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Zhong W, Zheng J, Wang C, Shi L, He Y, Zhao Y, Chen T. Development and validation of a multivariable nomogram predictive of hepatitis B e antigen seroconversion after pregnancy in hepatitis B virus-infected mothers. Front Med (Lausanne) 2024; 11:1428569. [PMID: 39497841 PMCID: PMC11532139 DOI: 10.3389/fmed.2024.1428569] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2024] [Accepted: 10/07/2024] [Indexed: 11/07/2024] Open
Abstract
Background and aims Current guidelines are controversial regarding the continuation of nucleos(t)ide analogues (NAs) therapy after delivery in Hepatitis B virus (HBV)-infected pregnant women. The postpartum period may be an opportune moment for achieving hepatitis B e antigen (HBeAg) seroconversion earlier with constant NAs therapy due to the restoration of immune function after delivery. We investigated prenatal and pregnant factors associated with HBeAg seroconversion after pregnancy and developed a nomogram to predict HBeAg seroconversion rates, aiding decision-making for optimal management in women. Methods We retrospectively included 489 HBeAg-positive mothers as the training cohort from January 2014 to December 2018 and prospectively enrolled 94 patients as the external validation cohort from January 2019 to December 2021 at the First Affiliated Hospital of Xi'an Jiaotong University. In the training cohort, independent predictors were identified using the least absolute shrinkage and selection operator (LASSO) regression algorithm. Subsequently, multivariate logistic regression was employed to establish the nomogram. Model performance was assessed using the area under the receiver operating characteristic curve (AUC), calibration plots, and decision curve analysis (DCA). Both discrimination and calibration were evaluated through bootstrapping with 1,000 resamples. The external validation cohort was subsequently used to validate the nomogram. Results Factors such as pregnancy hepatitis flare (OR: 5.122, 95% CI: 2.725-9.928, p < 0.001), NAs therapy after delivery (OR: 15.051, 95% CI: 6.954-37.895, p: <0.001), hepatitis B surface antigen (HBsAg) (OR: 0.549, 95% CI: 0.366-0.812, p: 0.003) and HBV DNA level at delivery (OR: 0.785, 95% CI: 0.619-0.986, p: 0.041) were included in the final risk model. The AUC in the training set was 0.873 (95% CI: 0.839-0.904). The calibration curve of the nomogram closely resembled the ideal diagonal line. DCA showed a significantly better net benefit in the model. External validation also confirmed the reliability of the prediction nomogram. The AUC in the external validation set was 0.889 (95% CI: 0.801-0.953). The calibration curve for the external validation set was in close proximity to the ideal diagonal line. DCA also demonstrated a significant net benefit associated with the predictive model, consistent with the findings in the training set. Finally, the nomogram has been translated into an online risk calculator that is freely available to the public (https://wendyzhong.shinyapps.io/DynNomapp/). Conclusion We developed a nomogram based on prenatal and pregnant factors to estimate HBeAg seroconversion after delivery in women. This tool provides clinicians with a precise and effective way to identify individuals likely to undergo HBeAg seroconversion postpartum, aiding in decision-making for optimal management.
