therapy. In HBsAg positive patients with risk factors, life-long surveillance for HCC with alpha-fetoprotein (AFP) testing and abdominal ultrasound examination at 6-month intervals is required. In CHB patients receiving HCC treatments, repeat imaging with contrast CT scan or MRI at 3-month intervals is strongly recommended. These guidelines have been assigned to a Class (reflecting benefit vs. risk) and a Level (assessing strength or certainty) of evidence. CONCLUSIONS Application of the recommendations made based on a review of the relevant literature and the opinion of a panel of Asian American physicians with expertise in HBV treatment will inform physicians and improve patient outcomes.
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Affiliation(s)
- M. J. Tong
- Pfleger Liver InstituteDivision of Digestive DiseasesDavid Geffen School of Medicine at UCLALos AngelesCAUSA,Liver CenterHuntington Medical Research InstitutesPasadenaCAUSA
| | - C. Q. Pan
- Division of Gastroenterology and HepatologyNYU Langone Medical CenterNew York University School of MedicineNew YorkNYUSA
| | - S.‐H. B. Han
- Pfleger Liver InstituteDivision of Digestive DiseasesDavid Geffen School of Medicine at UCLALos AngelesCAUSA
| | - D. S.‐K. Lu
- Department of Radiological SciencesDavid Geffen School of Medicine at UCLALos AngelesCAUSA
| | - S. Raman
- Department of Radiological SciencesDavid Geffen School of Medicine at UCLALos AngelesCAUSA
| | - K.‐Q. Hu
- Division of GI/HepatologySchool of MedicineUniversity of California, IrvineOrangeCAUSA
| | - J. K. Lim
- Yale Liver Center and Section of Digestive DiseasesYale University School of MedicineNew HavenCTUSA
| | - H. W. Hann
- Liver Disease Prevention CenterDivision of Gastroenterology and HepatologySidney Kimmel Jefferson Medical College of Thomas Jefferson UniversityPhiladelphiaPAUSA
| | - A. D. Min
- Department of MedicineIcahn School of Medicine at Mount SinaiNew YorkNYUSA
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21
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Wong GLH, Seto WK, Wong VWS, Yuen MF, Chan HLY. Review article: long-term safety of oral anti-viral treatment for chronic hepatitis B. Aliment Pharmacol Ther 2018; 47:730-737. [PMID: 29359487 DOI: 10.1111/apt.14497] [Citation(s) in RCA: 53] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/12/2017] [Revised: 11/30/2017] [Accepted: 12/11/2017] [Indexed: 02/06/2023]
Abstract
BACKGROUND Safety profile of nucleos(t)ide analogues is an important issue in view of its widespread use for decades in patients with chronic hepatitis B (CHB). AIM To review and evaluate the latest evidence on the safety profiles of the six approved nucleoside analogues. METHODS Relevant articles related to nucleoside analogue safety were selected for review following extensive language- and date-unrestricted, electronic searches of the literature. RESULTS Nephrotoxicity has been well reported in patients receiving older generations of nucleotide analogues, namely adefovir dipivoxil and tenofovir disoproxil fumarate (TDF). Yet risks of renal failure and renal replacement therapy were similar in patients treated with nucleoside analogues versus nucleotide analogues in real-life setting. Bone toxicity is closely related to nucleoside analogue effect on renal proximal tubular and phosphaturia. Real-life data demonstrated increased risk of hip fracture in patients receiving adefovir but not TDF. The newly approved tenofovir alafenamide (TAF) has improved renal and bone safety profiles compared to TDF. Long-term use of nucleoside analogues eg entecavir does not increase the risk of other cancers. Muscular toxicity may be seen in telbivudine-treated patients so regular monitoring is advised. Peripheral neuropathy and lactic acidosis are rare adverse events. Latest international guidelines support the use of TDF, telbivudine and lamivudine during pregnancy; breastfeeding is not contraindicated during TDF therapy. CONCLUSIONS Long-term safety profile of nucleoside analogues is now better defined with more data from large real-life cohorts and clinical trials with long-term follow-up. The new nucleotide analogue, TAF is now available with favourable renal and bone safety profiles.
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Affiliation(s)
- G L-H Wong
- Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, Hong Kong, China.,Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, Hong Kong, China.,State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, Hong Kong, China
| | - W-K Seto
- Department of Medicine & State Key Laboratory of Liver Research, The University of Hong Kong, Hong Kong.,Department of Medicine, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China
| | - V W-S Wong
- Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, Hong Kong, China.,Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, Hong Kong, China.,State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, Hong Kong, China
| | - M-F Yuen
- Department of Medicine & State Key Laboratory of Liver Research, The University of Hong Kong, Hong Kong.,Department of Medicine, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China
| | - H L-Y Chan
- Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, Hong Kong, China.,Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, Hong Kong, China.,State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, Hong Kong, China
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22
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Wakano Y, Sugiura T, Endo T, Ito K, Suzuki M, Tajiri H, Tanaka Y, Saitoh S. Antiviral therapy for hepatitis B virus during second pregnancies. J Obstet Gynaecol Res 2018; 44:566-569. [PMID: 29227001 DOI: 10.1111/jog.13540] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2017] [Accepted: 09/28/2017] [Indexed: 10/10/2023]
Abstract
Mother-to-child transmission of the hepatitis B virus (HBV) is a major concern for infected mothers, especially after their first child has become an HBV carrier despite immunoprophylaxis. Eight mothers whose first child had become an HBV carrier despite immunoprophylaxis were referred for antiviral therapy during the subsequent pregnancy. All pregnant women were seropositive for both the hepatitis B surface antigen and hepatitis B e antigen. In the treatment group (three receiving lamivudine and two receiving tenofovir), mother-to-child transmission of the HBV was successfully prevented in all infants (5/5). On the other hand, two of three infants became HBV carriers in the untreated group. There were no significant adverse effects in either mothers or infants. Antiviral therapy using lamivudine and tenofovir during the second pregnancy successfully prevented mother-to-child transmission of the HBV for high-risk mothers.
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Affiliation(s)
- Yasuhiro Wakano
- Department of Pediatrics and Neonatology, Graduate School of Medical Sciences, Nagoya City University, Nagoya, Japan
| | - Tokio Sugiura
- Department of Pediatrics and Neonatology, Graduate School of Medical Sciences, Nagoya City University, Nagoya, Japan
| | - Takeshi Endo
- Department of Pediatrics and Neonatology, Graduate School of Medical Sciences, Nagoya City University, Nagoya, Japan
| | - Koichi Ito
- Department of Pediatrics and Neonatology, Graduate School of Medical Sciences, Nagoya City University, Nagoya, Japan
| | - Mitsuyoshi Suzuki
- Department of Pediatrics, Juntendo University Graduate School of Medicine, Tokyo, Japan
| | - Hitoshi Tajiri
- Department of Pediatrics, Osaka General Medical Center, Osaka, Japan
| | - Yasuhito Tanaka
- Department of Virology and Liver Unit, Graduate School of Medical Sciences, Nagoya City University, Nagoya, Japan
| | - Shinji Saitoh
- Department of Pediatrics and Neonatology, Graduate School of Medical Sciences, Nagoya City University, Nagoya, Japan
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23
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Serum Aminotransferase Flares in Pregnant and Postpartum Women With Current or Prior Treatment for Chronic Hepatitis B. J Clin Gastroenterol 2018; 52:255-261. [PMID: 28323748 DOI: 10.1097/mcg.0000000000000822] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND AND AIMS Antiviral therapy is recommended for pregnant women with chronic hepatitis B (CHB) and hepatitis B virus (HBV) DNA>200,000 IU/mL, but there is less consensus on management of women who discontinue therapy in anticipation of pregnancy or who become pregnant while on therapy. The goal of this study was to describe flares in alanine aminotransferase (ALT) during pregnancy and postpartum in CHB women with current and/or prior treatment. METHODS This was a multicenter, retrospective study of 67 pregnancies in 56 CHB women treated before and/or during pregnancy. Main outcomes were frequency, severity, and resolution of ALT flare (≥5× upper limit of normal or ≥3× baseline, whichever was higher). RESULTS During pregnancy, ALT flares (95 to 1064 U/L) were observed in 16% (7/43) of women who stopped treatment before pregnancy and 31% (4/13) of women who discontinued treatment during first trimester, many of whom had high HBV DNA levels (4.9 to 8.0 log IU/mL). No flares (0/11) were observed in women who continued treatment. Postpartum ALT flares (104 to 1584 U/L) were observed in 0% (0/15) of women who were completely untreated during pregnancy, 29% (2/7) of women who discontinued treatment in first trimester, 33% (3/9) of women who stopped treatment at delivery, and 22% (4/18) of women who continued treatment postpartum. CONCLUSIONS In previously treated women with CHB, ALT flares were common during pregnancy and postpartum, especially if antiviral therapy was discontinued shortly before pregnancy, during first trimester, or at delivery. Thus, these pregnant women should be monitored closely throughout pregnancy and the early postpartum period; larger studies are needed to further characterize the natural history of HBV infection during pregnancy and postpartum.
