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Zou H, Zhu L, Cao L, Suo S, Zhu Y, Wang Y, Dong J, Han B, Duan Z, Chen Y, Pan CQ. Vertical Transmission in Mothers Taking TAF With Exceptionally High Viral Load. J Viral Hepat 2025; 32:e70000. [PMID: 39953819 DOI: 10.1111/jvh.70000] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/28/2024] [Revised: 01/07/2025] [Accepted: 01/09/2025] [Indexed: 02/17/2025]
Abstract
Published studies on tenofovir alafenamide (TAF) therapy for preventing vertical transmission of hepatitis B virus (HBV) have primarily enrolled mothers with viremic levels of approximately 7 log10 IU/mL. This study aimed to evaluate the efficacy and safety of TAF therapy in preventing mother-to-child transmission (MTCT) in mothers with exceptionally high viral loads, defined as HBV DNA levels > 2,000,000 IU/mL. Hepatitis B e antigen (HBeAg)-positive mothers with HBV DNA levels > 2,000,000 IU/mL were prospectively enrolled from four hospitals and initiated on TAF therapy between gestational weeks 26 and 28, continuing until delivery. All infants received immunoprophylaxis and were followed up to 28 weeks postpartum. The primary endpoints were the MTCT rate and the occurrence of congenital abnormalities in infants. Secondary outcomes included maternal HBV suppression at delivery and the safety of both mothers and infants. Among 137 mothers screened, 120 were enrolled in TAF therapy, and 121 infants completed the study. At delivery, 93.3% (112/120) of mothers achieved HBV DNA levels < 200,000 IU/mL. At birth, 0.8% (1/121) of infants had a congenital malformation, and 9.9% (12/121) tested positive for HBsAg. The vertical transmission rate was 2% (2/121, intention-to-treat) at 28 weeks of age. No severe adverse effects were reported in mothers or infants. On-treatment and postpartum alanine aminotransferase (ALT) flares after TAF cessation occurred in 7.5% (9/120) and 41.1% (46/112) of mothers, respectively, alongside viral rebound after cessation. Infant physical development remained within normal ranges based on national reference standards. In summary, approximately 2% of mothers on TAF therapy during late pregnancy experienced MTCT, despite proper immunoprophylaxis for their infants. Extending the treatment duration beyond 12 weeks for mothers with extremely high viral loads is recommended to improve MTCT prevention. No safety concerns were observed for either mothers or infants. Trial Registration: ClinicalTrials.gov identifier: NCT04237376.
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Affiliation(s)
- Huaibin Zou
- Fourth Department of Liver Disease, Beijing Youan Hospital, Capital Medical University, Beijing, China
| | - Liying Zhu
- Department of Infectious Disease, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Lihua Cao
- Liver Disease Center, Qinhuangdao Third Hospital, Qinhuangdao, China
| | - Shuyi Suo
- Department of Obstetrics and Gynecology, Tongliao Infectious Diseases Hospital, Tongliao, China
| | - Yunxia Zhu
- Department of Obstetrics and Gynecology, Beijing Youan Hospital, Capital Medical University, Beijing, China
| | - Yuanyuan Wang
- Department of Infectious Disease, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Jingchao Dong
- Liver Disease Center, Qinhuangdao Third Hospital, Qinhuangdao, China
| | - Baiyila Han
- Tongliao Infectious Diseases Hospital, Tongliao, China
| | - Zhongping Duan
- Fourth Department of Liver Disease, Beijing Youan Hospital, Capital Medical University, Beijing, China
| | - Yu Chen
- Fourth Department of Liver Disease, Beijing Youan Hospital, Capital Medical University, Beijing, China
| | - Calvin Q Pan
- Division of Gastroenterology and Hepatology, Department of Medicine, NYU Langone Health, NYU School of Medicine, Flushing, New York, USA
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Forna L, Lupu A, Bozomitu L, Paduraru G, Cojocariu C, Anton C, Girleanu I, Muzica CM, Trifan A. Identifying Childhood Risk Factors for Hepatitis B with a Focus on Vertical Transmission. Diseases 2024; 12:215. [PMID: 39329884 PMCID: PMC11431014 DOI: 10.3390/diseases12090215] [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: 07/10/2024] [Revised: 09/12/2024] [Accepted: 09/14/2024] [Indexed: 09/28/2024] Open
Abstract
BACKGROUND Despite worldwide vaccination efforts, Hepatitis B virus (HBV) infection remains a significant global health burden, particularly in regions where vertical transmission is prevalent. Given Romania's history as an endemic area for hepatitis B from the 1990s until the early 2000s and the previously high infection rates among children, it is crucial to continually evaluate HBV infection in this population to monitor current trends, assess the long-term impact of vaccination programs, and address any remaining gaps in prevention and treatment efforts. This study aims to identify childhood risk factors associated with HBV acquisition, examining the role of maternal HBV status in child HBV infection, focusing on vertical transmission among a cohort of 654 children, with maternal infection as the independent variable and child infection as the dependent variable. METHODS We assessed potential risk factors and vaccination coverage among these children. The cohort included 148 children who tested positive for chronic hepatitis B from those 654 tested for HBsAg. Anamnestic data and vaccination history were analyzed, with particular attention to birth type and surgical interventions. RESULTS Of the 148 HBV-positive children, 80.4% were delivered naturally. Among these, 130 had received hepatitis B vaccination, and 5 were also given hepatitis B immunoglobulin at birth, 4 of whom were born via cesarean section. In the control group, comprising 418 vaccinated children, a lesser proportion were unvaccinated (2.2%). Documented surgical interventions included general and dental surgeries, as well as a single blood transfusion. CONCLUSIONS The study emphasizes the need for comprehensive vaccination strategies and illuminates potential correlations between birth type and vaccination status with childhood HBV infection. Crucially, it highlights the necessity of diligent monitoring and treatment of pregnant women with HBV to prevent vertical transmission as effectively as possible.
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Affiliation(s)
- Lorenza Forna
- Pediatrics—“Sf. Maria” Clinical Emergency Children’s Hospital, Iassy 700309, Romania; (L.F.); (A.L.); (G.P.)
- Faculty of General Medicine, University of Medicine and Pharmacy “Gr. T. Popa”, Iași 700115, Romania; (C.C.); (C.A.); (I.G.); (C.M.M.); (A.T.)
| | - Ancuta Lupu
- Pediatrics—“Sf. Maria” Clinical Emergency Children’s Hospital, Iassy 700309, Romania; (L.F.); (A.L.); (G.P.)
- Faculty of General Medicine, University of Medicine and Pharmacy “Gr. T. Popa”, Iași 700115, Romania; (C.C.); (C.A.); (I.G.); (C.M.M.); (A.T.)
| | - Laura Bozomitu
- Pediatrics—“Sf. Maria” Clinical Emergency Children’s Hospital, Iassy 700309, Romania; (L.F.); (A.L.); (G.P.)
- Faculty of General Medicine, University of Medicine and Pharmacy “Gr. T. Popa”, Iași 700115, Romania; (C.C.); (C.A.); (I.G.); (C.M.M.); (A.T.)
| | - Gabriela Paduraru
- Pediatrics—“Sf. Maria” Clinical Emergency Children’s Hospital, Iassy 700309, Romania; (L.F.); (A.L.); (G.P.)
- Faculty of General Medicine, University of Medicine and Pharmacy “Gr. T. Popa”, Iași 700115, Romania; (C.C.); (C.A.); (I.G.); (C.M.M.); (A.T.)
| | - Camelia Cojocariu
- Faculty of General Medicine, University of Medicine and Pharmacy “Gr. T. Popa”, Iași 700115, Romania; (C.C.); (C.A.); (I.G.); (C.M.M.); (A.T.)
- Department of Clinical Gastroenterology, “Sf. Spiridon” Clinical Emergency Hospital, Iași 700111, Romania
| | - Carmen Anton
- Faculty of General Medicine, University of Medicine and Pharmacy “Gr. T. Popa”, Iași 700115, Romania; (C.C.); (C.A.); (I.G.); (C.M.M.); (A.T.)
- Department of Clinical Gastroenterology, “Sf. Spiridon” Clinical Emergency Hospital, Iași 700111, Romania
| | - Irina Girleanu
- Faculty of General Medicine, University of Medicine and Pharmacy “Gr. T. Popa”, Iași 700115, Romania; (C.C.); (C.A.); (I.G.); (C.M.M.); (A.T.)
- Department of Clinical Gastroenterology, “Sf. Spiridon” Clinical Emergency Hospital, Iași 700111, Romania
| | - Cristina Maria Muzica
- Faculty of General Medicine, University of Medicine and Pharmacy “Gr. T. Popa”, Iași 700115, Romania; (C.C.); (C.A.); (I.G.); (C.M.M.); (A.T.)
- Department of Clinical Gastroenterology, “Sf. Spiridon” Clinical Emergency Hospital, Iași 700111, Romania
| | - Anca Trifan
- Faculty of General Medicine, University of Medicine and Pharmacy “Gr. T. Popa”, Iași 700115, Romania; (C.C.); (C.A.); (I.G.); (C.M.M.); (A.T.)
- Department of Clinical Gastroenterology, “Sf. Spiridon” Clinical Emergency Hospital, Iași 700111, Romania
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di Filippo Villa D, Navas MC. Vertical Transmission of Hepatitis B Virus-An Update. Microorganisms 2023; 11:1140. [PMID: 37317114 DOI: 10.3390/microorganisms11051140] [Citation(s) in RCA: 16] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2023] [Revised: 03/26/2023] [Accepted: 03/28/2023] [Indexed: 06/16/2023] Open
Abstract
Hepatitis B virus (HBV) infection is a major public health problem in the world. Approximately 296 million people are chronically infected. In endemic areas, vertical transmission is a common route of transmission. There are several strategies for the prevention of HBV vertical transmission, such as antiviral treatment during the third trimester of pregnancy and immunoprophylaxis to newborns that includes the administration of hepatitis B immune globulin (HBIG) and an HBV vaccine. Despite this, immunoprophylaxis failure can occur in up to 30% of infants born to HBeAg-positive mothers and/or with high viral load. Therefore, management and prevention of HBV vertical transmission is of paramount significance. In this article, we provided a review of the epidemiology, mechanisms of pathogenesis and risk factors of vertical transmission, as well as the strategies implemented to prevent the infection.
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Affiliation(s)
- Diana di Filippo Villa
- Gastrohepatology Group, Faculty of Medicine, Universidad de Antioquia (UdeA), Calle 70 No. 52-21, Medellin 050010, Colombia
| | - Maria-Cristina Navas
- Gastrohepatology Group, Faculty of Medicine, Universidad de Antioquia (UdeA), Calle 70 No. 52-21, Medellin 050010, Colombia
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The Use of Tenofovir Disoproxil Fumarate and Tenofovir Alafenamide for Preventing Vertical Transmission of Hepatitis B. J Clin Gastroenterol 2023; 57:127-138. [PMID: 36598804 DOI: 10.1097/mcg.0000000000001785] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Abstract
BACKGROUND Mother-to-child transmission (MTCT) of hepatitis B virus may occur in highly viremic mothers despite the infants receiving appropriate immunoprophylaxis. We aimed to review tenofovir disoproxil fumarate (TDF) and tenofovir alafenamide (TAF) data for preventing MTCT. METHODS AND DATA SELECTION We performed a systematic review between January 1, 2015 and December 31, 2021 on PUBMED, EMBASE, Cochrane, CNKI, and Wanfang databases. Data was extracted from randomized controlled trials or cohort studies in English or Chinese. The outcomes of interest included the efficacy and safety of TDF versus TAF or TDF/TAF versus placebo for preventing MTCT (PROSPERO registration: CRD42021256656). RESULTS Data from forty-three studies (13 randomized controlled trials, 30 nonrandomized studies) were included in the review. All infants in the studies received appropriate immunoprophylaxis. Among 3656 highly viremic mothers treated with TDF, hepatitis B virus DNA suppression to the levels <200,000 IU/mL at delivery was achieved in 34% to 100% of mothers. MTCT rates were 0 to 5% and 2 to 83% in mothers treated with TDF and in those who received no treatment, respectively. Congenital malformation rates were 0 to 2.1% in the TDF groups, which did not differ from the nontreated groups. Similar findings were reported in 4 studies that enrolled 326 mothers for maternal TAF therapy, resulting in 0% of MTCT and 0% infant malformation. All studies observed that TDF or TAF maternal therapy reduced MTCT rates significantly without safety concerns when compared with untreated groups, except for 1 RCT that failed the therapeutic endpoint. CONCLUSIONS TDF is well established for preventing MTCT in highly viremic mothers, whereas TAF may become an option as data emerges.
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Kiweewa FM, Tierney C, Butler K, Peters MG, Vhembo T, Moodley D, Govender V, Mohtashemi N, Ship H, Musoke P, Dula D, George K, Chakhtoura N, Fowler MG, Currier JS, Bhattacharya D. Brief Report: Impact of Antiretroviral Regimen on Pregnancy and Infant Outcomes in Women With HIV/ HBV Coinfection. J Acquir Immune Defic Syndr 2022; 91:79-84. [PMID: 35621877 PMCID: PMC9377493 DOI: 10.1097/qai.0000000000003022] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2021] [Accepted: 04/28/2022] [Indexed: 11/26/2022]
Abstract
BACKGROUND There are limited data on the impact of antenatal antiretroviral regimens (ARV) on pregnancy and infant outcomes in HIV/HBV coinfection. We compared outcomes among 3 antenatal antiretroviral regimens for pregnant women with HIV/HBV. METHODS The PROMISE study enrolled ARV-naive pregnant women with HIV. Women with HBV were randomized to (no anti-HBV)-zidovudine (ZDV) + intrapartum nevirapine and 1 week of tenofovir disoproxil fumarate and emtricitabine (TDF-FTC); (3TC)-3TC + ZDV + LPV/r; or (FTC-TDF)-FTC + TDF + LPV/r. Pairwise group comparisons were performed with Fisher exact, t , or log rank tests. Adverse pregnancy outcome (APO) was a composite of low birth weight, preterm delivery, spontaneous abortion, stillbirth, or congenital anomaly. RESULTS Of 138 women with HIV/HBV, 42, 48, and 48 were analyzed in the no anti-HBV, 3TC, and FTC-TDF arms. Median age was 27 years. APOs trended lower in the no anti-HBV (26%) vs 3TC (38%), and FTC-TDF arms (35%), P ≥ 0.25). More infant deaths occurred among the FTC-TDF [6 (13%)] vs no anti-HBV [2 (5%)] and 3TC [3 (7%)] arms. There were no differences in time-to-death, HIV-free survival, birth or one-year WHO Z-score length-for-age, and head circumference. Hepatitis B e antigen (HBeAg) was associated with an increased risk of APO, 48% vs 27% (odds ratio 2.79, 95% confidence interval: 1.19 to 6.67, post hoc ). CONCLUSION With HBV/HIV coinfection, the risk of an APO was increased with maternal ARV compared with ZDV alone, although the differences were not statistically significant. Maternal HBeAg was associated with a significantly increased risk of APO. Infant mortality was highest with FTC + TDF + LPV/r. Early assessment of HBeAg could assist in identifying high-risk pregnancies for close monitoring.