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Affiliation(s)
- Wenting Zhong
- Department of Infectious Disease, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
| | - Jie Zheng
- Department of Radiology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
| | - Che Wang
- Department of Radiology Oncology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
| | - Lei Shi
- Department of Infectious Disease, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
| | - Yingli He
- Department of Infectious Disease, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
| | - Yingren Zhao
- Department of Infectious Disease, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
| | - Tianyan Chen
- Department of Infectious Disease, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
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Chen HL, Lee CN, Chang CH, Lai MW, Tsai MC, Mu SC, Liu CJ, Shih JC, Wen WH, Hu RT, Huang CP, Hu KC, Chen CP, Lee CL, Chien RN, Chang KC, Hsu HY, Lee CC, Ni YH, Chang MH. Tenofovir alafenamide or tenofovir disoproxil fumarate in pregnancy to prevent HBV transmission: Maternal ALT trajectory and infant outcomes. Liver Int 2024; 44:1422-1434. [PMID: 38456620 DOI: 10.1111/liv.15873] [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: 06/14/2023] [Revised: 01/18/2024] [Accepted: 02/08/2024] [Indexed: 03/09/2024]
Abstract
BACKGROUND The use of antiviral agents, specifically tenofovir disoproxil fumarate (TDF), in pregnant women to prevent mother-to-child HBV transmission is a key step towards hepatitis elimination. However, data on using tenofovir alafenamide (TAF) is insufficient. The frequent occurrence of postpartum ALT flares may impact the clinical implementation. METHODS The maternal and infant outcomes were compared in multi-centre trials of high viral load HBsAg/HBeAg+ pregnant women receiving TAF or TDF from the third trimester until 2 weeks postpartum with intensive follow-ups. To explore the dynamic pre- and postpartum changes in ALT levels, we used a group-based trajectory model for analysing data of 332 women from three prospective studies. RESULTS After treatment, the maternal HBV DNA levels significantly decreased from baseline to delivery: 7.87 ± 0.59 to 3.99 ± 1.07 Log10 IU/mL TAF (n = 78) and 8.30 ± 0.36 to 4.47 ± 0.86 Log10 IU/mL (TDF, n = 53), with viral load reductions of 3.87 versus 3.83 Log10 IU/mL. The HBsAg-positive rates among 12-month-old infants were 1.28% (1/78) versus 1.82% (1/55) respectively (p = 1.00). Of the TAF or TDF-treated mothers, 25.64% versus 16.98% experienced ALT > 2X ULN, and 11.54% versus 1.89% received extended antiviral treatment. Our model revealed four distinct ALT patterns: stable ALT (87.2%), moderate (8.0%) or marked (2.4%) postpartum flares, or prepartum elevations (2.4%). CONCLUSIONS TAF effectively reduces mother-to-child HBV transmission, but prophylaxis failure still occurred in few cases. Postpartum ALT flares are common in women receiving TAF or TDF during pregnancy. Approximately 12.8% of mothers may require extended postpartum antiviral treatment. CLINICAL TRIAL NUMBER NCT03695029 (ClinicalTrials.gov).
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Affiliation(s)
- Huey-Ling Chen
- Department of Pediatrics, National Taiwan University College of Medicine and Children's Hospital, Taipei, Taiwan
- Department and Graduate Institute of Medical Education and Bioethics, National Taiwan University College of Medicine, Taipei, Taiwan
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Chien-Nan Lee
- Department of Obstetrics and Gynecology, National Taiwan University College of Medicine and Hospital, Taipei, Taiwan
| | - Chin-Hao Chang
- Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan
| | - Ming-Wei Lai
- Division of Pediatric Gastroenterology, Department of Pediatrics, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan
- Liver Research Center, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan
| | - Ming-Chieh Tsai
- Department of Internal Medicine, Hsinchu Cathay General Hospital, Hsinchu City, Taiwan
| | - Shu-Chi Mu
- Department of Pediatrics, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan
| | - Chun-Jen Liu
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
- Internal Medicine, National Taiwan University College of Medicine and Hospital, Taipei, Taiwan
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Jin-Chung Shih
- Department of Obstetrics and Gynecology, National Taiwan University College of Medicine and Hospital, Taipei, Taiwan
| | - Wan-Hsin Wen
- Department of Pediatrics, Cardinal Tien Hospital, New Taipei City, Taiwan
- School of Medicine, College of Medicine, Fu-Jen Catholic University, New Taipei City, Taiwan
| | - Rui-Ting Hu