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24
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Sarpel D, Kushner T, Carter D, Huisman T, Chiu S, Dieterich D. Mother-to-child transmission of hepatitis B and C virus: review of the epidemiology and current treatment options. Future Virol 2018. [DOI: 10.2217/fvl-2017-0069] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
Abstract
Hepatitis B and C viruses are the leading causes of liver-related morbidity and mortality throughout the world. Hepatitis B virus is predominantly transmitted perinatally, particularly in endemic areas. The rate of mother-to-child transmission of hepatitis C virus is on the rise, largely due to the increasing opioid epidemic. While there are guidelines established for the screening and treatment of pregnant females at risk for chronic hepatitis B infection, there no such guidelines or treatment options available in pregnant females with chronic hepatitis C infection. This review examines the epidemiology of mother-to-child transmission of chronic hepatitis B and C as well as the current treatment options during pregnancy and breastfeeding for both.
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Affiliation(s)
- Dost Sarpel
- Division of Infectious Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, Mount Sinai West/St Luke's Campus, 1000 10th Avenue, Clinic 2T, New York, NY 10019, USA
| | - Tatyana Kushner
- Department of Medicine, Institute of Liver Medicine, Icahn School of Medicine at Mount Sinai, Annenberg 5–04, 1468 Madison Ave Box 1123, New York, NY 10029, USA
| | - Danielle Carter
- Department of Medicine, Institute of Liver Medicine, Icahn School of Medicine at Mount Sinai, Annenberg 5–04, 1468 Madison Ave Box 1123, New York, NY 10029, USA
| | - Tsipora Huisman
- Department of Medicine, Icahn School of Medicine at Mount Sinai, 1 Gustave L Levy Place, New York, NY 10029, USA
| | - Sophia Chiu
- Department of Medicine, Icahn School of Medicine at Mount Sinai, 1 Gustave L Levy Place, New York, NY 10029, USA
| | - Douglas Dieterich
- Department of Medicine, Institute of Liver Medicine, Icahn School of Medicine at Mount Sinai, Annenberg 5–04, 1468 Madison Ave Box 1123, New York, NY 10029, USA
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25
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Burman BE, Jhaveri MA, Kowdley KV. Third-trimester tenofovir to prevent mother-to-child hepatitis B virus transmission. Indian J Med Res 2017; 146:1-4. [PMID: 29168452 PMCID: PMC5719592 DOI: 10.4103/ijmr.ijmr_315_17] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/07/2022] Open
Affiliation(s)
- Blaire E Burman
- Department of Gastroenterology & Hepatology, Virginia Mason Medical Center, Seattle, WA, USA
| | - Manan A Jhaveri
- Liver Care Network & Organ Care Research, Swedish Medical Center, Seattle, WA, USA
| | - Kris V Kowdley
- Liver Care Network & Organ Care Research, Swedish Medical Center, Seattle, WA, USA
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26
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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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27
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Burgis JC, Kong D, Salibay C, Zipprich J, Harriman K, So S. Perinatal transmission in infants of mothers with chronic hepatitis B in California. World J Gastroenterol 2017; 23:4942-4949. [PMID: 28785148 PMCID: PMC5526764 DOI: 10.3748/wjg.v23.i27.4942] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/22/2017] [Revised: 05/11/2017] [Accepted: 06/19/2017] [Indexed: 02/06/2023] Open
Abstract
AIM To evaluate maternal hepatitis B virus (HBV) DNA as risk for perinatal HBV infection among infants of HBV-infected women in California.
METHODS Retrospective analysis among infants born to hepatitis B surface antigen (HBsAg)-positive mothers who received post vaccination serologic testing (PVST) between 2005 and 2011 in California. Demographic information was collected from the California Department of Public Health Perinatal Hepatitis B Program databaseand matched to birth certificate records. HBV DNA level and hepatitis B e antigen (HBeAg) status were obtained from three large commercial laboratories in California and provider records if available and matched to mother infant pairs. Univariate analysis compared infected and uninfected infants. Multivariate analysis was restricted to infected infants and controls with complete maternal HBV DNA results using a predefined high HBV DNA level of > 2 × 107 IU/mL, a 5:1 ratio of cases to controls and a two-sided confidence level of 95%.
RESULTS A total of 17687 infants were born to HBsAg positive mothers in California between Jan 1 2005 and Dec 31, 2011. Among 11473 infants with PVST, only 125 (1.1%) were found to be HBV infected. Among these infected infants, lapses in Advisory Committee on Immunization Practices recommended post exposure prophylaxis (PEP) occurred in only 9 infants. However, PEP errors were not significantly different between infected and uninfected infants. Among the 347 uninfected and infected infants who had maternal HBeAg and HBV DNA level, case-control analysis found HBeAg positivity (70.4% vs 28.9%, OR = 46.76, 95%CI: 6.05-361.32, P < 0.001) and a maternal HBV DNA level ≥ 2 × 107 IU/mL (92.6% vs 18.5%, OR = 54.5, 95%CI: 12.22-247.55, P < 0.001) were associated with perinatal HBV infection. In multivariate logistic regression, maternal HBV DNA level ≥ 2 × 107 IU/mL was the only significant independent predictor of perinatal HBV infection.
CONCLUSION In California, transmission is low and most infected infants receive appropriate PEP and vaccination. Maternal HBV DNA ≥ 2 × 107 IU/mL is associated with high risk of perinatal infection.
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MESH Headings
- Adult
- California/epidemiology
- Case-Control Studies
- DNA, Viral/isolation & purification
- Female
- Hepatitis B Surface Antigens/isolation & purification
- Hepatitis B e Antigens/isolation & purification
- Hepatitis B virus/genetics
- Hepatitis B virus/immunology
- Hepatitis B virus/isolation & purification
- Hepatitis B, Chronic/epidemiology
- Hepatitis B, Chronic/prevention & control
- Hepatitis B, Chronic/transmission
- Hepatitis B, Chronic/virology
- Humans
- Incidence
- Infant, Newborn
- Infectious Disease Transmission, Vertical
- Male
- Mothers
- Post-Exposure Prophylaxis/methods
- Pregnancy
- Pregnancy Complications, Infectious/blood
- Pregnancy Complications, Infectious/epidemiology
- Pregnancy Complications, Infectious/prevention & control
- Pregnancy Complications, Infectious/virology
- Retrospective Studies
- Risk Factors
- Vaccination/methods
- Young Adult
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28
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Han GR, Jiang HX, Wang CM, Ding Y, Wang GJ, Yue X, Zhou L, Zhao W. Long-term safety and efficacy of telbivudine in infants born to mothers treated during the second or third trimesters of pregnancy. J Viral Hepat 2017; 24:514-521. [PMID: 28039902 DOI: 10.1111/jvh.12670] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/11/2016] [Accepted: 12/22/2016] [Indexed: 01/31/2023]
Abstract
Telbivudine, an FDA pregnancy category B drug, has been found to reduce hepatitis B virus (HBV) perinatal transmission with no safety concerns in infants aged up to 1 year. This study evaluated the long-term efficacy and safety of telbivudine in 214 infants born to 210 pregnant women with chronic hepatitis B infection who were treated with telbivudine during pregnancy (weeks 20-32 of gestation). The infants were followed for up to 5 years after birth. The efficacy endpoint was the rate of perinatal transmission, which was established by HBsAg and HBV DNA levels at 7 and 12 months. Safety endpoints included head circumference, weight, height, congenital abnormality and hospitalization rates. In addition, the Denver Developmental Screening Test was performed in 92 randomly selected infants. None of the 214 infants born to these women were infected with HBV, and all had effective serum hepatitis B surface antibody (HBsAb) levels. Compared with Chinese standard values, there were few differences in the infants' mean head circumference, weight, and height values. No birth defects were diagnosed, and the congenital abnormality rate was 0.934%. Serious adverse events requiring hospitalization occurred in 20 infants (9.35%). The qualified Denver Developmental Screening Test rate in 92 infants was 97.82%, which was comparable to a rate of 92% in normal Chinese children. Thus, treatment with telbivudine during the second or third trimesters of pregnancy safely blocked perinatal transmission of HBV. Infants born to telbivudine-treated mothers showed normal growth and development during long-term follow-up of up to 5 years.