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Affiliation(s)
- Flavia Matovu Kiweewa
- Makerere University—Johns Hopkins University Research Collaboration, Kampala, Uganda
- Department of Epidemiology and Biostatistics, Makerere University School of Public Health, College of Health Sciences, Kampala, Uganda
| | - Camlin Tierney
- Center for Biostatistics in AIDS Research, Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA
| | - Kevin Butler
- Center for Biostatistics in AIDS Research, Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA
| | - Marion G. Peters
- Department of Medicine, Feinberg School of Medicine, Northwestern University CRS, Chicago, IL
| | - Tichaona Vhembo
- Department of Obstetrics and Gynaecology, University of Zimbabwe College of Health Sciences, Harare, Zimbabwe
| | - Dhayendre Moodley
- Department of Obstetrics and Gynaecology, University of KwaZulu-Natal, Nelson Mandela School of Medicine, Durban, South Africa
| | - Vani Govender
- Centre for the AIDS Programme of Research in South Africa, Congella, South Africa
| | - Neaka Mohtashemi
- Department of Medicine, Division of Infectious Diseases, David Geffen School of Medicine, University of California, Los Angeles, CA
| | - Hannah Ship
- University of Miami Miller School of Medicine, Miami, FL
| | - Philippa Musoke
- Makerere University—Johns Hopkins University Research Collaboration, Kampala, Uganda
- Department of Paediatrics and Child Health, College of Health Sciences, Makerere University
| | - Dingase Dula
- Centre for AIDS Research in South Africa and Department of Obstetrics and Gynecology, School of Clinical Medicine, University of KwaZulu Natal, Durban, South Africa
| | | | - Nahida Chakhtoura
- National Institutes of Health (NIH), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), Bethesda, MD; and
| | - Mary G. Fowler
- Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD
| | - Judith S. Currier
- Department of Medicine, Division of Infectious Diseases, David Geffen School of Medicine, University of California, Los Angeles, CA
| | - Debika Bhattacharya
- Department of Medicine, Division of Infectious Diseases, David Geffen School of Medicine, University of California, Los Angeles, CA
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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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Pan CQ. The role of tenofovir disoproxil fumarate for preventing vertical transmission of hepatitis B. Antivir Ther 2022; 27:13596535221076640. [DOI: 10.1177/13596535221076640] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
Background Since immunoprophylaxis failure can occur if maternal serum hepatitis B virus (HBV) DNA levels are >200,000 IU/ml, tenofovir disoproxil fumarate (TDF) therapy has been investigated for preventing mother to child transmission (PMTCT). Methods A literature search for maternal TDF therapy for PMTCT between 1/1/2015 and 7/1/21 on PUBMED, EMBASE, Cochrane, CNKI, and Wanfang databases was performed. Data from RCTs in English or Chinese were extracted and reviewed. The outcomes of interest included the efficacy and safety of TDF versus placebo for PMTCT. Results Among 11 RCTs identified from the databases, the risk-of-bias was low. All studies demonstrated that maternal TDF therapy initiated from the second or third trimester for highly viremic chronic hepatitis B mothers is highly effective and safe in the PMTCT of HBV, except one RCT performed in Thailand which showed no therapeutic advantage on TDF treatment versus placebo for PMTCT (0% vs 3% transmission). Recent emerging data suggest that maternal TDF therapy initiated at the 2nd or early 3rd trimester in mothers with HBV DNA >200,000 IU/ml achieved viremic control before delivery. In the 4-year long follow-up study for maternal TDF therapy, there were no impacts on infants’ physical growth, psychological or mental development, and bone mineral density after fetal exposure to TDF. In the light of updated efficacy and safety data from RCTs, an algorithm was proposed. The approaches in resource-limit areas were discussed. Conclusions TDF is safe for both mothers and infants as the preferred therapy for PMTCT in highly viremic mothers. TDF should be initiated at the second or early third trimester in the combination of the appropriate infants’ immunoprophylaxis.
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Affiliation(s)
- Calvin Q Pan
- Beijing Ditan Hospital, Capital Medical University, Beijing, China
- NYU Langone Health, NYU Grossman School of Medicine, New York, NY, USA
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Yi W, Cao X, Zeng Z, Cao W, Zhang Y, Sun F, Wang Y, Wan G, Li M, Xie Y. Developmental consequences of children born from mothers with telbivudine treatment during late pregnancy: A prospective study with 3-year follow-up. Virulence 2021; 12:1527-1537. [PMID: 34120564 PMCID: PMC8205043 DOI: 10.1080/21505594.2021.1936769] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/01/2021] [Revised: 03/25/2021] [Accepted: 05/26/2021] [Indexed: 12/04/2022] Open
Abstract
We prospectively investigated the neurological development in infants born from mothers treated with telbivudine (LdT) in the third trimester for prevention of hepatitis B virus (HBV) mother-to-infant transmission. Mothers with high HBV load were assigned to either the LdT group (n = 81, 600 mg of LdT each day from gestational week 28 to delivery) or the Control group (n = 39, untreated). Their infants were followed for 36 months to assess physical and neurological developments with Gesell Developmental Schedule tools. At 12 months after birth, the mean scores in the LdT group for gross motor, fine motor, adaptive, linguistic, and personal social domains were similar to those in the Control group. At 36 months, infants in the LdT group had higher mean scores for gross motor than the Control group (98.42 ± 9.69 vs. 94.54 ± 7.48, P = 0.03). In the LdT group, the rates of normal development were higher for gross motor (96.30% vs. 82.05% P = 0.01) and lower for adaptive (74.07% vs. 92.31% P = 0.02). Multivariate regression analyses showed that exposure to LdT during pregnancy was independently associated with infant's development in gross motor (OR 6.49, 95% CI 1.37-30.20, P = 0.02) and adaptive (OR 0.18, 95% CI 0.05-0.71, P = 0.01) at 36 months. These results suggest that prenatal LdT exposure might affect neurological development in long-term observation.Abbreviations: LdT: telbivudine; HBV: hepatitis B virus; HBsAg: hepatitis B surface antigen; HBeAg: hepatitis Be antigen; HbsAb: hepatitis B surface antibody; ALT: alanine aminotransferase; NA: nucleoside/nucleotide analog; LAM: lamivudine; MTCT: mother-to-child transmission; GDS: Gesell Developmental Schedule; OR: odds ratio; CI: confidence interval; DQ: developmental quotient; RMB: renminbi; BMI: body mass Index; HBIG: hepatitis B immunoglobulin.
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Affiliation(s)
- Wei Yi
- Department of Gynecology and Obstetrics, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Xiuzhen Cao
- Department of Gynecology and Obstetrics, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Zhan Zeng
- Department of Hepatology Division 2, Peking University Ditan Teaching Hospital, Beijing, China
| | - Weihua Cao
- Department of Hepatology Division 2, Peking University Ditan Teaching Hospital, Beijing, China
| | - Ying Zhang
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Fangfang Sun
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Ying Wang
- Department of Child Health Care, Beijing Children’s Hospital, Capital Medical University, Beijing, China
| | - Gang Wan
- Medical Records and Statistics Room, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Minghui Li
- Department of Hepatology Division 2, Peking University Ditan Teaching Hospital, Beijing, China
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Yao Xie
- Department of Hepatology Division 2, Peking University Ditan Teaching Hospital, Beijing, China
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
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Erturk US, Mete B, Ozaras R, Saltoglu N, Balkan II, Mert A, Kacmaz B, Saglam O, Guney B, Sayman OA, Tabak F. Plasma and Breast Milk Pharmacokinetics of Tenofovir Disoproxil Fumarate in Nursing Mother with Chronic Hepatitis B-Infant Pairs. Antimicrob Agents Chemother 2021; 65:e0111021. [PMID: 34310204 PMCID: PMC8448110 DOI: 10.1128/aac.01110-21] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2021] [Accepted: 07/13/2021] [Indexed: 11/20/2022] Open
Abstract
Tenofovir use is associated with lower risk of mother-to-infant transmission of the virus, and discontinuation of the treatment is not safe. However, the safety of the drug during pregnancy and breastfeeding is not clear. In this study, we aimed to determine the tenofovir concentration in plasma of mother-infant pairs along with breast milk in chronic hepatitis B patients during the lactation period. A total of 11 mother-infant pairs were enrolled in the study. All the mothers received tenofovir disoproxil fumarate (TDF) 245 mg/day for at least 1 month because of chronic hepatitis B infection. Maternal blood, breast milk, and infant blood samples were obtained concomitantly. Tenofovir concentrations were determined by liquid chromatography-tandem mass spectrometry. The median concentrations of tenofovir in maternal plasma and breast milk samples were 88.44 (interquartile range [IQR], 62.47 to 116.17) ng/ml and 6.69 (IQR, 4.88 to 7.03) ng/ml, respectively. Tenofovir concentrations were undetectable (<4 ng/ml) in all of the infant plasma samples. The ratio of tenofovir concentration in breast milk to that in maternal plasma was 0.07. Tenofovir disoproxil fumarate passes through the breast milk in a small amount. Infants had no detectable tenofovir level in their plasma. Our study suggests that tenofovir disoproxil fumarate treatment is safe during the breastfeeding period in chronic hepatitis B patients.
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Affiliation(s)
- U. S. Erturk
- Istanbul University-Cerrahpasa, Cerrahpasa School of Medicine, Department of Infectious Diseases and Clinical Microbiology, Istanbul, Turkey
| | - B. Mete
- Istanbul University-Cerrahpasa, Cerrahpasa School of Medicine, Department of Infectious Diseases and Clinical Microbiology, Istanbul, Turkey
| | - R. Ozaras
- Medilife Health Group, Department of Infectious Diseases, Istanbul, Turkey
| | - N. Saltoglu
- Istanbul University-Cerrahpasa, Cerrahpasa School of Medicine, Department of Infectious Diseases and Clinical Microbiology, Istanbul, Turkey
| | - I. I. Balkan
- Istanbul University-Cerrahpasa, Cerrahpasa School of Medicine, Department of Infectious Diseases and Clinical Microbiology, Istanbul, Turkey
| | - A. Mert
- Istanbul Medipol University, Department of Infectious Diseases and Clinical Microbiology, Istanbul, Turkey
| | - B. Kacmaz
- American Hospital, Department of Infectious Diseases and Clinical Microbiology, Istanbul, Turkey
| | - O. Saglam
- Novagenix Bioanalytical Drug R&D Center, Ankara, Turkey
| | - B. Guney
- Novagenix Bioanalytical Drug R&D Center, Ankara, Turkey
| | - O. A. Sayman
- Istanbul University-Cerrahpasa, Cerrahpasa School of Medicine, Department of Public Health, Istanbul, Turkey
| | - F. Tabak
- Istanbul University-Cerrahpasa, Cerrahpasa School of Medicine, Department of Infectious Diseases and Clinical Microbiology, Istanbul, Turkey
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10
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Bierhoff M, Angkurawaranon C, Rijken MJ, Sriprawa K, Kobphan P, Nosten FN, van Vugt M, McGready R, Devine A. Tenofovir disoproxil fumarate in pregnancy for prevention of mother to child transmission of hepatitis B in a rural setting on the Thailand-Myanmar border: a cost-effectiveness analysis. BMC Pregnancy Childbirth 2021; 21:157. [PMID: 33618698 PMCID: PMC7901182 DOI: 10.1186/s12884-021-03612-z] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2020] [Accepted: 02/02/2021] [Indexed: 01/19/2023] Open
Abstract
BACKGROUND Hepatitis B Virus (HBV) is transmitted from mother to child which can be prevented via birth dose vaccine combined with three follow up hepatitis B vaccines, hepatitis B immunoglobulins (HBIG), and maternal antiviral treatment with Tenofovir Disoproxil Fumarate (TDF). This study evaluates the cost effectiveness of six strategies to prevent perinatal HBV transmission in a resource limited setting (RLS) on the Thailand-Myanmar border. METHODS The cost effectiveness of six strategies was tested by a decision tree model in R. All strategies included birth and follow up vaccinations and compared cost per infection averted against two willingness to pay thresholds: one-half and one gross domestic product (GDP) per capita. Strategies were: 1) Vaccine only, 2) HBIG after rapid diagnostic test (RDT): infants born to HBsAg+ are given HBIG, 3) TDF after RDT: HBsAg+ women are given TDF, 4) TDF after HBeAg test: HBeAg+ women are given TDF, 5) TDF after high HBV DNA: women with HBV DNA > 200,000 are given TDF, 6) HBIG & TDF after high HBV DNA: women with HBV DNA > 200,000 are given TDF and their infants are given HBIG. One-way and probabilistic sensitivity analyses were conducted on the cost-effective strategies. RESULTS Vaccine only was the least costly option with TDF after HBeAg test strategy as the only cost-effective alternative. TDF after HBeAg test had an incremental cost-effectiveness ratio of US$1062; which would not be considered cost-effective with the lower threshold of one-half GDP per capita. The one-way sensitivity analysis demonstrated that the results were reasonably robust to changes in single parameter values. The PSA showed that TDF after HBeAg test had an 84% likelihood of being cost effective at a willingness to pay threshold of one GDP per capita per infection averted. CONCLUSIONS We found that TDF after HBeAg test has the potential to be cost-effective if TDF proves effective locally to prevent perinatal HBV transmission. The cost of TDF treatment and reliability of the RDT could be barriers to implementing this strategy. While TDF after RDT may be a more feasible strategy to implement in RLS, TDF after HBeAg test is a less costly option.