- Department of Internal Medicine, Cathay General Hospital, Taipei, Taiwan
| | - Chun-Pin Huang
- Department of Pediatrics, Hsinchu Cathay General Hospital, Hsinchu City, Taiwan
| | - Kuang-Chun Hu
- Department of Internal Medicine, MacKay Memorial Hospital, Taipei, Taiwan
| | - Chie-Pein Chen
- Department of Obstetrics & Gynecology, MacKay Memorial Hospital, Taipei, Taiwan
| | - Chyi-Long Lee
- Department of Obstetrics & Gynecology, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan
| | - Rong-Nan Chien
- Liver Research Center, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan
| | - Kai-Chi Chang
- Department of Pediatrics, National Taiwan University College of Medicine and Children's Hospital, Taipei, Taiwan
| | - Hong-Yuan Hsu
- Department of Pediatrics, National Taiwan University College of Medicine and Children's Hospital, Taipei, Taiwan
- Department and Graduate Institute of Medical Education and Bioethics, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Chien-Chang Lee
- Department of Emergency Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Center of Intelligent Healthcare, National Taiwan University Hospital, Taipei, Taiwan
| | - Yen-Hsuan Ni
- Department of Pediatrics, National Taiwan University College of Medicine and Children's Hospital, Taipei, Taiwan
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Mei-Hwei Chang
- Department of Pediatrics, National Taiwan University College of Medicine and Children's Hospital, Taipei, Taiwan
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
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Chen Y, Mak LY, Tang MH, Yang J, Chow CB, Tan AM, Lyu T, Wu J, Huang Q, Huang HB, Cheung KS, Yuen MF, Seto WK. Immediate postpartum cessation of tenofovir did not increase risk of virological or clinical relapse in highly viremic pregnant mothers with chronic hepatitis B infection. JHEP Rep 2024; 6:101050. [PMID: 38699531 PMCID: PMC11063518 DOI: 10.1016/j.jhepr.2024.101050] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/29/2023] [Revised: 02/16/2024] [Accepted: 02/21/2024] [Indexed: 05/05/2024] Open
Abstract
Background & Aims Peripartum prophylaxis (PP) with tenofovir disoproxil fumarate (TDF) is the standard of care to prevent mother-to-child transmission of chronic hepatitis B (CHB) infection in mothers who are highly viremic. We investigated the maternal and infant outcomes in a large Chinese cohort of TDF-treated CHB pregnant participants. Methods In this prospective study, treatment-naive mothers with CHB and highly viremic (HBV DNA ≥200,000 IU/ml) but without cirrhosis were treated with TDF at 24-28 weeks of pregnancy. In accordance with Chinese CHB guidelines, TDF was stopped at delivery or ≥4 weeks postpartum. Serum HBV DNA and alanine aminotransferase were monitored every 6-8 weeks to determine virological relapse (VR). Infants received standard neonatal immunization, and HBV serology was checked at 7-12 months of age. Results Among 330 participants recruited (median age 30, 82.7% HBeAg+, median HBV DNA 7.82 log IU/ml), TDF was stopped at delivery in 66.4% and at ≥4 weeks in 33.6%. VR was observed in 98.3%, among which 11.6% were retreated with TDF. Timing of TDF cessation did not alter the risk of VR (99.0 vs. 96.9%), clinical relapse (19.5 vs. 14.3%), or retreatment (12.6 vs. 10.1%) (all p > 0.05). A similar proportion of patients developed alanine aminotransferase flare five times (1.1 vs. 2.1%; p = 0.464) and 10 times (0.5 vs. 0%; p = 0.669) above the upper limit of normal (ULN) in the early withdrawal and late withdrawal groups, respectively. No infants developed HBsAg-positivity. Conclusions PP-TDF and neonatal immunization were highly effective in preventing mother-to-child transmission of HBV in mothers who are highly viremic. Timing of cessation of PP-TDF did not affect the risk of VR or retreatment. Impact and Implications In pregnant mothers with chronic hepatitis B infection who are started on peripartum tenofovir to prevent mother-to-child-transmission (MTCT), the optimal timing for antiviral withdrawal during the postpartum period remains unknown. This prospective study demonstrates that stopping tenofovir immediately at delivery, compared with longer treatment duration of tenofovir, did not lead to an increased risk of virological relapse, retreatment, or transmission of the virus to the baby. Shortening the duration of peripartum antiviral prophylaxis from 12 weeks to immediately after delivery can be considered. The immediate withdrawal of peripartum tenofovir, combined with standard neonatal immunization schemes, is 100% effective in preventing MTCT among pregnant mothers with CHB who are highly viremic, with a high rate of vaccine response in infants.