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Affiliation(s)
- G-R Han
- Department of Gynecology and Obstetrics, The Second Affiliated Hospital of the Southeast University, Nanjing, China
| | - H-X Jiang
- Department of Gynecology and Obstetrics, The Second Affiliated Hospital of the Southeast University, Nanjing, China
| | - C-M Wang
- Department of Gynecology and Obstetrics, The Second Affiliated Hospital of the Southeast University, Nanjing, China
| | - Y Ding
- Department of Gynecology and Obstetrics, The Second Affiliated Hospital of the Southeast University, Nanjing, China
| | - G-J Wang
- Department of Gynecology and Obstetrics, The Second Affiliated Hospital of the Southeast University, Nanjing, China
| | - X Yue
- Department of Gynecology and Obstetrics, The Second Affiliated Hospital of the Southeast University, Nanjing, China
| | - L Zhou
- Department of Gynecology and Obstetrics, School of Medicine, Southeast University, Nanjing, China
| | - W Zhao
- Department of Infectious Diseases, The Second Affiliated Hospital of the Southeast University, Nanjing, China
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29
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Castillo E, Murphy K, van Schalkwyk J. N° 342-L'hépatite B et la grossesse. JOURNAL OF OBSTETRICS AND GYNAECOLOGY CANADA 2017; 39:191-201. [DOI: 10.1016/j.jogc.2017.01.018] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
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31
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Bruni R, Taliani G, Ciccaglione AR. Antiviral treatment of HBV positive pregnant women: an additional tool to reduce perinatal transmission. Pathog Glob Health 2016; 110:275-276. [PMID: 27892799 DOI: 10.1080/20477724.2016.1255375] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022] Open
Affiliation(s)
- Roberto Bruni
- a Department of Infectious, Parasitic and Immunomediated Diseases , Istituto Superiore di Sanità , Rome , Italy
| | - Gloria Taliani
- b Department of Clinical Medicine , Sapienza Università di Roma , Rome , Italy
| | - Anna Rita Ciccaglione
- a Department of Infectious, Parasitic and Immunomediated Diseases , Istituto Superiore di Sanità , Rome , Italy
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32
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Pawlowska M, Pniewska A, Pilarczyk M, Kozielewicz D, Domagalski K. Prophylaxis of vertical HBV infection. Expert Opin Drug Saf 2016; 15:1361-8. [PMID: 27402246 DOI: 10.1080/14740338.2016.1211106] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
INTRODUCTION An appropriate management of HBV infection is the best strategy to finally reduce the total burden of HBV infection. Mother-to-child transmission (MTCT) is responsible for more than one third of chronic HBV infections worldwide. Because HBV infection in infancy or early childhood often leads to chronic infection, appropriate prophylaxis and management of HBV in pregnancy is crucial to prevent MTCT. AREAS COVERED The prevention of HBV vertical transmission is a complex task and includes: universal HBV screening of pregnant women, administration of antivirals in the third trimester of pregnancy in women with high viral load and passive-active HBV immunoprophylaxis with hepatitis B vaccine and hepatitis B immune globulin in newborns of all HBV infected women. EXPERT OPINION Universal screening of pregnant women for HBV infection, early identification of HBV DNA level in HBV-infected mothers, maternal treatment with class B according to FDA antivirals and passive/active anti-HBV immunoprophylaxis to newborns of HBV-positive mothers are crucial strategies for reducing vertical HBV transmission rates. Consideration of caesarean section in order to reduce the risk of vertical HBV transmission should be recommend in HBV infected pregnant women with high viral load despite antiviral therapy or when the therapy in the third trimester of pregnancy is not available.
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Affiliation(s)
- Malgorzata Pawlowska
- a Department of Pediatric Infectious Diseases and Hepatology, Faculty of Medicine, Collegium Medicum Bydgoszcz , Nicolaus Copernicus University , Toruń , Poland
| | - Anna Pniewska
- a Department of Pediatric Infectious Diseases and Hepatology, Faculty of Medicine, Collegium Medicum Bydgoszcz , Nicolaus Copernicus University , Toruń , Poland
| | - Malgorzata Pilarczyk
- a Department of Pediatric Infectious Diseases and Hepatology, Faculty of Medicine, Collegium Medicum Bydgoszcz , Nicolaus Copernicus University , Toruń , Poland
| | - Dorota Kozielewicz
- b Department of Infectious Diseases and Hepatology, Faculty of Medicine, Collegium Medicum Bydgoszcz , Nicolaus Copernicus University , Toruń , Poland
| | - Krzysztof Domagalski
- c Centre For Modern Interdisciplinary Technologies , Nicolaus Copernicus University , Toruń , Poland
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33
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Gish RG, Sollano JD, Lapasaran A, Ong JP. Chronic hepatitis B virus in the Philippines. J Gastroenterol Hepatol 2016; 31:945-52. [PMID: 26643262 DOI: 10.1111/jgh.13258] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 11/24/2015] [Indexed: 12/21/2022]
Abstract
Multiple studies have shown a high prevalence of chronic hepatitis B (CHB) infection in the Philippines, not only in high-risk populations but also in the general population. The most recent national study estimated HBsAg seroprevalence to be 16.7%, corresponding to an estimated 7.3 million CHB adults. The factors underlying the high prevalence of CHB and its sequelae include the inadequate use of vaccination for prevention and the lack of treatment for many Filipinos. Because without medical monitoring and treatment of CHB the risk of progression to liver failure and death is 25-30%, the ultimate medical and societal costs will be very high if the Philippines fails to properly address hepatitis B infection. It will be very important to move forward with programs that can help to ensure universal vaccination of newborns, screening and vaccination nationwide, and monitoring and treatment for CHB persons. It will also be crucial to address transmission of HBV in the health-care setting (via contaminated needles and syringes and inadequately sterilized hospital equipment) and via injection drug use and tattooing. Because of the relatively low average per capita income and the lack of coverage by PhilHealth of outpatient visits and medications, there is an urgent need to move forward with a nationally supported program that includes education for both the general public and health-care workers on liver disease and screening for hepatitis viruses, followed by, as appropriate, vaccination or treatment, with expanded government coverage for these for all those who could not otherwise afford it.