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Affiliation(s)
- Marieke Bierhoff
- grid.10223.320000 0004 1937 0490Shoklo Malaria Research Unit, Mahidol-Oxford Tropical Medicine Research Unit, Mahidol University, Mae Sot, 63110 Thailand ,grid.7177.60000000084992262Division of Infectious Diseases, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
| | - Chaisiri Angkurawaranon
- grid.7132.70000 0000 9039 7662Department of Family Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200 Thailand
| | - Marcus J. Rijken
- grid.7177.60000000084992262Department of Obstetrics and Gynaecology, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands
| | - Kanlaya Sriprawa
- grid.10223.320000 0004 1937 0490Shoklo Malaria Research Unit, Mahidol-Oxford Tropical Medicine Research Unit, Mahidol University, Mae Sot, 63110 Thailand
| | - Pachinee Kobphan
- grid.10223.320000 0004 1937 0490Shoklo Malaria Research Unit, Mahidol-Oxford Tropical Medicine Research Unit, Mahidol University, Mae Sot, 63110 Thailand
| | - Francois N. Nosten
- grid.10223.320000 0004 1937 0490Shoklo Malaria Research Unit, Mahidol-Oxford Tropical Medicine Research Unit, Mahidol University, Mae Sot, 63110 Thailand ,grid.4991.50000 0004 1936 8948Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine Research Building, University of Oxford, Oxford, OX3 7FZ UK
| | - Michèle van Vugt
- grid.7177.60000000084992262Division of Infectious Diseases, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
| | - Rose McGready
- grid.10223.320000 0004 1937 0490Shoklo Malaria Research Unit, Mahidol-Oxford Tropical Medicine Research Unit, Mahidol University, Mae Sot, 63110 Thailand ,grid.4991.50000 0004 1936 8948Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine Research Building, University of Oxford, Oxford, OX3 7FZ UK
| | - Angela Devine
- grid.1043.60000 0001 2157 559XDivision of Global and Tropical Health, Menzies School of Health Research, Charles Darwin University, Casuarina, Australia ,grid.1008.90000 0001 2179 088XCentre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Parkvilles, Australia
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11
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Chilaka VN, Konje JC. Viral Hepatitis in pregnancy. Eur J Obstet Gynecol Reprod Biol 2020; 256:287-296. [PMID: 33259998 DOI: 10.1016/j.ejogrb.2020.11.052] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2020] [Revised: 11/13/2020] [Accepted: 11/18/2020] [Indexed: 12/20/2022]
Abstract
The global prevalence of viral hepatitis is very high and seems to be rising over the years. The infection can profoundly affect pregnant women causing significant maternal and perinatal morbidity and mortality with some strains much worse than others. Hepatitis A (HAV) and E (HEV) which are transmitted mainly through the faecal-oral route present as acute hepatitis during pregnancy and are responsible for most local epidemic outbreaks. HAV infection remains self-limiting during pregnancy, while HEV has a higher prevalence and causes significant morbidity. It is also associated with a very high maternal mortality rate (20 %) and requires special attention in endemic areas. HEV vaccines do exist, but the WHO has yet to approve them for general use. Hepatitis B is the most prevalent form and is part of the ante-natal screening program. The presence of HBeAg is associated with high viral loads and infectivity. Antiviral therapy, preferably tenofovir (TDF), is recommended for mothers with viral load ≥ 200,000 IU/mL2), with the neonates receiving both active and passive immunisations. Hepatitis C and D are usually found as chronic infections in the pregnant and non-pregnant populations. Screening for hepatitis C during pregnancy and its subsequent management is still unsettled, but the introduction of direct-acting antiviral (DAA) drugs will change the picture if their safety is established in pregnancy. HDV is an incomplete virus linked to HBV and cannot establish an infection on its own. Controlling HBV is paramount to controlling HDV. HEV is quite prevalent and looked upon as hepatotropic. It seems to be quite prevalent in some blood donor populations and has a high co-infection rate with HCV. It has a high Mother-to-Child-Transmission (MTCT) but causes little or no illness in infected infants, and antenatal screening is not justified. This review summarises the prevalence, clinical picture, maternal, perinatal effects, and the management and prevention of hepatitis A, B, C, D, E and G viral infections during pregnancy.
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Affiliation(s)
- Victor N Chilaka
- Women's Wellness Research Center, Hamad Medical Corporation, Doha, Qatar; Weill Cornell Medicine, Doha, Qatar.
| | - Justin C Konje
- Weill Cornell Medicine, Doha, Qatar; Sidra Medicine, Doha, Qatar; University of Leicester, UK
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12
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Efficacy and Safety of Tenofovir in the Prevention of Perinatal Transmission of Hepatitis B, a Meta-Analysis. GASTROENTEROLOGIA Y HEPATOLOGIA 2020; 43:640-648. [PMID: 32948358 DOI: 10.1016/j.gastrohep.2020.03.015] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/20/2019] [Revised: 02/23/2020] [Accepted: 03/31/2020] [Indexed: 01/02/2023]
Abstract
BACKGROUND Tenofovir disoproxil fumarate (TDF) is recommended for the prevention of perinatal transmission of the hepatitis B virus (HBV). This study aimed to systematically assess the efficacy and safety of TDF in pregnant women with chronic HBV and their infants. MATERIAL AND METHODS Database searches were performed to identify studies blocking the mother-to-child transmission of the hepatitis B virus with tenofovir. The search included pregnant women with chronic HBV infection administered with TDF compared to the no treatment controls, and data from individual studies were pooled using RevMan v5.3 for meta-analysis. RESULTS Seven studies with a total of 911 patients met the inclusion criteria: 433 patients in the TDF group and 478 patients in the non-TDF group. The HBV mother-to-child transmission rate in the tenofovir group was effectively reduced compared to the control group (RR: 0.18, 95% CI: 0.08-0.40). HBV-DNA positivity was also significantly low in infants from TDF group (RR: 0.17, 95% CI: 0.10-0.30) and the TDF treatment resulted in significantly higher anti-HBs production (RR: 1.11, 95% CI: 1.04-1.18). Similarly, maternal HBV-DNA was suppression was significantly high in the TDF group (RR: 34.16, 95% CI: 16.40-71.13). Women treated with TDF and their infants did not result in serious adverse events that are statistically different as compared to the women who did not receive any treatment. CONCLUSION Treatment of HBV infected pregnant women with TDF can effectively and safely prevent the perinatal transmission of chronic hepatitis B.
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13
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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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14
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Liu J, Wang J, Yan T, Du D, Qi C, Cao F, Yao N, Yang Y, He Y, Tian Z, Ren D, Zhu L, Chen T, Zhao Y. Efficacy and safety of telbivudine and tenofovir disoproxil fumarate in preventing hepatitis B vertical transmission: A real-life practice. J Viral Hepat 2019; 26:1170-1177. [PMID: 31177596 DOI: 10.1111/jvh.13156] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/11/2019] [Revised: 04/17/2019] [Accepted: 05/08/2019] [Indexed: 12/12/2022]
Abstract
Mother-to-child transmission (MTCT) is a major obstacle in the elimination of hepatitis B virus (HBV) infection. Telbivudine (LdT) and tenofovir disoproxil fumarate (TDF) are the two most common antiviral medicines for preventing MTCT. However, the efficacy and safety of LdT and TDF in preventing HBV vertical transmission during the second to third trimester have not been compared rigorously. Therefore, we carried out a prospective multicentre cohort study of chronic hepatitis B in mothers with HBV DNA > 106 IU/mL, receiving LdT or TDF during the second to third trimester. Among the 893 mothers enrolled, 857 (LdT/TDF/untreated group (NTx) = 396/325/136) completed consecutive follow-up with 854 infants (LdT/TDF/NTx = 395/323/136). LdT and TDF treatment resulted in a similar decrease of HBV DNA in mothers at delivery. Multivariate analysis indicated that only HBsAg titre at the baseline correlated with viral DNA decrease (P = 0.015). With intention-to-treat analysis, MTCT rates in the LdT, TDF and NTx group were 4.41%, 2.42% and 22.08%, respectively. An increasing vertical transmission rate was found to be closely associated with higher HBsAg titre, 5.32% and 17.65% infection rate was estimated in infants born to mothers with HBsAg > 4 and >5 log10 IU/mL, respectively. No serious side effects were reported in either mothers or infants. LdT and TDF treatments were well tolerated and showed comparable efficacy in reducing MTCT. Higher risk of MTCT was shown in pregnant women with HBsAg > 4 log10 IU/mL.
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Affiliation(s)
- Jinfeng Liu
- Department of Infectious Diseases, The First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, China
| | - Jing Wang
- Department of Rheumatology and Immunology, The First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, China
| | - Taotao Yan
- Department of Infectious Diseases, The First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, China
| | - Dan Du
- Department of Infectious Diseases, The First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, China
| | - Caijing Qi
- Department of Gynecology and Obstetrics, The First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, China
| | - Furong Cao
- Department of Neonatology, The First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, China
| | - Naijuan Yao
- Department of Infectious Diseases, The First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, China
| | - Yuan Yang
- Department of Infectious Diseases, The First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, China
| | - Yingli He
- Department of Infectious Diseases, The First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, China
| | - Zhen Tian
- Department of Infectious Diseases, The First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, China
| | - Danfeng Ren
- Department of Infectious Diseases, The First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, China
| | - Li Zhu
- Department of Infectious Diseases, The First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, China
| | - Tianyan Chen
- Department of Infectious Diseases, The First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, China
| | - Yingren Zhao
- Department of Infectious Diseases, The First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, China
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15
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Wang M, Bian Q, Zhu Y, Pang Q, Chang L, Li R, Tiongson BC, Zhang H, Pan CQ. Real-world study of tenofovir disoproxil fumarate to prevent hepatitis B transmission in mothers with high viral load. Aliment Pharmacol Ther 2019; 49:211-217. [PMID: 30506691 DOI: 10.1111/apt.15064] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/16/2018] [Revised: 08/05/2018] [Accepted: 10/27/2018] [Indexed: 12/13/2022]
Abstract
BACKGROUND Data on tenofovir disoproxil fumarate (TDF) therapy for preventing vertical transmission of hepatitis B virus (HBV) in the real-world setting are limited. AIM To investigate TDF for preventing vertical transmission of HBV in real-world practice. METHODS Hepatitis B e-antigen (HBeAg)-positive mothers with HBV-DNA >6 log10 IU/mL to receive TDF between gestational weeks 24-33 and delivery were prospectively enrolled and followed until post-partum week 28. All infants received immunoprophylaxis. Primary endpoints were safety of TDF use and mother-to-child transmission rates. Secondary outcomes were maternal HBV-DNA level suppression (<200 000 IU/mL) at delivery and HBeAg and hepatitis B surface antigen (HBsAg) serologic changes during the study. RESULTS Among 147 mothers enrolled, 143 started TDF and 143/144 infants completed the study. At delivery, 93.7% (134/143) of the mothers achieved HBV-DNA<200 000 IU/L. On-treatment, alanine aminotransferase (ALT) flares were observed in 8.4% (12/143) of mothers. After TDF cessation, ALT increased in 7.7% (11/143) of the mothers and 2.8% (4/143) achieved HBeAg negativity, but none had HBsAg loss. At birth, HBsAg was detected in 13.9% (20/144) of newborns and none at post-partum week 28. Vertical transmission rates among infants were 0.7% (1/144, intention-to-treat) and 0% (per-protocol). No infants had birth defects. No serious adverse effects were reported in either mothers or infants. Breastfeeding did not increase the HBV infection rate among infants although mothers had viral rebound after TDF cessation. CONCLUSIONS TDF for highly viraemic mothers was well tolerated and reduced vertical transmission of HBV in a real-world setting. There were no safety concerns during the postpartum 28-week follow-up. Registry number: Chinese Clinical Trial Registration No. ChiCTR-OIC-17010869.
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Affiliation(s)
- Ming Wang
- Department of Obstetrics and Gynecology, Beijing Youan Hospital, Capital Medical University, Beijing, China
| | - Qian Bian
- Department of Obstetrics and Gynecology, Beijing Youan Hospital, Capital Medical University, Beijing, China
| | - Yunxia Zhu
- Department of Obstetrics and Gynecology, Beijing Youan Hospital, Capital Medical University, Beijing, China
| | - Qiumei Pang
- Department of Obstetrics and Gynecology, Beijing Youan Hospital, Capital Medical University, Beijing, China
| | - Lingzhi Chang
- Department of Obstetrics and Gynecology, Beijing Youan Hospital, Capital Medical University, Beijing, China
| | - Ran Li
- Department of Obstetrics and Gynecology, Beijing Youan Hospital, Capital Medical University, Beijing, China
| | | | - Hua Zhang
- Department of Obstetrics and Gynecology, Beijing Youan Hospital, Capital Medical University, Beijing, China
| | - Calvin Q Pan
- Division of Gastroenterology, Department of Medicine, NYU Langone Health, NYU School of Medicine, New York City, NY
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16
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Lin Y, Liu Y, Ding G, Touqui L, Wang W, Xu N, Liu K, Zhang L, Chen D, Wu Y, Bai G. Efficacy of tenofovir in preventing perinatal transmission of HBV infection in pregnant women with high viral loads. Sci Rep 2018; 8:15514. [PMID: 30341345 PMCID: PMC6195597 DOI: 10.1038/s41598-018-33833-w] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2018] [Accepted: 10/03/2018] [Indexed: 12/12/2022] Open
Abstract
Mother-to-child transmission is the major cause of chronic hepatitis B virus (HBV) infection. This double-blind trial tested the effect of tenofovir disoproxil fumarate (TDF) in preventing vertical transmission. Pregnant women who were HBsAg/HBeAg-positive with a HBV DNA titer ≥ 2×106 IU/mL were randomly assigned to the control (n = 60) and TDF-treated (n = 60) groups. TDF treatment (oral dose 300 mg/day) was initiated at 24 weeks of gestation and continued to 4 weeks after delivery. The subjects were followed up to 28 weeks postpartum. The effects of TDF on vertical transmission, outcomes of the mothers and infants and virological changes were monitored. TDF dynamically reduced the serum HBV DNA level of the mothers, particularly during the first 4 weeks of treatment. The lower viral loads were maintained in the pregnancies until delivery. Approximately 90% and 33.9% of the TDF-treated mothers had viral loads ≤2000 IU/mL after delivery and at 28 weeks postpartum, respectively. No cervical transmission or adverse effects were observed in the TDF-treated individuals, whereas 13.5% of the infants were infected with HBV in the control group. We conclude that TDF treatment initiated at 24 weeks of gestation in high-viremia, HBsAg/HBeAg-positive mothers efficiently prevents mother-to-child HBV transmission without adverse events in mothers and infants.
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Affiliation(s)
- Yayun Lin
- Department of Gynecology and Obstetrics, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Yan Liu
- Research Center for Clinical and Translational Medicine/Institute of Infectious Diseases, Beijing 302 Hospital, Beijing, China
| | - Guifeng Ding
- Department of Obstetrics, Maternal and Child Health Care Hospital of Xinjiang Uygur Autonomous Region, Urumqi, China
| | - Lhousseine Touqui
- Equipe Mixte Institut Pasteur/Paris V, Department of Infection & Epidemiology, Institut Pasteur, Paris, France
| | - Weimin Wang
- Department of Gynecology and Obstetrics, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Na Xu
- Department of Gynecology and Obstetrics, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Keying Liu
- Department of Gynecology and Obstetrics, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Lingyan Zhang
- Department of Gynecology and Obstetrics, ShaanXi Provincial People Hospital, Xi'an, China
| | - Dunjin Chen
- Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
| | - Yongzheng Wu
- Unit of Cellular Biology of Microbial Infection/CNRS UMR3691, Institut Pasteur, Paris, France.
| | - Guiqin Bai
- Department of Gynecology and Obstetrics, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
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Kar P, Sengupta A. Synthetic therapeutics for the treatment of hepatitis B during pregnancy. Expert Opin Pharmacother 2018; 19:1771-1778. [PMID: 30273073 DOI: 10.1080/14656566.2018.1527313] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/28/2022]
Abstract
INTRODUCTION Hepatitis B infection in pregnancy mandates careful monitoring and specialized management according to the phase of hepatitis B infection. Perinatal transmission may be prevented by antiviral therapy in mothers with high viral load and timely immunoprophylaxis of the infant. AREAS COVERED This review focuses on the current first-line therapies for treating hepatitis B in pregnancy, timing of therapy, and prevention of perinatal transmission. Strategies to manage disease at the various phases and potential emerging therapies in phase III of development are also covered. Medline/PubMed and Cochrane databases were searched systematically from 1990 to April 2018 with the relevant articles selected for the review. EXPERT OPINION Universal antenatal screening for hepatitis B and strict immunoprophylaxis for infants form the cornerstones to prevent hepatitis B virus (HBV) perinatal transmission. Tenofovir is the preferred drug for treatment in pregnancy in view of its good efficacy and high barrier to resistance. Most of the data on antivirals are from cohort studies which are prone to bias and more randomized controlled trials (RCTs) are needed to establish the benefits and safety of these drugs in pregnancy. Various novel drugs are in the pipeline which may pave the way for a cure in the near future.