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Affiliation(s)
- Robert G Gish
- Department of Medicine, Division of Gastroenterology and Hepatology, Stanford University, Stanford, California, USA.,National Viral Hepatitis Roundtable, San Francisco, California, USA.,FAIR Foundation, Palm Desert, California, USA.,Hepatitis B Foundation, Doylestown, Pennsylvania, USA
| | - Jose D Sollano
- Section of Gastroenterology, University of Santo Tomas, Manila, Philippines
| | - Alex Lapasaran
- Schools of Nursing and Medicine, University of NevadaߚReno, Nevada, Reno, USA
| | - Janus P Ong
- Section of Gastroenterology, Department of Medicine, University of the Philippines-Philippine General Hospital, Manila, Philippines
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34
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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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35
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Wang W, Wang J, Dang S, Zhuang G. Cost-effectiveness of antiviral therapy during late pregnancy to prevent perinatal transmission of hepatitis B virus. PeerJ 2016; 4:e1709. [PMID: 27042389 PMCID: PMC4811175 DOI: 10.7717/peerj.1709] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2015] [Accepted: 01/28/2016] [Indexed: 12/18/2022] Open
Abstract
Background. Hepatitis B virus (HBV) infections are perinatally transmitted from chronically infected mothers. Supplemental antiviral therapy during late pregnancy with lamivudine (LAM), telbivudine (LdT), or tenofovir (TDF) can substantially reduce perinatal HBV transmission compared to postnatal immunoprophylaxis (IP) alone. However, the cost-effectiveness of these measures is not clear. Aim. This study evaluated the cost-effectiveness from a societal perspective of supplemental antiviral agents for preventing perinatal HBV transmission in mothers with high viral load (>6 log10 copies/mL). Methods. A systematic review and network meta-analysis were performed for the risk of perinatal HBV transmission with antiviral therapies. A decision analysis was conducted to evaluate the clinical and economic outcomes in China of four competing strategies: postnatal IP alone (strategy IP), or in combination with perinatal LAM (strategy LAM + IP), LdT (strategy LdT + IP), or TDF (strategy TDF + IP). Antiviral treatments were administered from week 28 of gestation to 4 weeks after birth. Outcomes included treatment-related costs, number of infections, and quality-adjusted life years (QALYs). One- and two-way sensitivity analyses were performed to identify influential clinical and cost-related variables. Probabilistic sensitivity analyses were used to estimate the probabilities of being cost-effective for each strategy. Results. LdT + IP and TDF + IP averted the most infections and HBV-related deaths, and gained the most QALYs. IP and TDF + IP were dominated as they resulted in less or equal QALYs with higher associated costs. LdT + IP had an incremental $2,891 per QALY gained (95% CI [$932–$20,372]) compared to LAM + IP (GDP per capita for China in 2013 was $6,800). One-way sensitivity analyses showed that the cost-effectiveness of LdT + IP was only sensitive to the relative risk of HBV transmission comparing LdT + IP with LAM + IP. Probabilistic sensitivity analyses demonstrated that LdT + IP was cost-effective in most cases across willingness-to-pay range of $6,800 ∼ $20,400 per QALY gained. Conclusions. For pregnant HBV-infected women with high levels of viremia, supplemental use of LdT during late pregnancy combined with postnatal IP for infants is cost-effective in China.
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Affiliation(s)
- Wenjun Wang
- Department of Infectious Diseases, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China; Department of Epidemiology and Biostatistics, Medical School of Xi'an Jiaotong University, Xi'an, China
| | - Jingjing Wang
- Department of Pediatrics, The Second Affiliated Hospital of Xi'an Jiaotong University , Xi'an , China
| | - Shuangsuo Dang
- Department of Infectious Diseases, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China; Department of Epidemiology and Biostatistics, Medical School of Xi'an Jiaotong University, Xi'an, China
| | - Guihua Zhuang
- Department of Epidemiology and Biostatistics, Medical School of Xi'an Jiaotong University , Xi'an , China
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36
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Fouquet A, Jambon AC, Canva V, Bocket-Mouton L, Gottrand F, Subtil D. [Hepatitis B and pregnancy. Part 1. Thirteen practical issues in antenatal period]. ACTA ACUST UNITED AC 2016; 45:531-9. [PMID: 26964700 DOI: 10.1016/j.jgyn.2016.02.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2015] [Revised: 02/03/2016] [Accepted: 02/11/2016] [Indexed: 11/28/2022]
Abstract
In France, the prevalence of chronic hepatitis B is about 1% in pregnant women (usually asymptomatic carriers of HBsAg). The risk of maternal-fetal transmission of hepatitis B is particularly high when viral load measured by PCR is higher in mothers (above 7 log) or HBeAg is present. In case of maternal-fetal transmission of hepatitis B, the risk to the newborn of developing subsequent chronic hepatitis B is very high (90%), with long-term complications such as cirrhosis and hepatocellular carcinoma. The prevention of maternal-fetal transmission is based on systematic testing for hepatitis B during pregnancy, followed by serovaccination of the newborn at birth. If necessary, amniocentesis can be realised but will avoid the realization of a transplacental gesture. In case of high viral load, the establishment of a maternal antiviral treatment with lamivudine or tenofovir from 28SA can further reduce the risk of transmission. Given the low resistance it induces, tenofovir should be used preferentially.
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Affiliation(s)
- A Fouquet
- Université Nord-de-France, hôpital Jeanne-de-Flandre, CHRU de Lille, 1, rue Eugène-Avinée, 59037 Lille cedex, France.
| | - A-C Jambon
- Gynécologie-obstétrique, centre hospitalier de Tourcoing, 59200 Tourcoing, France
| | - V Canva
- Hépato-gastroentérologie, université Nord-de-France, CHRU de Lille, 59037 Lille, France
| | - L Bocket-Mouton
- Virologie, pôle biologie-pathologie, université Nord-de-France, CHRU de Lille, 59037 Lille, France
| | - F Gottrand
- Université Nord-de-France, hôpital Jeanne-de-Flandre, CHRU de Lille, 1, rue Eugène-Avinée, 59037 Lille cedex, France
| | - D Subtil
- Université Nord-de-France, hôpital Jeanne-de-Flandre, CHRU de Lille, 1, rue Eugène-Avinée, 59037 Lille cedex, France; EA 2694, PRES université Lille-Nord-de-France, 59000 Lille, France
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Yi P, Chen R, Huang Y, Zhou RR, Fan XG. Management of mother-to-child transmission of hepatitis B virus: Propositions and challenges. J Clin Virol 2016; 77:32-9. [PMID: 26895227 DOI: 10.1016/j.jcv.2016.02.003] [Citation(s) in RCA: 59] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2015] [Revised: 01/26/2016] [Accepted: 02/04/2016] [Indexed: 02/07/2023]
Abstract
Chronic hepatitis B virus (HBV) infection due to mother-to-child transmission (MTCT) during perinatal period remains an important global health problem. Despite standard passive-active immunoprophylaxis with hepatitis B immunoglobulin (HBIG) and hepatitis B vaccine in neonates, up to 9% of newborns still acquire HBV infection, especially these from hepatitis B e antigen (HBeAg) positive mothers. Management of HBV infection in pregnancy still need to draw careful attention because of some controversial aspects, including the failure of passive-active immunoprophylaxis in a fraction of newborns, the effect and necessity of periodical hepatitis B immunoglobulin (HBIG) injection to the mothers, the safety of antiviral prophylaxis with nucleoside/nucleotide analogs, the benefit of different delivery ways, and the safety of breastfeeding. In this review, we highlight these unsettled issues of preventive strategies in perinatal period, and we further aim to provide an optimal approach to the management of preventing MTCT of HBV infection.
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Affiliation(s)
- Panpan Yi
- Department of Infectious Diseases, Key Laboratory of Viral Hepatitis of Hunan, Xiangya Hospital, Central South University, Changsha 410008, China
| | - Ruochan Chen
- Department of Infectious Diseases, Key Laboratory of Viral Hepatitis of Hunan, Xiangya Hospital, Central South University, Changsha 410008, China
| | - Yan Huang
- Department of Infectious Diseases, Key Laboratory of Viral Hepatitis of Hunan, Xiangya Hospital, Central South University, Changsha 410008, China
| | - Rong-Rong Zhou
- Department of Infectious Diseases, Key Laboratory of Viral Hepatitis of Hunan, Xiangya Hospital, Central South University, Changsha 410008, China.
| | - Xue-Gong Fan
- Department of Infectious Diseases, Key Laboratory of Viral Hepatitis of Hunan, Xiangya Hospital, Central South University, Changsha 410008, China.
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38
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Visvanathan K, Dusheiko G, Giles M, Wong ML, Phung N, Walker S, Le S, Lim SG, Gane E, Ngu M, Hardikar W, Cowie B, Bowden S, Strasser S, Levy M, Sasaduesz J. Managing HBV in pregnancy. Prevention, prophylaxis, treatment and follow-up: position paper produced by Australian, UK and New Zealand key opinion leaders. Gut 2016; 65:340-50. [PMID: 26475631 DOI: 10.1136/gutjnl-2015-310317] [Citation(s) in RCA: 55] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/09/2015] [Accepted: 09/11/2015] [Indexed: 12/13/2022]
Abstract
Hepatitis B during pregnancy presents unique management issues for both the mother and fetus. These include the lack of a current cohesive strategy for treatment and follow-up of mothers and their babies; the uncertain risk of postpartum HBV flares; the lack of randomised trial data on the safety and efficacy of antiviral treatment in pregnancy; the lack of head-to-head studies comparing different antivirals in pregnancy; and the lack of epidemiologic information regarding infection across different populations globally. This position paper provides a comprehensive review of the management of women with HBV infection prior to conception, throughout each stage of pregnancy and postpartum, as well as recommendations and clinical approaches for the follow-up of children born to infected mothers, based on available evidence in the literature and recommendations from international experts. Prevention of perinatal transmission is an important component of global efforts to reduce the burden of chronic HBV since vertical transmission is responsible for most of the chronic infection worldwide.
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Affiliation(s)
- Kumar Visvanathan
- St. Vincent's Hospital, Fitzroy, Australia Department of Medicine, University of Melbourne, Melbourne, Victoria, Australia
| | - Geoff Dusheiko
- Institute of Liver and Digestive Health, Royal Free Hospital London, London, UK
| | - Michelle Giles
- Department of Infectious Diseases and Department of Obstetrics and Gynaecology Monash Health, The Alfred Hospital, The Royal Women's Hospital, Melbourne, Victoria, Australia
| | - May-Ling Wong
- Department of Gastroenterology, Box Hill Hospital, Melbourne, Victoria, Australia
| | - Nghi Phung
- Liver Addiction Research Unit and Storr Liver Unit, Westmead Millennium Institute, University of Sydney and Westmead Hospital, Westmead, New South Wales, Australia Drug Health Western Sydney Local Health District, Westmead, New South Wales, Australia
| | - Susan Walker
- Department of Obstetrics and Gynecology, University of Melbourne, Melbourne, Victoria, Australia Department of Perinatal Medicine, Mercy Hospital for Women, Melbourne, Victoria, Australia
| | - Suong Le
- Department of Gastroenterology and Hepatology, Monash Health, Melbourne, Victoria, Australia
| | - Seng Gee Lim
- Department of Hepatology, National University Health System, Singapore, Singapore
| | - Ed Gane
- Liver Transplant Unit, Auckland City Hospital Auckland, Auckland, New Zealand
| | - Meng Ngu
- Gastroenterology and Hepatology Department, Concord Repatriation General Hospital, Sydney, New South Wales, Australia
| | - Winita Hardikar
- Department of Gastroenterology, Royal Children's Hospital, Melbourne, Victoria, Australia Department of Paediatrics, University of Melbourne, Melbourne, Victoria, Australia Murdoch Childrens Research Institute, Parkville, Victoria, Australia
| | - Ben Cowie
- Department of Infectious Diseases, Royal Melbourne Hospital, Melbourne, Victoria, Australia Victorian Infectious Disease Reference Laboratory, Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia
| | - Scott Bowden
- Victorian Infectious Disease Reference Laboratory, Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia
| | - Simone Strasser
- AW Morrow Gastroenterology and Liver Centre, Royal Prince Alfred Hospital, Camperdown, Australia
| | - Miriam Levy
- Liverpool Hospital, Sydney, New South Wales, Australia Department of Medicine, University of NSW, Sydney, New South Wales, Australia
| | - Joe Sasaduesz
- Department of Infectious Diseases, Royal Melbourne Hospital, Melbourne, Victoria, Australia
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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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Brown RS, McMahon BJ, Lok ASF, Wong JB, Ahmed AT, Mouchli MA, Wang Z, Prokop LJ, Murad MH, Mohammed K. Antiviral therapy in chronic hepatitis B viral infection during pregnancy: A systematic review and meta-analysis. Hepatology 2016; 63:319-33. [PMID: 26565396 DOI: 10.1002/hep.28302] [Citation(s) in RCA: 231] [Impact Index Per Article: 25.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/18/2015] [Accepted: 10/15/2015] [Indexed: 12/11/2022]
Abstract
UNLABELLED Perinatal or mother-to-child transmission (MTCT) of hepatitis B virus (HBV) remains the major risk factor for chronic HBV infection worldwide. In addition to hepatitis B immune globulin and vaccination, oral antiviral therapies in highly viremic mothers can further decrease MTCT of HBV. We conducted a systematic review and meta-analysis to synthesize the evidence on the efficacy and maternal and fetal safety of antiviral therapy during pregnancy. A protocol was developed by the American Association for the Study of Liver Diseases guideline writing committee. We searched multiple databases for controlled studies that enrolled pregnant women with chronic HBV infection treated with antiviral therapy. Outcomes of interest were reduction of MTCT and adverse outcomes to mothers and newborns. Study selection and data extraction were done by pairs of independent reviewers. We included 26 studies that enrolled 3622 pregnant women. Antiviral therapy reduced MTCT, as defined by infant hepatitis B surface antigen seropositivity (risk ratio = 0.3, 95% confidence interval 0.2-0.4) or infant HBV DNA seropositivity (risk ratio = 0.3, 95% confidence interval 0.2-0.5) at 6-12 months. No significant differences were found in the congenital malformation rate, prematurity rate, and Apgar scores. Compared to control, lamivudine or telbivudine improved maternal HBV DNA suppression at delivery and during 4-8 weeks' postpartum follow-up. Tenofovir showed improvement in HBV DNA suppression at delivery. No significant differences were found in postpartum hemorrhage, cesarean section, and elevated creatinine kinase rates. CONCLUSIONS Antiviral therapy improves HBV suppression and reduces MTCT in women with chronic HBV infection with high viral load compared to the use of hepatitis B immunoglobulin and vaccination alone; the use of telbivudine, lamivudine, and tenofovir appears to be safe in pregnancy with no increased adverse maternal or fetal outcome.