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Affiliation(s)
- Premashis Kar
- a Department of Gastroenterology and Hepatology , Max Super Speciality Hospital, Vaishali , Ghaziabad , India
| | - Anando Sengupta
- a Department of Gastroenterology and Hepatology , Max Super Speciality Hospital, Vaishali , Ghaziabad , India
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18
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Kushner T, Sarkar M. Chronic Hepatitis B in Pregnancy. Clin Liver Dis (Hoboken) 2018; 12:24-28. [PMID: 30988905 PMCID: PMC6385901 DOI: 10.1002/cld.727] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/03/2018] [Accepted: 05/05/2018] [Indexed: 02/06/2023] Open
Affiliation(s)
- Tatyana Kushner
- Icahn School of Medicine at Mount SinaiDepartment of Medicine, Division of Liver DiseasesNew YorkNY
| | - Monika Sarkar
- Division of Gastroenterology and Hepatology, Department of MedicineUniversity of California, San FranciscoSan FranciscoCA
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19
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Li W, Jia L, Zhao X, Wu X, Tang H. Efficacy and safety of tenofovir in preventing mother-to-infant transmission of hepatitis B virus: a meta-analysis based on 6 studies from China and 3 studies from other countries. BMC Gastroenterol 2018; 18:121. [PMID: 30071845 PMCID: PMC6090972 DOI: 10.1186/s12876-018-0847-2] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/05/2018] [Accepted: 07/16/2018] [Indexed: 12/26/2022] Open
Abstract
BACKGROUND The vertical transmission of HBV from mothers to their infants at birth or in early infancy has a significant role in the endemicity of HBV infection. Tenofovir is one of the most potent anti-HBV agents with a high genetic barrier to resistance. The study is to evaluate the efficacy of tenofovir in preventing perinatal HBV transmission, as well as monitoring safety for mothers and infants. METHODS PubMed, Embase, Web of Science, and CNKI (National Knowledge Infrastructure, China) database were systematically reviewed for studies that compared the efficacy and safety of tenofovir with other treatments. Pooled estimates were expressed with weight mean difference (WMD) with 95% confidence intervals (95% CIs) and risk ratio (RR) with 95% CIs. RESULTS Nine studies involving 1046 pregnant patients met the inclusion criteria and were included in this meta-analysis. Compared with other treatments, tenofovir significantly reduced maternal HBV DNA levels (WMD = 2.33 log10 IU/mL, 95% CI: 1.01, 3.64; P < 0.001), infant HBsAg positivity rate (RR = 0.25, 95% CI: 0.16, 0.38; P < 0.001), infant HBeAg positivity rate (RR = 0.26, 95% CI: 0.14, 0.48; P < 0.001), infant HBV DNA positivity rate (RR = 0.15, 95% CI: 0.07, 0.31; P < 0.001), and immunoprophylaxis failure rate (RR = 0.31, 95% CI: 0.13, 0.73; P = 0.008). Moreover, maternal and infant safety profiles, including ALT, CK, and Cr were comparable between tenofovir and other treatment groups. CONCLUSION Based on the current evidence, our study suggested that tenofovir significantly reduced the rate of vertical transmission of HBV, as well as the HBV DNA levels in HBV-infected mothers. Moreover, tenofovir was safe and tolerable for both mothers and their infants.
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Affiliation(s)
- Wenhui Li
- Department of Infectious Disease, Children’s Hospital of Hebei Province, 133 South Jianhua Street, Shijiazhuang, 050031 Hebei China
| | - Li Jia
- Department of Infectious Disease, Children’s Hospital of Hebei Province, 133 South Jianhua Street, Shijiazhuang, 050031 Hebei China
| | - Xin Zhao
- Department of Infectious Disease, Children’s Hospital of Hebei Province, 133 South Jianhua Street, Shijiazhuang, 050031 Hebei China
| | - Xiaoyuan Wu
- Department of Infectious Disease, Children’s Hospital of Hebei Province, 133 South Jianhua Street, Shijiazhuang, 050031 Hebei China
| | - Hongxia Tang
- Department of Neurology, Children’s Hospital of Hebei Province, 133 South Jianhua Street, Shijiazhuang, 050031 Hebei China
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Dionne-Odom J, Njei B, Tita ATN. Elimination of Vertical Transmission of Hepatitis B in Africa: A Review of Available Tools and New Opportunities. Clin Ther 2018; 40:1255-1267. [PMID: 29983265 PMCID: PMC6123260 DOI: 10.1016/j.clinthera.2018.05.016] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2018] [Revised: 05/21/2018] [Accepted: 05/21/2018] [Indexed: 02/06/2023]
Abstract
PURPOSE This review article focuses on preventing vertical transmission of hepatitis B virus (HBV) among pregnant women living in sub-Saharan Africa (SSA), where disease is endemic and the estimated maternal HBV seroprevalence is >8%. Available interventions that have been studied in low- and middle-income countries are compared in terms of efficacy and effectiveness in clinical practice. Global disease-elimination targets, barriers to HBV-prevention efforts, and critical research gaps are discussed. METHODS A PubMed literature search in February 2018 identified relevant studies of interventions to reduce or prevent the transmission of HBV during pregnancy or in the peripartum period. Studies that focused on interventions that are currently available or could be made available in SSA were included. Trials conducted in SSA and other low-income countries were prioritized, although studies of interventions in middle- and high-income countries were included. FINDINGS Among 127 studies and reports included in the review, 60 included data from SSA. The most cost-effective intervention to reduce HBV infection rates in SSA is timely birth-dose vaccination followed by completion of the 3-dose infant-vaccination series. The identification and treatment of pregnant women with elevated HBV viral load to further reduce the risk for vertical transmission in SSA show promise, but efficacy and tolerability trials in Africa are lacking. IMPLICATIONS Scale-up of currently available tools is required to reach HBV disease-elimination goals in SSA. Many countries in SSA are in the process of rolling out national birth-dose vaccination campaigns; this roll out provides an opportunity to evaluate and improve processes in order to expand coverage. Early antenatal care, promotion of facility deliveries, and increased awareness of HBV prevention are also key components of prevention success. Future studies in SSA should identity an HBV-prevention package that is effective, well tolerated, and feasible and can be administered in the antenatal clinic and tailored to vertical-transmission risk.
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Affiliation(s)
- Jodie Dionne-Odom
- Department of Medicine, Division of Infectious Diseases, University of Alabama, Birmingham, Alabama.
| | - Basile Njei
- Department of Medicine, Section of Digestive Disease, Yale University, New Haven, Connecticut
| | - Alan T N Tita
- Department of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, Center for Women's Reproductive Health, University of Alabama, Birmingham, Alabama
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21
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Abstract
Hepatitis B virus and hepatitis C virus have received a significant amount of attention in recent years, and both viruses share a significant amount of similarities with one another beyond just that they both primarily target the liver. In recent years, cases of both infections have been fueled by a nationwide epidemic of injection drug use. Most relevant to this audience, they are both transmitted from mother to child. The increased cases in young adults combined with mother to child transmission translate into more exposed infants that will need to be managed and followed. Screening of pregnant women for hepatitis B infection coupled with appropriate treatment and prophylaxis measures are incredibly effective to preventing transmission. Prevention of hepatitis C infection is not yet possible, but advances in antiviral therapy make interruption of transmission a future possibility.
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Affiliation(s)
- Claudia M Espinosa
- Division of Pediatric Infectious Diseases, University of Louisville School of Medicine, Louisville, KY
| | - Ravi Jhaveri
- Division of Infectious Diseases, Department of Pediatrics, UNC School of Medicine, Campus Box 7231, Chapel Hill, NC 27599-7231.
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22
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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] [MESH Headings] [Grants] [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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Tavakolpour S, Darvishi M, Mirsafaei HS, Ghasemiadl M. Nucleoside/nucleotide analogues in the treatment of chronic hepatitis B infection during pregnancy: a systematic review. Infect Dis (Lond) 2018; 50:95-106. [PMID: 29020844 DOI: 10.1080/23744235.2017.1384957] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/31/2017] [Revised: 09/15/2017] [Accepted: 09/18/2017] [Indexed: 12/18/2022] Open
Abstract
BACKGROUND Women of childbearing age who have developed chronic hepatitis B (CHB) infection, especially HBeAg-positive highly viraemic pregnant women, are largely responsible for the familial transmission of the infection. Therefore, choosing the most effective and safest antiviral medications to manage pregnant CHB patients is of crucial importance. MATERIALS AND METHODS The PubMed and Scopus databases were searched through September 2017, for all the journal articles possessing original results regarding treatment of CHB pregnant women with any nucleos(t)ide analogue (NA) therapies, including lamivudine (LAM), adefovir (ADV), entecavir (ETV), telbivudine (LdT), and tenofovir (TDF). RESULTS After the primary search, 882 studies were recognized, and updating the searching results, 41 journal articles with original data were investigated, involving 3874 newborn infants from mothers with CHB, and their mothers completed follow-up until the delivery. The most important basic data and results regarding the efficacy of drugs, the rate of vertical transmission, safety issues associated with pairs of mothers and infants, median levels of HBV DNA, breastfeeding data, and rate of rate of vaccination success were collected. Moreover, possible key conclusion, recommendations, and learned lessons were discussed. Among the evaluated NAs, all LAM was efficient and safe. LdT was found to be very effective but had some safety concerns. In contrast, TDF had the advantages of both effectiveness and safety. CONCLUSION According to data in the literature, initiation of TDF at the trimester of pregnancy in combination with immunoprophylaxis to prevent mother-to-child transmission (MTCT) of CHB infection is strongly recommended as well as successful immunization of CHB pregnant women by anti-HBV vaccines.
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Affiliation(s)
- Soheil Tavakolpour
- a Infectious Diseases and Tropical Medicine Research Center , Shahid Beheshti University of Medical Sciences , Tehran , Iran
| | - Mohammad Darvishi
- b Department of Aerospace and Subaquatic Medicine, Infectious Diseases and Tropical Medicine Research Center (IDTMRC) , AJA University of Medical Sciences , Tehran , Iran
| | - Hajar Sadat Mirsafaei
- a Infectious Diseases and Tropical Medicine Research Center , Shahid Beheshti University of Medical Sciences , Tehran , Iran
| | - Mojtaba Ghasemiadl
- a Infectious Diseases and Tropical Medicine Research Center , Shahid Beheshti University of Medical Sciences , Tehran , Iran
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Hou J, Wang G, Wang F, Cheng J, Ren H, Zhuang H, Sun J, Li L, Li J, Meng Q, Zhao J, Duan Z, Jia J, Tang H, Sheng J, Peng J, Lu F, Xie Q, Wei L, Chinese Society of Hepatology, Chinese Medical Association, Chinese Society of Infectious Diseases, Chinese Medical Association. Guideline of Prevention and Treatment for Chronic Hepatitis B (2015 Update). J Clin Transl Hepatol 2017; 5:297-318. [PMID: 29226097 PMCID: PMC5719188 DOI: 10.14218/jcth.2016.00019] [Citation(s) in RCA: 165] [Impact Index Per Article: 20.6] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/03/2016] [Revised: 01/14/2017] [Accepted: 01/16/2017] [Indexed: 02/05/2023] Open
Affiliation(s)
- Jinlin Hou
- Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China
- *Correspondence to: Jinlin Hou, Department of Infectious Diseases and Hepatology Unit, Nanfang Hospital, Southern Medical University, No. 1838 North Guangzhou avenue, Guangzhou 510515, China. E-mail: ; Lai Wei, Peking University People’s Hospital, Peking University Hepatology Institute, No. 11 Xizhimen South Street, Beijing 100044, China. E-mail:
| | - Guiqiang Wang
- Department of Infectious Diseases, Center for Liver Diseases, Peking University First Hospital, Beijing, China
| | - Fusheng Wang
- The Institute of Translational Hepatology, 302 Hospital of PLA, Peking University, Beijing, China
| | - Jun Cheng
- Center of Liver Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Hong Ren
- Institute for Viral Hepatitis, the Key Laboratory of Molecular Biology for Infectious Diseases, the second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Hui Zhuang
- Department of Microbiology of Peking University Health Science Center, Beijing, China
| | - Jian Sun
- Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Lanjuan Li
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Jie Li
- Department of Microbiology of Peking University Health Science Center, Beijing, China
| | - Qinghua Meng
- Serious Illness Medicine Inpatient Area, Beijing Youan Hospital, Capital Medical University, Beijing, China
| | - Jingmin Zhao
- Department of Pathology, 302 Hospital of PLA, Peking University, Beijing, China
| | - Zhongping Duan
- Artificial Liver Center, Beijing Youan Hospital, Capital Medical University, Beijing, China
| | - Jidong Jia
- Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Hong Tang
- Center of Infectious Diseases, West China Hospital of Sichuan University, Division of Infectious Diseases, State Key Laboratory of Biotherapy, Sichuan University, Chengdu, China
| | - Jifang Sheng
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Jie Peng
- Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Fengmin Lu
- Department of Microbiology of Peking University Health Science Center, Beijing, China
| | - Qing Xie
- Department of Infectious Diseases, Shanghai Jiao Tong University School of Medicine Affiliated Ruijin Hospital, Shanghai, China
| | - Lai Wei
- Hepatology Institute, Peking University People’s Hospital, Beijing, China
- *Correspondence to: Jinlin Hou, Department of Infectious Diseases and Hepatology Unit, Nanfang Hospital, Southern Medical University, No. 1838 North Guangzhou avenue, Guangzhou 510515, China. E-mail: ; Lai Wei, Peking University People’s Hospital, Peking University Hepatology Institute, No. 11 Xizhimen South Street, Beijing 100044, China. E-mail:
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Epidemiology of chronic hepatitis B virus in Ireland using routinely collected surveillance and administrative data, 2004-2014. Ir J Med Sci 2017; 187:803-811. [PMID: 29224133 DOI: 10.1007/s11845-017-1720-y] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2017] [Accepted: 11/16/2017] [Indexed: 12/15/2022]
Abstract
BACKGROUND Ireland has a low prevalence of chronic hepatitis B virus (HBV) infection; however, there are limited recently published epidemiological data. This study aimed to describe the epidemiology of chronic HBV in Ireland between 2004 and 2014 using routine surveillance data and identify and interrogate additional data sources in Ireland to complement the interpretation of HBV surveillance data. METHODS Routinely collected passive surveillance data of notified cases of HBV infection were collated for 2004-2014. Additional data sources relating to primary liver cancer and cirrhosis were collated, including hospital discharge data (2005-2013), diagnoses of primary liver cancer (2004-2013), and deaths (2007-2014). Publicly available immigration (2004-2014) data were also collated. RESULTS Between 2004 and 2014, a total of 7463 notifications of HBV were made in Ireland; the majority (91%) were classified as chronic cases. Notifications peaked in 2008 and decreased until 2013. Hospital discharges, new cancer registrations, and deaths from primary liver cancer and hospital discharges from cirrhosis have increased each year. DISCUSSION The epidemiology of HBV in Ireland mirrors immigration patterns. Without a coordinated screening and care programme for priority populations, particularly for immigrants from high prevalence countries, it is likely that hospitalisations and deaths from HBV-attributable cirrhosis and primary liver cancer will continue to rise, with considerable associated public health expense.