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Affiliation(s)
- Robert S Brown
- Division of Gastroenterology and Hepatology, Weill Cornell Medical College, New York, NY
| | - Brian J McMahon
- Liver Diseases and Hepatitis Program, Alaska Native Tribal Health Consortium, Anchorage, AK
| | - Anna S F Lok
- Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, MI
| | - John B Wong
- Division of Clinical Decision Making, Tufts Medical Center, Boston, MA
| | - Ahmed T Ahmed
- Evidence-Based Practice Research Program.,Center for the Science of Health Care Delivery
| | | | - Zhen Wang
- Evidence-Based Practice Research Program.,Center for the Science of Health Care Delivery
| | | | - Mohammad Hassan Murad
- Evidence-Based Practice Research Program.,Center for the Science of Health Care Delivery.,Division of Preventive, Occupational and Aerospace Medicine, Mayo Clinic, Rochester, MN
| | - Khaled Mohammed
- Evidence-Based Practice Research Program.,Center for the Science of Health Care Delivery.,Division of Preventive, Occupational and Aerospace Medicine, Mayo Clinic, Rochester, MN
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Samadi Kochaksaraei G, Castillo E, Osman M, Simmonds K, Scott AN, Oshiomogho JI, Lee SS, Myers RP, Martin SR, Coffin CS. Clinical course of 161 untreated and tenofovir-treated chronic hepatitis B pregnant patients in a low hepatitis B virus endemic region. J Viral Hepat 2016; 23:15-22. [PMID: 26192022 DOI: 10.1111/jvh.12436] [Citation(s) in RCA: 39] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/04/2015] [Accepted: 06/01/2015] [Indexed: 12/11/2022]
Abstract
Hepatitis B immunoprophylaxis failure is linked to high maternal viraemia. There is limited North American data on hepatitis B outcomes in pregnancy. Pregnant hepatitis B carriers were enrolled January 2011-December 2014 and offered tenofovir in the 3rd trimester if hepatitis B virus (HBV)-DNA was >7-log IU/mL. Outcomes were determined in treated vs untreated patients. In total, 161 women with 169 pregnancies (one twin, 170 infants; median age 32 years), 18% (29/161) HBeAg+ and median HBV-DNA 2.51 log IU/mL (IQR 1.66-3.65; range 0.8-8.1) were studied. 14.3% (23/161) received tenofovir due to high viral load (16/23, median 74 days, IQR 59-110) or due to liver disease (7/23). In 10/16 treated due to high viraemia, with confirmed adherence, follow-up HBV-DNA showed a 5.49 log decline (P = 0.003). In treatment naïve mothers, median alanine aminotransferase (ALT) increased from 17 IU/L (IQR 12-24) to 29 (IQR 18-36) post-partum (P = 1.5e-7). In seven highly viraemic mothers who declined therapy (HBV-DNA >8-log IU/mL); median ALT increased ~3X from baseline (P < 0.01). 26% (44/169) had Caesarean section with no difference in treated vs untreated subjects. No tenofovir-treated mothers had renal dysfunction. Data were available on 167/170 infants; in 50.8% (85/167) who completed immunoprophylaxis, 98.8% (84/85, including 12 exposed to tenofovir in utero) were HBV immune. One infant born to an HBeAg+ mother with HBV-DNA >8-log IU/mL failed immunoprophylaxis. In this prospective Canadian cohort study, most untreated mothers experienced mild HBV flares. Tenofovir in pregnancy is well tolerated and reduces viral load prior to parturition.
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Affiliation(s)
- G Samadi Kochaksaraei
- Calgary Liver Unit, Division of Gastroenterology and Hepatology, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
| | - E Castillo
- Medical Disorders in Pregnancy, Division of Internal Medicine, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
| | - M Osman
- Alberta Health, Government of Alberta, Edmonton, AB, Canada
| | - K Simmonds
- Alberta Health, Government of Alberta, Edmonton, AB, Canada
| | - A N Scott
- Alberta Health, Government of Alberta, Edmonton, AB, Canada
| | - J I Oshiomogho
- Calgary Liver Unit, Division of Gastroenterology and Hepatology, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
| | - S S Lee
- Calgary Liver Unit, Division of Gastroenterology and Hepatology, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
| | - R P Myers
- Calgary Liver Unit, Division of Gastroenterology and Hepatology, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
| | - S R Martin
- Department of Paediatrics, Alberta Children's Hospital, Calgary, AB, Canada
| | - C S Coffin
- Calgary Liver Unit, Division of Gastroenterology and Hepatology, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
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Tekin Koruk S, Batirel A, Kose S, Cetin Akhan S, Aygen B, Tulek N, Hatipoglu Ç, Bulut C, Yıldız O, Sacligil C, Sirmatel F, Altunok E. Evaluation of hepatitis B virus transmission and antiviral therapy among hepatitis B surface antigen-positive pregnant women. J Obstet Gynaecol Res 2015; 41:1870-6. [PMID: 26369498 DOI: 10.1111/jog.12821] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2015] [Accepted: 06/25/2015] [Indexed: 12/21/2022]
Abstract
AIM The aim of the present study was to assess the potential risk of hepatitis B virus (HBV) vertical transmission among Turkish parturient women and to evaluate the efficacy and safety of antiviral agents. MATERIAL AND METHODS Data were collected retrospectively from 114 HBV-infected pregnant women and their infants in eight health institutions in Turkey. RESULTS The baseline characteristics of the women were: mean age, 28.3 ± 5.2 years; alanine aminotransferase, 57.4 ± 139.0 U/L; aspartate aminotransferase, 56.6 ± 150.0 U/L; and HBV DNA, 8.3 × 10(7) ± 2.6 × 10(8) copies/mL. Family history of HBV infection was detected in 53.5% (n = 61). In total, 60 (52.6%) pregnant women received tenofovir (60.0%), lamivudine (33.3%) or telbivudine (6.7%) therapy at the median gestational age of 22.2 ± 8.5 (1-36) weeks. All infants were vaccinated and hepatitis B immune globulin was administered, with 81 of them (71.1%) available for follow-up. After completion of HBV vaccination course, 71 (87.7%) infants had protective anti-HBs levels, three (3.7%) were hepatitis B surface antigen-positive, and seven (8.6%) were hepatitis B surface antigen-negative with nonprotective anti-HBs levels. Five of the infants had low gestational birthweight but no other birth defects were observed. CONCLUSION According to our results, viral load may not be the only effecting factor for transmission of HBV to children of infected mothers. Pregnant women with high viral load should be followed-up closely during pregnancy. They should begin to take tenofovir or telbivudine, which are category B drugs for pregnancy, at the beginning of the third trimester at the latest. We need new treatment strategies; and close follow-up of mothers and children is another important issue.
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Affiliation(s)
- Suda Tekin Koruk
- Department of Infectious Diseases and Clinical Microbiology, Faculty of Medicine, Harran University, Sanliurfa, Turkey
| | - Ayse Batirel
- Department of Infectious Diseases and Clinical Microbiology, Kartal Dr. Lutfi Kirdar Training and Research Hospital, Istanbul, Turkey
| | - Sukran Kose
- Department of Infectious Diseases and Clinical Microbiology, Izmir Tepecik Training and Research Hospital, Izmir, Turkey
| | - Sila Cetin Akhan
- Department of Infectious Diseases and Clinical Microbiology, Kocaeli University Faculty of Medicine, Kocaeli, Turkey
| | - Bilgehan Aygen
- Department of Infectious Diseases and Clinical Microbiology, Faculty of Medicine, Erciyes University, Kayseri, Turkey
| | - Necla Tulek
- Department of Infectious Diseases and Clinical Microbiology, Ankara Training and Research Hospital, Ankara, Turkey
| | - Çigdem Hatipoglu
- Department of Infectious Diseases and Clinical Microbiology, Ankara Training and Research Hospital, Ankara, Turkey
| | - Cemal Bulut
- Department of Infectious Diseases and Clinical Microbiology, Ankara Training and Research Hospital, Ankara, Turkey
| | - Orhan Yıldız
- Department of Infectious Diseases and Clinical Microbiology, Faculty of Medicine, Erciyes University, Kayseri, Turkey
| | - Cahide Sacligil
- Department of Infectious Diseases and Clinical Microbiology, Kartal Yavuz Selim Training and Research Hospital, Istanbul, Turkey
| | - Fatma Sirmatel
- Department of Infectious Diseases and Clinical Microbiology, Faculty of Medicine, Abant Izzet Baysal University, Bolu, Turkey
| | - Elif Altunok
- Department of Infectious Diseases and Clinical Microbiology, Kocaeli University Faculty of Medicine, Kocaeli, Turkey
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Abstract
The screening for HBsAg is a medical obligation in France during pregnancy. A serovaccination with antiHBs immunoglobulins (100 IU) and a 1st dose of vaccine (10 μg) has to be realized during the first 12 hours of life when the mother is HBsAg+. The serovaccination failures are related to high maternal viral load (HBV-DNA>7 log IU/mL). In this case, a treatment with analogue (tenofovir) associated with serovaccination could be performed during the last trimester of pregnancy. The risk of mother-to-child transmission of virus C is around 3 to 5% in case of HCV-RNA positive without co-infection with HIV. The mode of delivery is unchanged in case of maternal HBV or HCV. Breast-feeding is not contra-indicated in case of maternal HBV or HCV infection.
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Affiliation(s)
- Philippe Sogni
- Université Paris-Descartes, Sorbonne Paris Cité, France; AP-HP, hôpital Cochin, service d'hépatologie, 27, rue du Faubourg-Saint-Jacques, 75679 Paris cedex 14, France.
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Lamberth JR, Reddy SC, Pan JJ, Dasher KJ. Chronic hepatitis B infection in pregnancy. World J Hepatol 2015; 7:1233-7. [PMID: 26019737 PMCID: PMC4438496 DOI: 10.4254/wjh.v7.i9.1233] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/29/2014] [Revised: 01/26/2015] [Accepted: 02/10/2015] [Indexed: 02/06/2023] Open
Abstract
There are no standard guidelines to follow when a patient with chronic hepatitis B infection becomes pregnant or desires pregnancy. Topics to consider include which patients to treat, when to start treatment, what treatment to use and when to stop treatment. Without any prophylaxis or antiviral therapy, a hepatitis B surface antigen and E antigen positive mother has up to a 90% likelihood of vertical transmission of hepatitis B virus (HBV) to child. Standard of care in the United States to prevent perinatal transmission consists of administration of hepatitis B immune globulin and HBV vaccination to the infant. The two strongest risk factors of mother to child transmission (MTCT) of HBV infection despite immunoprophylaxis are high maternal HBV viral load and high activity of viral replication. The goal is to prevent transmission of HBV at birth by decreasing viral load and/or decreasing activity of the virus. Although it is still somewhat controversial, most evidence shows that starting antivirals in the third trimester is effective in decreasing MTCT without affecting fetal development. There is a growing body of literature supporting the safety and efficacy of antiviral therapies to reduce MTCT of hepatitis B. There are no formal recommendations regarding which agent to choose. Tenofovir, lamivudine and telbivudine have all been proven efficacious in decreasing viral load at birth without known birth defects, but final decision of which antiviral medication to use will have to be determined by physician and patient. The antivirals may be discontinued immediately if patient is breastfeeding, or within first four weeks if infant is being formula fed.
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Affiliation(s)
- Jennifer R Lamberth
- Jennifer R Lamberth, Sheila C Reddy, Jen-Jung Pan, Kevin J Dasher, Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, the University of Texas Health Science Center at Houston, Houston, TX 77030, United States
| | - Sheila C Reddy
- Jennifer R Lamberth, Sheila C Reddy, Jen-Jung Pan, Kevin J Dasher, Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, the University of Texas Health Science Center at Houston, Houston, TX 77030, United States
| | - Jen-Jung Pan
- Jennifer R Lamberth, Sheila C Reddy, Jen-Jung Pan, Kevin J Dasher, Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, the University of Texas Health Science Center at Houston, Houston, TX 77030, United States
| | - Kevin J Dasher
- Jennifer R Lamberth, Sheila C Reddy, Jen-Jung Pan, Kevin J Dasher, Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, the University of Texas Health Science Center at Houston, Houston, TX 77030, United States
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Bacq Y, Gaudy-Graffin C, Marchand S. [Prophylaxis of mother-to-infant transmission of hepatitis B virus]. Arch Pediatr 2015; 22:427-34. [PMID: 25725975 DOI: 10.1016/j.arcped.2014.12.017] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2014] [Revised: 09/19/2014] [Accepted: 12/28/2014] [Indexed: 02/07/2023]
Abstract
Hepatitis B virus (HBV) infection is a worldwide health problem and mother-to-infant (or vertical) transmission is the main source of chronic infection in Asian countries. Administration of HBV vaccine to the infant at birth, with or without concurrent specific immunoglobulin, efficiently prevents such transmission (efficacy>90%). In France, testing Ag HBs is mandatory during pregnancy in all pregnant women. Infants born to Ag HBs-positive mothers should receive the first injection of vaccine and one injection of specific immunoglobulins at birth. Vaccination should thereafter be completed according to a three-injection protocol (at 1 and 6 months) or a four-injection protocol in case of prematurity. Failure of immunoprophylaxis can be observed when the viral load is very high in the mother during pregnancy (HBV-DNA levels>200,000 IU/mL). In such women, antiviral therapy with analogs (lamivudine, telbivudine, or tenofovir) during the third trimester of pregnancy and 1 month post-partum, in association with accurate immunoprophylaxis, may prevent vertical transmission. The optimal cut-off value of maternal viral load for antiviral therapy in late pregnancy and post-partum to prevent vertical transmission is still under debate.
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Affiliation(s)
- Y Bacq
- Service d'hépatogastroentérologie, hôpital Trousseau, CHRU de Tours, 37044 Tours cedex, France.
| | - C Gaudy-Graffin
- Inserm U966, faculté de médecine, université François-Rabelais, 37044 Tours cedex, France; Service de bactériologie et virologie, hôpital Bretonneau, CHRU de Tours, 37044 Tours cedex, France
| | - S Marchand
- Service de médecine pédiatrique, hôpital Clocheville, CHRU de Tours, 37044 Tours cedex, France
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Cholongitas E, Tziomalos K, Pipili C. Management of patients with hepatitis B in special populations. World J Gastroenterol 2015; 21:1738-1748. [PMID: 25684938 PMCID: PMC4323449 DOI: 10.3748/wjg.v21.i6.1738] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/08/2014] [Revised: 10/27/2014] [Accepted: 11/19/2014] [Indexed: 02/06/2023] Open
Abstract
The development of effective nucleos(t)ide analogs (NAs) against hepatitis B virus (HBV) has improved the outcome of patients with chronic hepatitis B (CHB). This review updates issues related to the management of CHB patients included in special populations. Entecavir (ETV) and tenofovir (TDF) represent the currently recommended first-line NAs in patients with HBV decompensated cirrhosis. The combination of HBV immunoglobulin (usually for a finite duration) and NA is considered the standard of care for prophylaxis against HBV recurrence after liver transplantation. TDF is the best choice for hemodialysis patients and in patients with chronic kidney disease with nucleoside resistance. ETV and telbivudine are the preferred options in naïve renal transplant recipients and with low viremia levels, respectively. All hepatitis B surface antigen (HBsAg)-positive candidates should be treated with NAs before renal transplantation to achieve undetectable HBV DNA at the time of transplantation. Conventional interferon or NAs can also be used in children, on the basis of well-established therapeutic indication. Pregnant women at high risk of perinatal transmission could be treated with lamivudine, telbivudine or TDF in the last trimester of pregnancy. HBsAg-positive patients under immunosuppression should receive NA pre-emptively (regardless of HBV DNA levels) up to 12 mo after its cessation. In HBsAg negative, anti-HBc positive patients under immunosuppression, further studies are needed to form a final conclusion; however, it seems that anti-HBV prophylaxis is justified in such patients with hematological diseases and/or for those receiving rituximab-containing regimens, regardless of their anti-HBs or serum HBV DNA status.
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Guettrot-Imbert G, Plessier A, Hillaire S, Delluc C, Leroux G, Le Guern V, Costedoat-Chalumeau N. [Liver diseases and pregnancy]. Rev Med Interne 2015; 36:211-8. [PMID: 25591870 DOI: 10.1016/j.revmed.2014.10.355] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2014] [Accepted: 10/20/2014] [Indexed: 12/15/2022]
Abstract
Liver disease can be observed in pregnant women whether or not related to pregnancy. Liver disorders can be revealed by pruritus, vomiting, jaundice or abnormal liver blood tests during pregnancy. These liver manifestations can lead to the diagnosis of liver disease specifically associated to pregnancy as intrahepatic pregnancy, intrahepatic cholestasis of pregnancy, Hyperemesis gravidarum, acute fatty liver of pregnancy and preeclampsia-induced liver injury. Pregnancy may also be a risk factor for other liver diseases coincident with pregnancy as viral hepatitis, thrombosis, drug toxicity or gallstone. Finally, pre-existing liver disease must be taken into account given the risk of fœto-maternal transmission risk as well as the risk of decompensation of underlying cirrhosis secondary to the hemodynamic changes caused by pregnancy. The aim of this revue is to perform an update on the various situations that can be observed, the principles of management of these liver diseases, in order to reduce the risk of complications and to ensure the best maternal and fetal prognosis.