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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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Abstract
Chronic hepatitis B virus (HBV) infection due to mother-to-child transmission during the perinatal period remains an important global health problem. Despite standard passive-active immunoprophylaxis with hepatitis B immunoglobulin and hepatitis B vaccine in neonates, up to 8.5% of newborns still acquire HBV infection. Thus, management of chronic HBV during pregnancy and strategies to prevent mother-to-child transmission are important steps in eradicating or reducing the global burden of chronic HBV infection. To date, the management of HBV infection in pregnancy still needs careful attention because of some controversial aspects, including the influence of pregnancy on the course of HBV replication, safety of antiviral prophylaxis with nucleus(t)ide analogs, postpartum flares of hepatitis after delivery, and the safety of breastfeeding. In this review, we highlight these important issues of preventive strategies in the perinatal period.
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Quantifying perinatal transmission of Hepatitis B viral quasispecies by tag linkage deep sequencing. Sci Rep 2017; 7:10168. [PMID: 28860476 PMCID: PMC5578979 DOI: 10.1038/s41598-017-10591-9] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2017] [Accepted: 08/11/2017] [Indexed: 02/07/2023] Open
Abstract
Despite full immunoprophylaxis, mother-to-child transmission (MTCT) of Hepatitis B Virus still occurs in approximately 2–5% of HBsAg positive mothers. Little is known about the bottleneck of HBV transmission and the evolution of viral quasispecies in the context of MTCT. Here we adopted a newly developed tag linkage deep sequencing method and analyzed the quasispecies of four MTCT pairs that broke through immunoprophylaxis. By assigning unique tags to individual viral sequences, we accurately reconstructed HBV haplotypes in a region of 836 bp, which contains the major immune epitopes and drug resistance mutations. The detection limit of minor viral haplotypes reached 0.1% for individual patient sample. Dominance of “a determinant” polymorphisms were observed in two children, which pre-existed as minor quasispecies in maternal samples. In all four pairs of MTCT samples, we consistently observed a significant overlap of viral haplotypes shared between mother and child. We also demonstrate that the data can be potentially useful to estimate the bottleneck effect during HBV MTCT, which provides information to optimize treatment for reducing the frequency of MTCT.
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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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Efficacy and safety of tenofovir disoproxil fumarate in preventing vertical transmission of hepatitis B in pregnancies with high viral load. Sci Rep 2017. [PMID: 28646142 PMCID: PMC5482834 DOI: 10.1038/s41598-017-04479-x] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
This study was a meta-analysis of the literature on the efficacy and safety of tenofovir disoproxil fumarate (TDF) in preventing vertical transmission of hepatitis B in pregnancies with high viral load. Four observational studies and one randomized controlled trial involving 585 pregnant women and 595 newborns were included in the meta-analysis. TDF was more effective than the placebo in reducing vertical transmission in HBeAg-positive chronic hepatitis B (CHB) pregnancies with high serum HBV-DNA levels (OR = 0.21, 95% CI = 0.07–0.61) at 4–12 months, infant HBV DNA seropositivity at delivery (OR = 0.16, 95% CI = 0.07–0.37), and a severe flair in maternal alanine aminotransferase (ALT) levels (OR = 0.43, 95% CI = 0.19–0.95) during pregnancy. In addition, TDF showed more improvement in HBV DNA suppression at delivery (OR = 254.46, 95% CI = 28.39–2280.79). No significant differences were found in HBeAg seroconversion or ALT normalization; or in rates of cesarean section, emergent cesarean section, postpartum hemorrhage, prematurity, congenital malformations, or infant death. However, TDF induced more drug-related adverse events (OR = 2.33, 95% CI = 1.39–3.89) and elevated creatine kinase (CK) (OR = 9.56, 95% CI = 1.17–78.09) than in controls. The available evidence suggests that TDF is effective and safe in preventing vertical transmission of hepatitis B in pregnancies exhibiting a high viral load.
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Hyun MH, Lee YS, Kim JH, Je JH, Yoo YJ, Yeon JE, Byun KS. Systematic review with meta-analysis: the efficacy and safety of tenofovir to prevent mother-to-child transmission of hepatitis B virus. Aliment Pharmacol Ther 2017; 45:1493-1505. [PMID: 28436552 DOI: 10.1111/apt.14068] [Citation(s) in RCA: 56] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/23/2016] [Revised: 11/27/2016] [Accepted: 03/09/2017] [Indexed: 12/12/2022]
Abstract
BACKGROUND Preventing mother to child transmission of chronic hepatitis B infection in the setting of a high maternal viral load is challenging. The idea has emerged from antepartum tenofovir treatment with combination immunoprophylaxis. AIMS To demonstrate the efficacy and safety of tenofovir to prevent mother to child transmission of hepatitis B virus. METHODS PubMed, EMBASE, and Cochrane databases were searched through August 16, 2016. Comparative trials of second or third trimester tenofovir administration vs. controls for patients with chronic hepatitis B infection and non-comparative case series assessing mother to child transmission rates and evaluating maternal and foetal safety outcomes were included. RESULTS Ten studies (one randomised controlled trial, four non-randomised controlled trials and five case series) that enrolled 733 women were included. The pooled results from comparative trials (599 pregnancies) showed that tenofovir significantly reduced the risk of infant hepatitis B surface antigen seropositivity by 77% (odds ratio=0.23, 95% confidence intervals=0.10-0.52, P=.0004) without heterogeneity (I2 =0%). In the case series analysis (134 pregnancies), only two cases (1.5%) of mother to child transmission with extremely high maternal viral load and non-compliance to treatment were identified. Maternal and foetal safety parameters including congenital malformation and foetal death were re-assuring. CONCLUSIONS For pregnant women with high hepatitis B virus DNA levels, tenofovir administration in the second or third trimester can prevent mother to child transmission when combined with hepatitis B immunoglobulin and the hepatitis B vaccine. Tenofovir is safe and tolerable for both the mother and foetus.
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Affiliation(s)
- M H Hyun
- Department of Internal Medicine, Korea University Medical Center, Seoul, Korea
| | - Y-S Lee
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Korea University Medical Center, Seoul, Korea
| | - J H Kim
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Korea University Medical Center, Seoul, Korea
| | - J H Je
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Korea University Medical Center, Seoul, Korea
| | - Y J Yoo
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Korea University Medical Center, Seoul, Korea
| | - J E Yeon
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Korea University Medical Center, Seoul, Korea
| | - K S Byun
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Korea University Medical Center, Seoul, Korea
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Prospective interventional study of tenofovir in pregnancy to prevent vertical transmission of hepatitis B in highly viremic women. Eur J Gastroenterol Hepatol 2017; 29:259-263. [PMID: 27879486 DOI: 10.1097/meg.0000000000000793] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
BACKGROUND The risk of vertical transmission of hepatitis B virus (HBV) increases as maternal HBV DNA increase, despite serovaccination to newborns. METHODS From 1 July 2012 to 1 January 2016, all pregnant women in Lariboisiere Hospital, Paris, France, with HBV DNA of 5 log10 IU/ml and above were administered tenofovir from week 28 of pregnancy until delivery. HBV DNA was measured at months 1, 2 of tenofovir and at delivery. The newborns were serovaccinated, tested for hepatitis B surface antigen, hepatitis B core antibody (HBcAb)±HBV DNA, and hepatitis B surface antibody (HBsAb) when aged 9 months, and then 24 months. This study was registered in http://www.ClinicalTrials.gov (NCT02039362). RESULTS Thirty-one women gave birth to 37 newborns. Maternal HBV DNA at baseline was 8.23 log10 IU/ml and above in 12 pregnancies. The mean (median) HBV DNA were 4.4±1.2 (4.8), 3.3±1.7 (3.8), and 2.1±1.9 (2.0) log10 IU/ml at months 1, 2 of tenofovir and at delivery, respectively. Twenty-seven newborns were followed up: none of the 19 children aged 9 months or older was positive for hepatitis B surface antigen when aged 9 months; 14 children tested positive for HBcAb (probably transferred maternal antibodies, not found when aged 24 months) and for HBsAb without HBV DNA. Four of the 19 children showed HBsAb without HBcAb, the last being doubtful for HBcAb and HBsAb without HBV DNA. Eight newborns aged less than 9 months were not tested. CONCLUSION Tenofovir from week 28 of pregnancy to highly viremic HBV women plus serovaccination to newborns could prevent chronic and past infection.
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Jaffe A, Brown RS. A Review of Antiviral Use for the Treatment of Chronic Hepatitis B Virus Infection in Pregnant Women. Gastroenterol Hepatol (N Y) 2017; 13:154-163. [PMID: 28539842 PMCID: PMC5439134] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/07/2023]
Abstract
Mother-to-child transmission (MTCT) of hepatitis B virus (HBV) remains high even with the proper use of active-passive immunoprophylaxis in newborns. Mothers with significant viremia are at a much higher risk of MTCT; therefore, treatments aimed at lowering HBV DNA levels during pregnancy may ultimately decrease global disease burden. The exact threshold for treatment remains controversial; however, most studies have accepted levels greater than 2 × 5 log10 IU/mL as significant viremia. We reviewed the most recent literature on antiviral efficacy, maternal and fetal safety, and viral resistance patterns when used for short-duration therapy in pregnancy. The literature review shows that antiviral therapy during pregnancy significantly reduces maternal HBV DNA levels with subsequent reductions in infant HBV infections. Tenofovir disoproxil fumarate (TDF) is associated with mild gastrointestinal distress and may cause decreased fetal bone growth (although long-term studies are needed to evaluate the clinical significance of this finding), and the impact of this drug is likely limited when use is restricted to the third trimester. Lamivudine and telbivudine remain inferior to TDF in regard to resistance profiles. Overall, TDF, lamivudine, and telbivudine in conjunction with standard immunoprophylaxis are recommended for use in pregnant women with significant HBV viremia (>2 × 5 log10 IU/mL) to prevent MTCT and appear reassuring in regard to their maternal and fetal safety profiles.
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Affiliation(s)
- Ariel Jaffe
- Dr Jaffe is an internal medicine resident in the Department of Medicine at Columbia University Medical Center in New York, New York. Dr Brown is the Gladys and Roland Harriman Professor of Medicine and clinical chief of the Division of Gastroenterology and Hepatology at Weill Cornell Medical College in New York, New York
| | - Robert S Brown
- Dr Jaffe is an internal medicine resident in the Department of Medicine at Columbia University Medical Center in New York, New York. Dr Brown is the Gladys and Roland Harriman Professor of Medicine and clinical chief of the Division of Gastroenterology and Hepatology at Weill Cornell Medical College in New York, New York
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Eke AC, Eleje GU, Eke UA, Xia Y, Liu J, Cochrane Hepato‐Biliary Group. Hepatitis B immunoglobulin during pregnancy for prevention of mother-to-child transmission of hepatitis B virus. Cochrane Database Syst Rev 2017; 2:CD008545. [PMID: 28188612 PMCID: PMC6464495 DOI: 10.1002/14651858.cd008545.pub2] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND Hepatitis is a viral infection of the liver. It is mainly transmitted between people through contact with infected blood, frequently from mother to baby in-utero. Hepatitis B poses significant risk to the fetus and up to 85% of infants infected by their mothers at birth develop chronic hepatitis B virus (HBV) infection. Hepatitis B immunoglobulin (HBIG) is a purified solution of human immunoglobulin that could be administered to the mother, newborn, or both. HBIG offers protection against HBV infection when administered to pregnant women who test positive for hepatitis B envelope antigen (HBeAg) or hepatitis B surface antigen (HBsAg), or both. When HBIG is administered to pregnant women, the antibodies passively diffuse across the placenta to the child. This materno-fetal diffusion is maximal during the third trimester of pregnancy. Up to 1% to 9% infants born to HBV-carrying mothers still have HBV infection despite the newborn receiving HBIG plus active HBV vaccine in the immediate neonatal period. This suggests that additional intervention such as HBIG administration to the mother during the antenatal period could be beneficial to reduce the transmission rate in utero. OBJECTIVES To determine the benefits and harms of hepatitis B immunoglobulin (HBIG) administration to pregnant women during their third trimester of pregnancy for the prevention of mother-to-child transmission of hepatitis B virus infection. SEARCH METHODS We searched the The Cochrane Hepato-Biliary Group Controlled Trials Register, CENTRAL, MEDLINE Ovid, Embase Ovid, Science Citation Index Expanded (Web of Science), SCOPUS, African Journals OnLine, and INDEX MEDICUS up to June 2016. We searched ClinicalTrials.gov and portal of the WHO International Clinical Trials Registry Platform (ICTRP) in December 2016. SELECTION CRITERIA We included randomised clinical trials comparing HBIG versus placebo or no intervention in pregnant women with HBV. DATA COLLECTION AND ANALYSIS Two authors extracted data independently. We analysed dichotomous outcome data using risk ratio (RR) and continuous outcome data using mean difference (MD) with 95% confidence intervals (CI). For meta-analyses, we used a fixed-effect model and a random-effects model, along with an assessment of heterogeneity. If there were statistically significant discrepancies in the results, we reported the more conservative point estimate. If the two estimates were equal, we used the estimate with the widest CI as our main result. We assessed bias control using the Cochrane Hepato-Biliary Group suggested bias risk domains and risk of random errors using Trial Sequential Analysis (TSA). We assessed the quality of the evidence using GRADE. MAIN RESULTS All 36 included trials originated from China and were at overall high risk of bias. The trials included 6044 pregnant women who were HBsAg, HBeAg, or hepatitis B virus DNA (HBV-DNA) positive. Only seven trials reported inclusion of HBeAg-positive mothers. All 36 trials compared HBIG versus no intervention. None of the trials used placebo.Most of the trials assessed HBIG 100 IU (two trials) and HBIG 200 IU (31 trials). The timing of administration of HBIG varied; 30 trials administered three doses of HBIG 200 IU at 28, 32, and 36 weeks of pregnancy. None of the trials reported all-cause mortality or other serious adverse events in the mothers or babies. Serological signs of hepatitis B infection of the newborns were reported as HBsAg, HBeAg, and HBV-DNA positive results at end of follow-up. Twenty-nine trials reported HBsAg status in newborns (median 1.2 months of follow-up after birth; range 0 to 12 months); seven trials reported HBeAg status (median 1.1 months of follow-up after birth; range 0 to 12 months); and 16 trials reported HBV-DNA status (median 1.2 months of follow-up; range 0 to 12 months). HBIG reduced mother-to-child transmission (MTCT) of HBsAg when compared with no intervention (179/2769 (6%) with HBIG versus 537/2541 (21%) with no intervention; RR 0.30, TSA-adjusted CI 0.20 to 0.52; I2 = 36%; 29 trials; 5310 participants; very low quality evidence). HBV-DNA reduced MTCT of HBsAg (104/1112 (9%) with HBV-DNA versus 382/1018 (38%) with no intervention; RR 0.25, TSA-adjusted CI 0.22 to 0.27; I2 = 84%; 16 trials; 2130 participants; low quality evidence). TSA supported both results. Meta-analysis showed that maternal HBIG did not decrease HBeAg in newborns compared with no intervention (184/889 (21%) with HBIG versus 232/875 (27%) with no intervention; RR 0.68, TSA-adjusted CI 0.04 to 6.37; I2 = 90%; 7 trials; 1764 participants; very low quality evidence). TSA could neither support nor refute this observation as data were too sparse. None of the trials reported adverse events of the immunoglobulins on the newborns, presence of local and systemic adverse events on the mothers, or cost-effectiveness of treatment. AUTHORS' CONCLUSIONS Due to very low to low quality evidence found in this review, we are uncertain of the effect of benefit of antenatal HBIG administration to the HBV-infected mothers on newborn outcomes, such as HBsAg, HBV-DNA, and HBeAg compared with no intervention. The results of the effects of HBIG on HBsAg and HBeAg are surrogate outcomes (raising risk of indirectness), and we need to be critical while interpreting the findings. We found no data on newborn mortality or maternal mortality or both, or other serious adverse events. Well-designed randomised clinical trials are needed to determine the benefits and harms of HBIG versus placebo in prevention of MTCT of HBV.