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Affiliation(s)
- G Guettrot-Imbert
- Service de médecine interne, hôpital Gabriel-Montpied, CHU de Clermont-Ferrand, 58, rue Montalembert, 63003 Clermont-Ferrand cedex 1, France
| | - A Plessier
- Service d'hépatologie, institut national de la santé et de la recherche médicale U773, université Denis Diderot-Paris 7, hôpital Beaujon, AP-HP, 92210 Clichy, France
| | - S Hillaire
- Service d'hépatologie, institut national de la santé et de la recherche médicale U773, université Denis Diderot-Paris 7, hôpital Beaujon, AP-HP, 92210 Clichy, France; Service de médecine interne, hôpital Foch, 92150 Suresnes, France
| | - C Delluc
- EA 3878 (GETBO), université de Bretagne Occidentale, 29238 Brest, France
| | - G Leroux
- Service de médecine interne 1, AP-HP, groupe hospitalier Pitié-Salpêtrière, 75651 Paris, France
| | - V Le Guern
- Centre de référence maladies auto-immunes et systémiques rares, service de médecine interne, université René-Descartes, pôle médecine, hôpital Cochin, AP-HP, 27, rue du Faubourg-Saint-Jacques, 75679 Paris cedex 14, France
| | - N Costedoat-Chalumeau
- Centre de référence maladies auto-immunes et systémiques rares, service de médecine interne, université René-Descartes, pôle médecine, hôpital Cochin, AP-HP, 27, rue du Faubourg-Saint-Jacques, 75679 Paris cedex 14, France.
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Jackson V, Ferguson W, Kelleher TB, Lawless M, Eogan M, Nusgen U, Coughlan S, Connell J, Lambert JS. Lamivudine treatment and outcome in pregnant women with high hepatitis B viral loads. Eur J Clin Microbiol Infect Dis 2014; 34:619-23. [PMID: 25381607 DOI: 10.1007/s10096-014-2270-0] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2014] [Accepted: 10/20/2014] [Indexed: 01/27/2023]
Abstract
Perinatal transmission is the most common mode of hepatitis B virus (HBV) transmission and is a leading cause of chronic infection worldwide. Maternal treatment with lamivudine (LAM) can result in a rapid and significant reduction in HBV viral load (VL) and, thus, mitigate the risk of mother-to-child transmission (MTCT). The aim of this study was to retrospectively evaluate the safety of LAM treatment administered in the third trimester of pregnancy and determine the influence, if any, on infant outcome. The medical charts of all HBV surface antigen (HBsAg)-positive women eligible for treatment with LAM and who registered for antenatal care between 2007 and 2012 were retrospectively reviewed. During the 6-year period, 45 women met the criteria for LAM treatment. Thirty-six women (80 %) accepted treatment; the remaining women declined treatment (5), defaulted from care (3) or transferred to another maternity unit (1). The median duration of treatment was 11.4 weeks (range 5.3-17.4) and the median baseline VL was 1.4 × 10(8) IU/mL (range 1.8 × 10(7)-1.7 × 10(8)). The median VL at delivery was 2.3 × 10(5) IU/mL and 60 % of women achieved a VL reduction >2 log10 IU/mL before delivery. No cases of perinatal transmission occurred in the infants born to mothers who received treatment; however, one infant, born to a mother who defaulted from care, was HBV-infected at 8 months. The results suggest that LAM therapy in highly viraemic HBV-infected pregnant women could lower the rate of vertical transmission.
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Affiliation(s)
- V Jackson
- Department of Infectious Diseases, The Rotunda Hospital, Dublin, Ireland
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49
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Efficacy and safety of tenofovir disoproxil fumarate in pregnancy to prevent perinatal transmission of hepatitis B virus. J Hepatol 2014; 61:502-7. [PMID: 24801414 DOI: 10.1016/j.jhep.2014.04.038] [Citation(s) in RCA: 130] [Impact Index Per Article: 11.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/20/2014] [Revised: 04/02/2014] [Accepted: 04/24/2014] [Indexed: 12/21/2022]
Abstract
BACKGROUND & AIMS Perinatal transmission of hepatitis B virus still occurs despite immunoprophylaxis in approximately 9% of children from highly viraemic mothers. Antiviral therapy in this setting has been suggested, however with limited evidence to direct agent choice. METHODS We conducted a multi-centre, prospective, opt-in observational study of antiviral safety and efficacy in pregnant women with high viral load (>7 log IU/ml); lamivudine was used from 2007 to 2010 and tenofovir disoproxil fumarate (TDF) from late 2010. Outcomes of treated and untreated cohorts were compared. RESULTS 120 women with 130 pregnancies used TDF (58), lamivudine (52 including four who switched due to TDF intolerance) and no therapy (20). 96% were HBeAg positive, with baseline viral load mean 7.8 log IU/ml (±0.72) and ALT median 25 U/L (18.75-33). Duration of antiviral theraphy before birth was mean 58 days (±19) TDF and 53 (±14) lamivudine. Viral load declined by 3.64 log IU/ml (±0.9) TDF and 2.81 log IU/ml (±1.33) lamivudine. Virologic failure (birth viral load >7 IU/ml) occurred in 3% and 18% respectively. Congenital abnormality rate and neonatal growth centiles were similar across cohorts. Perinatal transmission reduced significantly to 2% and 0% in TDF and lamivudine cohorts, compared with 20% in untreated. CONCLUSIONS TDF in this setting is safe, effective and more potent than lamivudine. Antiviral therapy did not adversely impact obstetric or infant parameters. More TDF intolerance occurred than expected. Perinatal transmission was significantly reduced in antiviral therapy cohorts.
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Vallet-Pichard A, Pol S. Hepatitis B virus treatment beyond the guidelines: special populations and consideration of treatment withdrawal. Therap Adv Gastroenterol 2014; 7:148-55. [PMID: 25057295 PMCID: PMC4107707 DOI: 10.1177/1756283x14524614] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023] Open
Abstract
The goal of chronic hepatitis B (CHB) treatment is to improve survival by preventing disease progression to decompensated cirrhosis and hepatocellular carcinoma which is the cause of over 1 million deaths annually. The risk of disease progression is reduced when a sustained reduction of hepatitis B virus (HBV) DNA to undetectable levels and suppression of HBV replication are obtained which can result in regression of liver fibrosis and may even reverse cirrhosis. However, even if HBsAg loss occurs, HBV is not completely eradicated by treatment, and long-term therapy is required in patients who are HBeAg(-) and HBeAg(+) who do not maintain off-treatment virological suppression and in those with advanced liver disease. The recently updated European Association of the Study of the Liver (EASL) clinical practical guidelines for HBV have clarified, first, how to treat HBV (interferon or the most potent oral drugs with optimal resistance profiles, i.e. entecavir and tenofovir disoproxil fumarate, should be used as first-line monotherapies); second, who should be treated (CHB in patients with significant liver disease but also patients who are HBsAg(+) and are receiving immunosuppressive treatment, patients coinfected with HBV and human immunodeficiency virus, mothers who are HBsAg(+) with high viral load in late pregnancy associated with sero vaccination to reduce the risk of vertical transmission of HBV; and third, when to stop antiviral therapies. The aim of this review was to clarify how to treat HBV and who should be treated, as well as when to stop treatment. Although the answer to these questions is clear for pegylated interferon, it is more debatable for nucleos(t)ide analogues (anti-HBe seroconversion, HBsAg loss or anti-HBs seroconversion with undetectable HBV DNA are clear indications to discontinue treatment but sustained undetectable HBV DNA in patients who are anti-HBe(+) without significant fibrosis might be another indication).
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Affiliation(s)
- Anais Vallet-Pichard
- Institut Cochin, CNRS (UMR 8104), INSERM U-1016, Paris, France,Université Paris Descartes, Sorbonne Paris Cité, Paris, France,Assistance Publique – Hôpitaux de Paris, Service d’Hépatologie, hôpital Cochin, Paris, France
| | - Stanislas Pol
- Département d’Hépatologie, Hôpital Cochin, 27 Rue du Faubourg Saint Jacques, 75679 Paris Cedex 14, France
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