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Affiliation(s)
- Ahizechukwu C Eke
- Johns Hopkins University School of MedicineDivision of Maternal Fetal Medicine, Department of Gynecology and Obstetrics600 N Wolfe StreetPhipps 228BaltimoreMarylandUSA21287‐1228
| | - George U Eleje
- Faculty of Medicine, College of Health Sciences, Nnamdi Azikiwe University, Nnewi CampusEffective Care Research Unit, Department of Obstetrics and GynaecologyPMB 5001, NnewiAnambra StateNigeria
| | - Uzoamaka A Eke
- University of Connecticut Health CenterDepartment of Infectious Diseases263 Farmington AvenueFarmingtonConnecticutUSA06053
| | - Yun Xia
- Beijing University of Chinese Medicine Subsidiary Dongfang HospitalScience of EducationNo.6 District 1 Fangxingyuan, Fangzhuang, Fengtai DistrictBeijingChina100078
| | - Jiao Liu
- Beijing University of Chinese Medicine Subsidiary Dongfang HospitalNo.6 District 1 Fangxingyuan, Fangzhuang, Fengtai DistrictBeijingChina100078
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Samadi Kochaksaraei G, Congly SE, Matwiy T, Castillo E, Martin SR, Charlton CL, Coffin CS. Cost-effectiveness of quantitative hepatitis B virus surface antigen testing in pregnancy in predicting vertical transmission risk. Liver Int 2016; 36:1604-1610. [PMID: 27059287 DOI: 10.1111/liv.13139] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/13/2016] [Accepted: 03/26/2016] [Indexed: 12/13/2022]
Abstract
BACKGROUND & AIMS Vertical transmission of hepatitis B virus (HBV) can occur despite immunoprophylaxis in mothers with high HBV DNA levels (>5-7 log10 IU/ml). Quantitative hepatitis B surface antigen (qHBsAg) testing could be used as a surrogate marker to identify high viral load carriers, but there is limited data in pregnancy. We conducted a prospective observational study to determine the cost-effectiveness and utility of qHBsAg as a valid surrogate marker of HBV DNA. METHODS Pregnant patients with chronic hepatitis B were recruited from a tertiary referral centre. HBV DNA levels and qHBsAg were assessed in the second to third trimester. Statistical analysis was performed by Spearman's rank correlation and student's t-test. The cost-effectiveness of qHBsAg as compared to HBV DNA testing was calculated. RESULTS Ninety nine women with 103 pregnancies, median age 32 years, 65% Asian, 23% African and 12% other [Hispanic, Caucasian] were enrolled. Overall, 23% (23/99) were HBV e Ag (HBeAg)-positive. A significant correlation between qHBsAg and HBV DNA levels was noted in HBeAg-positive patients (r = 0.79, P < 0.05) but not in HBeAg-negative patients (r = 0.17, P = 0.06). In receiver operating characteristic analysis, the optimal qHBsAg cut-off values for predicting maternal viraemia associated with immunoprophylaxis failure (i.e., HBV DNA ≥7 log10 IU/ml) was 4.3 log10 IU/ml (accuracy 98.7%, sensitivity 94.7%, specificity 94.4%) (95% CI, 97-100%, P < 0.05). Use of HBV DNA as compared to qHBsAg costs approximately $20 000 more per infection prevented. CONCLUSION In resource poor regions, qHBsAg could be used as a more cost-effective marker for high maternal viraemia, and indicate when anti-HBV nucleos/tide analogue therapy should be used to prevent HBV immunoprophylaxis failure.
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Affiliation(s)
| | - Stephen E Congly
- Department of Medicine, University of Calgary, Calgary, AB, Canada
| | - Trudy Matwiy
- Department of Medicine, University of Calgary, Calgary, AB, Canada
| | - Eliana Castillo
- Department of Medicine, University of Calgary, Calgary, AB, Canada
| | - Steven R Martin
- Department of Pediatrics, Alberta Children's Hospital, University of Calgary, Calgary, AB, Canada
| | - Carmen L Charlton
- Provincial Laboratory for Public Health (ProvLab), University of Alberta Hospital, Edmonton, AB, Canada.,Laboratory Medicine and Pathology, University of Alberta, Edmonton, AB, Canada
| | - Carla S Coffin
- Department of Medicine, University of Calgary, Calgary, AB, Canada.
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Seroepidemiological survey of hepatitis B virus infection among 764,460 women of childbearing age in rural China: A cross-sectional study. J Clin Virol 2016; 81:47-52. [DOI: 10.1016/j.jcv.2016.05.014] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2016] [Revised: 05/21/2016] [Accepted: 05/29/2016] [Indexed: 01/12/2023]
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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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Pan CQ, Duan Z, Dai E, Zhang S, Han G, Wang Y, Zhang H, Zou H, Zhu B, Zhao W, Jiang H. Tenofovir to Prevent Hepatitis B Transmission in Mothers with High Viral Load. N Engl J Med 2016; 374:2324-2334. [PMID: 27305192 DOI: 10.1056/nejmoa1508660] [Citation(s) in RCA: 431] [Impact Index Per Article: 47.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
BACKGROUND Few data are available regarding the use of tenofovir disoproxil fumarate (TDF) during pregnancy for the prevention of mother-to-child transmission of hepatitis B virus (HBV). METHODS In this trial, we included 200 mothers who were positive for hepatitis B e antigen (HBeAg) and who had an HBV DNA level higher than 200,000 IU per milliliter. Participants were randomly assigned, in a 1:1 ratio, to receive usual care without antiviral therapy or to receive TDF (at an oral dose of 300 mg per day) from 30 to 32 weeks of gestation until postpartum week 4; the participants were followed until postpartum week 28. All the infants received immunoprophylaxis. The primary outcomes were the rates of mother-to-child transmission and birth defects. The secondary outcomes were the safety of TDF, the percentage of mothers with an HBV DNA level of less than 200,000 IU per milliliter at delivery, and loss or seroconversion of HBeAg or hepatitis B surface antigen at postpartum week 28. RESULTS At delivery, 68% of the mothers in the TDF group (66 of 97 women), as compared with 2% in the control group (2 of 100), had an HBV DNA level of less than 200,000 IU per milliliter (P<0.001). At postpartum week 28, the rate of mother-to-child transmission was significantly lower in the TDF group than in the control group, both in the intention-to-treat analysis (with transmission of virus to 5% of the infants [5 of 97] vs. 18% [18 of 100], P=0.007) and the per-protocol analysis (with transmission of virus to 0 vs. 7% [6 of 88], P=0.01). The maternal and infant safety profiles were similar in the TDF group and the control group, including birth-defect rates (2% [2 of 95 infants] and 1% [1 of 88], respectively; P=1.00), although more mothers in the TDF group had an increase in the creatine kinase level. After the discontinuation of TDF, alanine aminotransferase elevations above the normal range occurred more frequently in mothers in the TDF group than in those in the control group (45% [44 of 97 women] vs. 30% [30 of 100], P=0.03). The maternal HBV serologic outcomes did not differ significantly between the groups. CONCLUSIONS In a cohort of HBeAg-positive mothers with an HBV DNA level of more than 200,000 IU per milliliter during the third trimester, the rate of mother-to-child transmission was lower among those who received TDF therapy than among those who received usual care without antiviral therapy. (Funded by Gilead Sciences; ClinicalTrials.gov number, NCT01488526.).
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Affiliation(s)
- Calvin Q Pan
- From the Division of Gastroenterology and Hepatology, Department of Medicine, New York University (NYU) Langone Medical Center, NYU School of Medicine, New York (C.Q.P.); and the Center for Major Infectious Diseases (C.Q.P.) and Artificial Liver Center (Z.P.D., H.B.Z.), Beijing Youan Hospital, Capital Medical University, Beijing, the Division of Liver Diseases (E.H.D.) and the Department of Gynecology and Obstetrics (B.S.Z.), the Fifth Hospital of Shijiazhuang, Hebei Medical University, Shijiazhuang, the Department of Artificial Liver (S.Q.Z.) and Central Laboratory (W.J.Z.), Hepatobiliary Disease Hospital of Ji Lin Province, Changchun, the Department of Gynecology and Obstetrics, the Second Affiliated Hospital of the Southeast University, Nanjing (G.-R.H., H.-X.J.), the Institute for Infectious Diseases, Southwest Hospital, the Third Military Medical University, Chongqing (Y.W.), and the Department of Medicine, Nanyang Center Hospital, Nanyang, Henan (H.H.Z.) - all in China
| | - Zhongping Duan
- From the Division of Gastroenterology and Hepatology, Department of Medicine, New York University (NYU) Langone Medical Center, NYU School of Medicine, New York (C.Q.P.); and the Center for Major Infectious Diseases (C.Q.P.) and Artificial Liver Center (Z.P.D., H.B.Z.), Beijing Youan Hospital, Capital Medical University, Beijing, the Division of Liver Diseases (E.H.D.) and the Department of Gynecology and Obstetrics (B.S.Z.), the Fifth Hospital of Shijiazhuang, Hebei Medical University, Shijiazhuang, the Department of Artificial Liver (S.Q.Z.) and Central Laboratory (W.J.Z.), Hepatobiliary Disease Hospital of Ji Lin Province, Changchun, the Department of Gynecology and Obstetrics, the Second Affiliated Hospital of the Southeast University, Nanjing (G.-R.H., H.-X.J.), the Institute for Infectious Diseases, Southwest Hospital, the Third Military Medical University, Chongqing (Y.W.), and the Department of Medicine, Nanyang Center Hospital, Nanyang, Henan (H.H.Z.) - all in China
| | - Erhei Dai
- From the Division of Gastroenterology and Hepatology, Department of Medicine, New York University (NYU) Langone Medical Center, NYU School of Medicine, New York (C.Q.P.); and the Center for Major Infectious Diseases (C.Q.P.) and Artificial Liver Center (Z.P.D., H.B.Z.), Beijing Youan Hospital, Capital Medical University, Beijing, the Division of Liver Diseases (E.H.D.) and the Department of Gynecology and Obstetrics (B.S.Z.), the Fifth Hospital of Shijiazhuang, Hebei Medical University, Shijiazhuang, the Department of Artificial Liver (S.Q.Z.) and Central Laboratory (W.J.Z.), Hepatobiliary Disease Hospital of Ji Lin Province, Changchun, the Department of Gynecology and Obstetrics, the Second Affiliated Hospital of the Southeast University, Nanjing (G.-R.H., H.-X.J.), the Institute for Infectious Diseases, Southwest Hospital, the Third Military Medical University, Chongqing (Y.W.), and the Department of Medicine, Nanyang Center Hospital, Nanyang, Henan (H.H.Z.) - all in China
| | - Shuqin Zhang
- From the Division of Gastroenterology and Hepatology, Department of Medicine, New York University (NYU) Langone Medical Center, NYU School of Medicine, New York (C.Q.P.); and the Center for Major Infectious Diseases (C.Q.P.) and Artificial Liver Center (Z.P.D., H.B.Z.), Beijing Youan Hospital, Capital Medical University, Beijing, the Division of Liver Diseases (E.H.D.) and the Department of Gynecology and Obstetrics (B.S.Z.), the Fifth Hospital of Shijiazhuang, Hebei Medical University, Shijiazhuang, the Department of Artificial Liver (S.Q.Z.) and Central Laboratory (W.J.Z.), Hepatobiliary Disease Hospital of Ji Lin Province, Changchun, the Department of Gynecology and Obstetrics, the Second Affiliated Hospital of the Southeast University, Nanjing (G.-R.H., H.-X.J.), the Institute for Infectious Diseases, Southwest Hospital, the Third Military Medical University, Chongqing (Y.W.), and the Department of Medicine, Nanyang Center Hospital, Nanyang, Henan (H.H.Z.) - all in China
| | - Guorong Han
- From the Division of Gastroenterology and Hepatology, Department of Medicine, New York University (NYU) Langone Medical Center, NYU School of Medicine, New York (C.Q.P.); and the Center for Major Infectious Diseases (C.Q.P.) and Artificial Liver Center (Z.P.D., H.B.Z.), Beijing Youan Hospital, Capital Medical University, Beijing, the Division of Liver Diseases (E.H.D.) and the Department of Gynecology and Obstetrics (B.S.Z.), the Fifth Hospital of Shijiazhuang, Hebei Medical University, Shijiazhuang, the Department of Artificial Liver (S.Q.Z.) and Central Laboratory (W.J.Z.), Hepatobiliary Disease Hospital of Ji Lin Province, Changchun, the Department of Gynecology and Obstetrics, the Second Affiliated Hospital of the Southeast University, Nanjing (G.-R.H., H.-X.J.), the Institute for Infectious Diseases, Southwest Hospital, the Third Military Medical University, Chongqing (Y.W.), and the Department of Medicine, Nanyang Center Hospital, Nanyang, Henan (H.H.Z.) - all in China
| | - Yuming Wang
- From the Division of Gastroenterology and Hepatology, Department of Medicine, New York University (NYU) Langone Medical Center, NYU School of Medicine, New York (C.Q.P.); and the Center for Major Infectious Diseases (C.Q.P.) and Artificial Liver Center (Z.P.D., H.B.Z.), Beijing Youan Hospital, Capital Medical University, Beijing, the Division of Liver Diseases (E.H.D.) and the Department of Gynecology and Obstetrics (B.S.Z.), the Fifth Hospital of Shijiazhuang, Hebei Medical University, Shijiazhuang, the Department of Artificial Liver (S.Q.Z.) and Central Laboratory (W.J.Z.), Hepatobiliary Disease Hospital of Ji Lin Province, Changchun, the Department of Gynecology and Obstetrics, the Second Affiliated Hospital of the Southeast University, Nanjing (G.-R.H., H.-X.J.), the Institute for Infectious Diseases, Southwest Hospital, the Third Military Medical University, Chongqing (Y.W.), and the Department of Medicine, Nanyang Center Hospital, Nanyang, Henan (H.H.Z.) - all in China
| | - Huaihong Zhang
- From the Division of Gastroenterology and Hepatology, Department of Medicine, New York University (NYU) Langone Medical Center, NYU School of Medicine, New York (C.Q.P.); and the Center for Major Infectious Diseases (C.Q.P.) and Artificial Liver Center (Z.P.D., H.B.Z.), Beijing Youan Hospital, Capital Medical University, Beijing, the Division of Liver Diseases (E.H.D.) and the Department of Gynecology and Obstetrics (B.S.Z.), the Fifth Hospital of Shijiazhuang, Hebei Medical University, Shijiazhuang, the Department of Artificial Liver (S.Q.Z.) and Central Laboratory (W.J.Z.), Hepatobiliary Disease Hospital of Ji Lin Province, Changchun, the Department of Gynecology and Obstetrics, the Second Affiliated Hospital of the Southeast University, Nanjing (G.-R.H., H.-X.J.), the Institute for Infectious Diseases, Southwest Hospital, the Third Military Medical University, Chongqing (Y.W.), and the Department of Medicine, Nanyang Center Hospital, Nanyang, Henan (H.H.Z.) - all in China
| | - Huaibin Zou
- From the Division of Gastroenterology and Hepatology, Department of Medicine, New York University (NYU) Langone Medical Center, NYU School of Medicine, New York (C.Q.P.); and the Center for Major Infectious Diseases (C.Q.P.) and Artificial Liver Center (Z.P.D., H.B.Z.), Beijing Youan Hospital, Capital Medical University, Beijing, the Division of Liver Diseases (E.H.D.) and the Department of Gynecology and Obstetrics (B.S.Z.), the Fifth Hospital of Shijiazhuang, Hebei Medical University, Shijiazhuang, the Department of Artificial Liver (S.Q.Z.) and Central Laboratory (W.J.Z.), Hepatobiliary Disease Hospital of Ji Lin Province, Changchun, the Department of Gynecology and Obstetrics, the Second Affiliated Hospital of the Southeast University, Nanjing (G.-R.H., H.-X.J.), the Institute for Infectious Diseases, Southwest Hospital, the Third Military Medical University, Chongqing (Y.W.), and the Department of Medicine, Nanyang Center Hospital, Nanyang, Henan (H.H.Z.) - all in China
| | - Baoshen Zhu
- From the Division of Gastroenterology and Hepatology, Department of Medicine, New York University (NYU) Langone Medical Center, NYU School of Medicine, New York (C.Q.P.); and the Center for Major Infectious Diseases (C.Q.P.) and Artificial Liver Center (Z.P.D., H.B.Z.), Beijing Youan Hospital, Capital Medical University, Beijing, the Division of Liver Diseases (E.H.D.) and the Department of Gynecology and Obstetrics (B.S.Z.), the Fifth Hospital of Shijiazhuang, Hebei Medical University, Shijiazhuang, the Department of Artificial Liver (S.Q.Z.) and Central Laboratory (W.J.Z.), Hepatobiliary Disease Hospital of Ji Lin Province, Changchun, the Department of Gynecology and Obstetrics, the Second Affiliated Hospital of the Southeast University, Nanjing (G.-R.H., H.-X.J.), the Institute for Infectious Diseases, Southwest Hospital, the Third Military Medical University, Chongqing (Y.W.), and the Department of Medicine, Nanyang Center Hospital, Nanyang, Henan (H.H.Z.) - all in China
| | - Wenjing Zhao
- From the Division of Gastroenterology and Hepatology, Department of Medicine, New York University (NYU) Langone Medical Center, NYU School of Medicine, New York (C.Q.P.); and the Center for Major Infectious Diseases (C.Q.P.) and Artificial Liver Center (Z.P.D., H.B.Z.), Beijing Youan Hospital, Capital Medical University, Beijing, the Division of Liver Diseases (E.H.D.) and the Department of Gynecology and Obstetrics (B.S.Z.), the Fifth Hospital of Shijiazhuang, Hebei Medical University, Shijiazhuang, the Department of Artificial Liver (S.Q.Z.) and Central Laboratory (W.J.Z.), Hepatobiliary Disease Hospital of Ji Lin Province, Changchun, the Department of Gynecology and Obstetrics, the Second Affiliated Hospital of the Southeast University, Nanjing (G.-R.H., H.-X.J.), the Institute for Infectious Diseases, Southwest Hospital, the Third Military Medical University, Chongqing (Y.W.), and the Department of Medicine, Nanyang Center Hospital, Nanyang, Henan (H.H.Z.) - all in China
| | - Hongxiu Jiang
- From the Division of Gastroenterology and Hepatology, Department of Medicine, New York University (NYU) Langone Medical Center, NYU School of Medicine, New York (C.Q.P.); and the Center for Major Infectious Diseases (C.Q.P.) and Artificial Liver Center (Z.P.D., H.B.Z.), Beijing Youan Hospital, Capital Medical University, Beijing, the Division of Liver Diseases (E.H.D.) and the Department of Gynecology and Obstetrics (B.S.Z.), the Fifth Hospital of Shijiazhuang, Hebei Medical University, Shijiazhuang, the Department of Artificial Liver (S.Q.Z.) and Central Laboratory (W.J.Z.), Hepatobiliary Disease Hospital of Ji Lin Province, Changchun, the Department of Gynecology and Obstetrics, the Second Affiliated Hospital of the Southeast University, Nanjing (G.-R.H., H.-X.J.), the Institute for Infectious Diseases, Southwest Hospital, the Third Military Medical University, Chongqing (Y.W.), and the Department of Medicine, Nanyang Center Hospital, Nanyang, Henan (H.H.Z.) - all in China
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Njei B, Gupta N, Ewelukwa O, Ditah I, Foma M, Lim JK. Comparative efficacy of antiviral therapy in preventing vertical transmission of hepatitis B: a network meta-analysis. Liver Int 2016; 36:634-641. [PMID: 26352650 PMCID: PMC4824664 DOI: 10.1111/liv.12959] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/30/2015] [Accepted: 08/31/2015] [Indexed: 12/18/2022]
Abstract
BACKGROUND & AIMS Antiviral drugs are safe and effective in the third trimester to prevent intrauterine transmission of hepatitis B virus, and are recommended for hepatitis B virus (HBV) infected gravid mothers (between weeks 28 and 32) with high viral load, followed by postnatal hepatitis B immunization in the newborn. We estimated the comparative efficacy of antiviral drugs for prevention of vertical transmission of HBV, through a network meta-analysis of clinical trials. METHODS We conducted a comprehensive search of MEDLINE, EMBASE and published proceedings from major liver meetings from January 1980 to November 2014. We conducted pair-wise meta-analyses and Bayesian framework using Markov chain Monte Carlo methods, combining direct and indirect evidence for any given pair of treatments. RESULTS Seventeen clinical trials involving 2764 newborns of hepatitis B surface antigen seropositive mothers were eligible for analysis. There were no clinical trials involving tenofovir or entecavir. On pair-wise meta-analyses, telbivudine (hazard ratio, HR 0.12, 95% confidence interval (CI) 0.04-0.37; I(2) = 0%), and Lamivudine (HR 0.40, 95% CI 0.24-0.65; I(2) = 0%), were more effective than placebo in reducing vertical transmission of HBV in high viremic hepatitis B e antigen (HBeAg)-positive chronic Hepatitis B Chinese patients. Sensitivity analyses limited to studies with HBeAg seropositive mothers revealed similar results. CONCLUSIONS Based on a Bayesian network meta-analysis of clinical trials, combining direct and indirect treatment comparisons, telbivudine appears to be more effective than Lamivudine for preventing vertical transmission of HBV infection. Trials assessing the efficacy of tenofovir or entecavir compared to placebo or other antiviral drugs are lacking.
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Affiliation(s)
- Basile Njei
- Section of Digestive Diseases and Yale Liver Center, Yale University School of Medicine, New Haven, CT, USA
- Investigative Medicine Program, Yale Center of Clinical Investigation, New Haven, CT, USA
| | - Neil Gupta
- Section of Digestive Diseases and Yale Liver Center, Yale University School of Medicine, New Haven, CT, USA
| | - Oforbuike Ewelukwa
- Gastroenterology and Hepatology, University of Florida, Gainesville, FL, USA
| | - Ivo Ditah
- Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
| | - Munoh Foma
- Division of Clinical Pathology, University of Yaounde 1, Yaounde, Cameroon
| | - Joseph K. Lim
- Section of Digestive Diseases and Yale Liver Center, Yale University School of Medicine, New Haven, CT, USA
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40
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Fan L, Owusu-Edusei K, Schillie SF, Murphy TV. Cost-effectiveness of active-passive prophylaxis and antiviral prophylaxis during pregnancy to prevent perinatal hepatitis B virus infection. Hepatology 2016; 63:1471-80. [PMID: 26509655 DOI: 10.1002/hep.28310] [Citation(s) in RCA: 38] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/05/2015] [Accepted: 10/26/2015] [Indexed: 12/12/2022]
Abstract
UNLABELLED In an era of antiviral treatment, reexamination of the cost-effectiveness of strategies to prevent perinatal hepatitis B virus (HBV) transmission in the United States is needed. We used a decision tree and Markov model to estimate the cost-effectiveness of the current U.S. strategy and two alternatives: (1) Universal hepatitis B vaccination (HepB) strategy: No pregnant women are screened for hepatitis B surface antigen (HBsAg). All infants receive HepB before hospital discharge; no infants receive hepatitis B immunoglobulin (HBIG). (2) Current strategy: All pregnant women are screened for HBsAg. Infants of HBsAg-positive women receive HepB and HBIG ≤12 hours of birth. All other infants receive HepB before hospital discharge. (3) Antiviral prophylaxis strategy: All pregnant women are screened for HBsAg. HBsAg-positive women have HBV-DNA load measured. Antiviral prophylaxis is offered for 4 months starting in the third trimester to women with DNA load ≥10(6) copies/mL. HepB and HBIG are administered at birth to infants of HBsAg-positive women, and HepB is administered before hospital discharge to infants of HBsAg-negative women. Effects were measured in quality-adjusted life years (QALYs) and incremental cost-effectiveness ratios (ICER). Compared to the universal HepB strategy, the current strategy prevented 1,006 chronic HBV infections and saved 13,600 QALYs (ICER: $6,957/QALY saved). Antiviral prophylaxis dominated the current strategy, preventing an additional 489 chronic infections, and saving 800 QALYs and $2.8 million. The results remained robust over a wide range of assumptions. CONCLUSION The current U.S. strategy for preventing perinatal HBV remains cost-effective compared to the universal HepB strategy. An antiviral prophylaxis strategy was cost saving compared to the current strategy and should be considered to continue to decrease the burden of perinatal hepatitis B in the United States.
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Affiliation(s)
- Lin Fan
- National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, GA
| | - Kwame Owusu-Edusei
- National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, GA
| | - Sarah F Schillie
- National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, GA
| | - Trudy V Murphy
- National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, GA
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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] [Track Full Text] [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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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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Morisco F, Bruno R, Bugianesi E, Burra P, Calvaruso V, Cannoni A, Caporaso N, Caviglia GP, Ciancio A, Fargion S, Federico A, Floreani A, Gaeta GB, Guarino M, Invernizzi P, Licata A, Loguercio C, Mazzella G, Petraglia F, Primignani M, Rodriguez-Castro K, Smedile A, Valenti L, Vanni E, Vannuccini S, Voltolini C, Villa E. AISF position paper on liver disease and pregnancy. Dig Liver Dis 2016; 48:120-137. [PMID: 26747754 DOI: 10.1016/j.dld.2015.11.004] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/15/2015] [Revised: 10/29/2015] [Accepted: 11/06/2015] [Indexed: 12/11/2022]
Abstract
The relationship between liver disease and pregnancy is of great clinical impact. Severe liver disease in pregnancy is rare; however, pregnancy-related liver disease is the most frequent cause of liver dysfunction during pregnancy and represents a severe threat to foetal and maternal survival. A rapid differential diagnosis between liver disease related or unrelated to pregnancy is required in women who present with liver dysfunction during pregnancy. This report summarizes the recommendation of an expert panel established by the Italian Association for the Study of the Liver (AISF) on the management of liver disease during pregnancy. The article provides an overview of liver disease occurring in pregnancy, an update on the key mechanisms involved in its pathogenesis, and an assessment of the available treatment options. The report contains in three sections: (1) specific liver diseases of pregnancy; (2) liver disease occurring during pregnancy; and (3) pregnancy in patients with pre-existing chronic liver disease. Each topic is discussed considering the most relevant data available in literature; the final statements are formulated according to both scientific evidence and clinical expertise of the involved physicians, and the AISF expert panel recommendations are reported.
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Mak LY, Seto WK, Lai CL, Yuen MF. DNA polymerase inhibitors for treating hepatitis B: a safety evaluation. Expert Opin Drug Saf 2016; 15:383-92. [PMID: 26752687 DOI: 10.1517/14740338.2016.1139573] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
INTRODUCTION Oral nucleoside/ nucleotide analogues (NAs) are currently the mainstay of treatment for patients with chronic hepatitis B virus (HBV) infection. They are generally safe to use. However, since their approval in the last decade and a half, the literature has reported adverse effects associated with the use of NA in HBV patients. A comprehensive review on the drug safety is lacking. AREAS COVERED Significant adverse effects associated with NA use in HBV patients including muscle toxicity, peripheral neuropathy, nephrotoxicity and lactic acidosis are discussed. The reported prevalence of each adverse effect, as well as their predictive factors, reversibility and their use in pregnancy and lactating mothers are covered in this review. Novel data regarding reno-protective effect of telbivudine are also discussed. EXPERT OPINION Use of NA in HBV is generally safe. Uncommon adverse effects can be minimized or detected early if clinicians exercise adequate precautions when using NA for at-risk populations with regular monitoring.
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Affiliation(s)
- Lung-Yi Mak
- a Division of Gastroenterology and Hepatology, Department of Medicine , Queen Mary Hospital , Hong Kong , Hong Kong
| | - Wai-Kay Seto
- a Division of Gastroenterology and Hepatology, Department of Medicine , Queen Mary Hospital , Hong Kong , Hong Kong
| | - Ching-Lung Lai
- a Division of Gastroenterology and Hepatology, Department of Medicine , Queen Mary Hospital , Hong Kong , Hong Kong
| | - Man-Fung Yuen
- a Division of Gastroenterology and Hepatology, Department of Medicine , Queen Mary Hospital , Hong Kong , Hong Kong
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Sarin SK, Kumar M, Lau GK, Abbas Z, Chan HLY, Chen CJ, Chen DS, Chen HL, Chen PJ, Chien RN, Dokmeci AK, Gane E, Hou JL, Jafri W, Jia J, Kim JH, Lai CL, Lee HC, Lim SG, Liu CJ, Locarnini S, Al Mahtab M, Mohamed R, Omata M, Park J, Piratvisuth T, Sharma BC, Sollano J, Wang FS, Wei L, Yuen MF, Zheng SS, Kao JH. Asian-Pacific clinical practice guidelines on the management of hepatitis B: a 2015 update. Hepatol Int 2016; 10:1-98. [PMID: 26563120 PMCID: PMC4722087 DOI: 10.1007/s12072-015-9675-4] [Citation(s) in RCA: 1929] [Impact Index Per Article: 214.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/20/2015] [Accepted: 09/14/2015] [Indexed: 02/06/2023]
Abstract
Worldwide, some 240 million people have chronic hepatitis B virus (HBV), with the highest rates of infection in Africa and Asia. Our understanding of the natural history of HBV infection and the potential for therapy of the resultant disease is continuously improving. New data have become available since the previous APASL guidelines for management of HBV infection were published in 2012. The objective of this manuscript is to update the recommendations for the optimal management of chronic HBV infection. The 2015 guidelines were developed by a panel of Asian experts chosen by the APASL. The clinical practice guidelines are based on evidence from existing publications or, if evidence was unavailable, on the experts' personal experience and opinion after deliberations. Manuscripts and abstracts of important meetings published through January 2015 have been evaluated. This guideline covers the full spectrum of care of patients infected with hepatitis B, including new terminology, natural history, screening, vaccination, counseling, diagnosis, assessment of the stage of liver disease, the indications, timing, choice and duration of single or combination of antiviral drugs, screening for HCC, management in special situations like childhood, pregnancy, coinfections, renal impairment and pre- and post-liver transplant, and policy guidelines. However, areas of uncertainty still exist, and clinicians, patients, and public health authorities must therefore continue to make choices on the basis of the evolving evidence. The final clinical practice guidelines and recommendations are presented here, along with the relevant background information.
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Affiliation(s)
- S K Sarin
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India.
| | - M Kumar
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - G K Lau
- Division of Gastroenterology and Hepatology, Humanity and Health Medical Centre, Hong Kong SAR, China
- The Institute of Translational Hepatology, Beijing, China
| | - Z Abbas
- Department of Hepatogastroenterlogy, Sindh Institute of Urology and Transplantation, Karachi, Pakistan
| | - H L Y Chan
- Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, China
| | - C J Chen
- Genomics Research Center, Academia Sinica, National Taiwan University, Taipei, Taiwan
| | - D S Chen
- Department of Internal Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
| | - H L Chen
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
| | - P J Chen
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - R N Chien
- Liver Research Unit, Chang Gung Memorial Hospital and University, Chilung, Taiwan
| | - A K Dokmeci
- Department of Gastroenterology, Ankara University School of Medicine, Ankara, Turkey
| | - Ed Gane
- New Zealand Liver Transplant Unit, Auckland City Hospital, Auckland, New Zealand
| | - J L Hou
- Department of Infectious Diseases and Hepatology Unit, Nanfang Hospital, Guangzhou, China
| | - W Jafri
- Department of Medicine, Aga Khan University, Karachi, Pakistan
| | - J Jia
- Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | | | - C L Lai
- Department of Medicine, University of Hong Kong, Hong Kong, China
| | - H C Lee
- Internal Medicine Asan Medical Center, Seoul, Korea
| | - S G Lim
- Division of Gastroenterology and Hepatology, National University Health System, Singapore, Singapore
| | - C J Liu
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
| | - S Locarnini
- Research and Molecular Development, Victorian Infectious Diseases Reference Laboratory, Melbourne, Australia
| | - M Al Mahtab
- Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh
| | - R Mohamed
- Department of Medicine, Faculty of Medicine, University Malaya, Kuala Lumpur, Malaysia
| | - M Omata
- Yamanashi Hospitals (Central and Kita) Organization, 1-1-1 Fujimi, Kofu-shi, Yamanashi, 400-8506, Japan
| | - J Park
- Department of Internal Medicine, Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
| | - T Piratvisuth
- NKC Institute of Gastroenterology and Hepatology, Prince of Songkla University, Songkhla, Thailand
| | - B C Sharma
- Department of Gastroenterology, G.B. Pant Hospital, New Delhi, India
| | - J Sollano
- Department of Medicine, University of Santo Tomas, Manila, Philippines
| | - F S Wang
- Treatment and Research Center for Infectious Diseases, Beijing 302 Hospital, Beijing, China
| | - L Wei
- Peking University Hepatology Institute, Beijing, China
| | - M F Yuen
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Hong Kong, Pofulam, Hong Kong
| | - S S Zheng
- Department of Hepatobiliary and Pancreatic Surgery, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, Zhejiang Province, China
| | - J H Kao
- Graduate Institute of Clinical Medicine and Hepatitis Research Center, National Taiwan University College of Medicine, National Taiwan University Hospital, Taipei, Taiwan
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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: 48] [Impact Index Per Article: 5.3] [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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Pintye J, Langat A, Singa B, Kinuthia J, Odeny B, Katana A, Nganga L, John-Stewart G, McGrath CJ. Maternal Tenofovir Disoproxil Fumarate Use in Pregnancy and Growth Outcomes among HIV-Exposed Uninfected Infants in Kenya. Infect Dis Obstet Gynecol 2015; 2015:276851. [PMID: 26823647 PMCID: PMC4707364 DOI: 10.1155/2015/276851] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2015] [Revised: 12/02/2015] [Accepted: 12/03/2015] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Tenofovir disoproxil fumarate (TDF) is commonly used in antiretroviral treatment (ART) and preexposure prophylaxis regimens. We evaluated the relationship of prenatal TDF use and growth outcomes among Kenyan HIV-exposed uninfected (HEU) infants. MATERIALS AND METHODS We included PCR-confirmed HEU infants enrolled in a cross-sectional survey of mother-infant pairs conducted between July and December 2013 in Kenya. Maternal ART regimen during pregnancy was determined by self-report and clinic records. Six-week and 9-month z-scores for weight-for-age (WAZ), weight-for-length (WLZ), length-for-age (LAZ), and head circumference-for-age (HCAZ) were compared among HEU infants with and without TDF exposure using t-tests and multivariate linear regression models. RESULTS Among 277 mothers who received ART during pregnancy, 63% initiated ART before pregnancy, of which 89 (32%) used TDF. No differences in birth weight (3.0 kg versus 3.1 kg, p = 0.21) or gestational age (38 weeks versus 38 weeks, p = 0.16) were detected between TDF-exposed and TDF-unexposed infants. At 6 weeks, unadjusted mean WAZ was lower among TDF-exposed infants (-0.8 versus -0.4, p = 0.03), with a trend towards association in adjusted analyses (p = 0.06). There were no associations between prenatal TDF use and WLZ, LAZ, and HCAZ in 6-week or 9-month infant cohorts. CONCLUSION Maternal TDF use did not adversely affect infant growth compared to other regimens.
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Affiliation(s)
- Jillian Pintye
- Department of Global Health, University of Washington, Seattle, WA 98104, USA
- Department of Nursing, University of Washington, Seattle, WA 98195, USA
| | - Agnes Langat
- United States Centers for Disease Control and Prevention (CDC), Nairobi 00202, Kenya
| | - Benson Singa
- Center for Microbiology Research and Center for Clinical Research, Kenya Medical Research Institute, Nairobi 00202, Kenya
| | - John Kinuthia
- Department of Global Health, University of Washington, Seattle, WA 98104, USA
- Department of Obstetrics & Gynecology, Kenyatta National Hospital, Nairobi 00202, Kenya
| | - Beryne Odeny
- Department of Global Health, University of Washington, Seattle, WA 98104, USA
| | - Abraham Katana
- United States Centers for Disease Control and Prevention (CDC), Nairobi 00202, Kenya
| | - Lucy Nganga
- United States Centers for Disease Control and Prevention (CDC), Nairobi 00202, Kenya
| | - Grace John-Stewart
- Department of Global Health, University of Washington, Seattle, WA 98104, USA
- Department of Medicine, University of Washington, Seattle, WA 98195, USA
- Department of Epidemiology, University of Washington, Seattle, WA 98195, USA
| | - Christine J. McGrath
- Department of Global Health, University of Washington, Seattle, WA 98104, USA
- University of Texas Medical Branch, Galveston, TX 77555, USA
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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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Chen HL, Lee CN, Chang CH, Ni YH, Shyu MK, Chen SM, Hu JJ, Lin HH, Zhao LL, Mu SC, Lai MW, Lee CL, Lin HM, Tsai MS, Hsu JJ, Chen DS, Chan KA, Chang MH. Efficacy of maternal tenofovir disoproxil fumarate in interrupting mother-to-infant transmission of hepatitis B virus. Hepatology 2015; 62:375-386. [PMID: 25851052 DOI: 10.1002/hep.27837] [Citation(s) in RCA: 195] [Impact Index Per Article: 19.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/02/2014] [Accepted: 04/04/2015] [Indexed: 12/25/2022]
Abstract
UNLABELLED The efficacy and safety of maternal tenofovir disoproxil fumarate (TDF) in reducing mother-to-infant hepatitis B virus (HBV) transmissions is not clearly understood. We conducted a prospective, multicenter trial and enrolled 118 hepatitis B surface antigen (HBsAg)- and hepatitis B e antigen-positive pregnant women with HBV DNA ≥7.5 log10 IU/mL. The mothers received no medication (control group, n = 56, HBV DNA 8.22 ± 0.39 log10 IU/mL) or TDF 300 mg daily (TDF group, n = 62, HBV DNA 8.18 ± 0.47 log10 IU/mL) from 30-32 weeks of gestation until 1 month postpartum. Primary outcome was infant HBsAg at 6 months old. At delivery, the TDF group had lower maternal HBV DNA levels (4.29 ± 0.93 versus 8.10 ± 0.56 log10 IU/mL, P < 0.0001). Of the 121/123 newborns, the TDF group had lower rates of HBV DNA positivity at birth (6.15% versus 31.48%, P = 0.0003) and HBsAg positivity at 6 months old (1.54% versus 10.71%, P = 0.0481). Multivariate analysis revealed that the TDF group had lower risk (odds ratio = 0.10, P = 0.0434) and amniocentesis was associated with higher risk (odds ratio 6.82, P = 0.0220) of infant HBsAg positivity. The TDF group had less incidence of maternal alanine aminotransferase (ALT) levels above two times the upper limit of normal for ≥3 months (3.23% versus 14.29%, P = 0.0455), a lesser extent of postpartum elevations of ALT (P = 0.007), and a lower rate of ALT over five times the upper limit of normal (1.64% versus 14.29%, P = 0.0135) at 2 months postpartum. Maternal creatinine and creatinine kinase levels, rates of congenital anomaly, premature birth, and growth parameters in infants were comparable in both groups. At 12 months, one TDF-group child newly developed HBsAg positivity, presumably due to postnatal infection and inefficient humoral responses to vaccines. CONCLUSIONS Treatment with TDF for highly viremic mothers decreased infant HBV DNA at birth and infant HBsAg positivity at 6 months and ameliorated maternal ALT elevations. (Hepatology 2015;62:375-386.
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Affiliation(s)
- Huey-Ling Chen
- Departments of Pediatrics, National Taiwan University College of Medicine and Hospital, Taipei, Taiwan
- Medical Education and Bioethics, National Taiwan University College of Medicine and Hospital, Taipei, Taiwan
- Hepatitis Research Center, National Taiwan University College of Medicine and Hospital, Taipei, Taiwan
| | - Chien-Nan Lee
- Obstetrics and Gynecology, National Taiwan University College of Medicine and Hospital, Taipei, Taiwan
| | - Chin-Hao Chang
- Medical Research, National Taiwan University College of Medicine and Hospital, Taipei, Taiwan
| | - Yen-Hsuan Ni
- Departments of Pediatrics, National Taiwan University College of Medicine and Hospital, Taipei, Taiwan
| | - Ming-Kwang Shyu
- Hepatitis Research Center, National Taiwan University College of Medicine and Hospital, Taipei, Taiwan
| | - Shih-Ming Chen
- Departments of Obstetrics and Gynecology, Taiwan Adventist Hospital, Taipei, Taiwan
| | - Jen-Jan Hu
- Pediatrics, Taiwan Adventist Hospital, Taipei, Taiwan
| | - Hans Hsienhong Lin
- Departments of Internal Medicine, Buddhist Tzu-Chi General Hospital, Taipei, Taiwan
| | - Lu-Lu Zhao
- Pediatrics, Buddhist Tzu-Chi General Hospital, Taipei, Taiwan
| | - Shu-Chi Mu
- Department of Pediatrics, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan
| | - Ming-Wei Lai
- Departments of Pediatrics, Linkou Chang Gung Memorial Hospital, Linkou, Taiwan
| | - Chyi-Long Lee
- Obstetrics and Gynecology, Linkou Chang Gung Memorial Hospital, Linkou, Taiwan
| | - Hsien-Ming Lin
- Department of Obstetrics and Gynecology, Far Eastern Memorial Hospital, New Taipei City, Taiwan
| | - Ming-Song Tsai
- Department of Obstetrics and Gynecology, Cathay General Hospital, Taipei, Taiwan
| | - Jenn-Jeih Hsu
- Department of Obstetrics and Gynecology, Taipei Chang Gung Memorial Hospital, Taipei, Taiwan
| | - Ding-Shinn Chen
- Hepatitis Research Center, National Taiwan University College of Medicine and Hospital, Taipei, Taiwan
- Internal Medicine, National Taiwan University College of Medicine and Hospital, Taipei, Taiwan
- Genomics Research Center, Academia Sinica, Nankang, Taiwan
| | - K Arnold Chan
- Medical Research, National Taiwan University College of Medicine and Hospital, Taipei, Taiwan
| | - Mei-Hwei Chang
- Departments of Pediatrics, National Taiwan University College of Medicine and Hospital, Taipei, Taiwan
- Hepatitis Research Center, National Taiwan University College of Medicine and Hospital, Taipei, Taiwan
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