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Affiliation(s)
- Yu Chen
- Department of Medicine, The University of Hong Kong – Shenzhen Hospital, Shenzhen, China
| | - Lung-Yi Mak
- Department of Medicine, The University of Hong Kong, Hong Kong, China
- State Key Laboratory of Liver Research, The University of Hong Kong, Hong Kong, China
| | - Mary H.Y. Tang
- Department of Obstetrics and Gynaecology, The University of Hong Kong, Hong Kong, China
- Department of Obstetrics and Gynecology, The University of Hong Kong – Shenzhen Hospital, Shenzhen, China
| | - Jingyi Yang
- Department of Obstetrics and Gynecology, The University of Hong Kong – Shenzhen Hospital, Shenzhen, China
| | - Chun Bong Chow
- Department of Pediatrics, The University of Hong Kong – Shenzhen Hospital, Shenzhen, China
| | - Ai-Ming Tan
- Department of Medicine, The University of Hong Kong – Shenzhen Hospital, Shenzhen, China
| | - Tao Lyu
- Department of Medicine, The University of Hong Kong – Shenzhen Hospital, Shenzhen, China
| | - Juan Wu
- Department of Medicine, The University of Hong Kong – Shenzhen Hospital, Shenzhen, China
| | - Qingjuan Huang
- Department of Medicine, The University of Hong Kong – Shenzhen Hospital, Shenzhen, China
| | - Hai-Bo Huang
- Department of Pediatrics, The University of Hong Kong – Shenzhen Hospital, Shenzhen, China
| | - Ka-Shing Cheung
- Department of Medicine, The University of Hong Kong – Shenzhen Hospital, Shenzhen, China
- Department of Medicine, The University of Hong Kong, Hong Kong, China
| | - Man-Fung Yuen
- Department of Medicine, The University of Hong Kong – Shenzhen Hospital, Shenzhen, China
- Department of Medicine, The University of Hong Kong, Hong Kong, China
- State Key Laboratory of Liver Research, The University of Hong Kong, Hong Kong, China
| | - Wai-Kay Seto
- Department of Medicine, The University of Hong Kong – Shenzhen Hospital, Shenzhen, China
- Department of Medicine, The University of Hong Kong, Hong Kong, China
- State Key Laboratory of Liver Research, The University of Hong Kong, Hong Kong, China
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You H, Wang F, Li T, Xu X, Sun Y, Nan Y, Wang G, Hou J, Duan Z, Wei L, Jia J, Zhuang H. Guidelines for the Prevention and Treatment of Chronic Hepatitis B (version 2022). J Clin Transl Hepatol 2023; 11:1425-1442. [PMID: 37719965 PMCID: PMC10500285 DOI: 10.14218/jcth.2023.00320] [Citation(s) in RCA: 29] [Impact Index Per Article: 14.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/09/2023] [Revised: 08/02/2023] [Accepted: 08/03/2023] [Indexed: 09/19/2023] Open
Abstract
To facilitate the achieving of the goal of "eliminating viral hepatitis as a major public health threat by 2030" set by the World Health Organization, the Chinese Society of Hepatology together with the Chinese Society of Infectious Diseases (both are branches of the Chinese Medical Association) organized a panel of experts and updated the guidelines for prevention and treatment of chronic hepatitis B in China (version 2022). With the support of available evidence, this revision of the guidelines focuses on active prevention, large scale testing, and expansion of therapeutic indication of chronic hepatitis B with the aim of reducing the hepatitis B related disease burden.
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Affiliation(s)
- Hong You
- Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Fusheng Wang
- The Fifth Medical Center of PLA General Hospital, Beijing, China
| | - Taisheng Li
- Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
| | - Xiaoyuan Xu
- Peking University First Hospital, Beijing, China
| | - Yameng Sun
- Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Yuemin Nan
- Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, China
| | | | - Jinlin Hou
- Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China
| | - Zhongping Duan
- Beijing You-An Hospital, Capital Medical University, Beijing, China
| | - Lai Wei
- Tsinghua Changgung Hospital, Tsinghua University, Beijing, China
| | - Jidong Jia
- Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Hui Zhuang
- Peking University Health Science Center, Beijing, China
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Aliasi-Sinai L, Worthington T, Lange M, Kushner T. Maternal-to-Child Transmission of Hepatitis B Virus and Hepatitis Delta Virus. Clin Liver Dis 2023; 27:917-935. [PMID: 37778777 DOI: 10.1016/j.cld.2023.05.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/03/2023]
Abstract
Maternal-to-child transmission of hepatitis B virus (HBV) and hepatitis delta virus (HDV) can lead to the risk of progressive liver disease in infants, but fortunately effective interventions exist to decrease transmission. Counseling on the risk of maternal-to-child transmission, care pathways to decrease transmission, and the implications of HBV and HDV on pregnancy outcomes are the key components of caring for pregnant people living with HBV and HDV.
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Affiliation(s)
| | - Theresa Worthington
- Division of Liver Diseases, Icahn School of Medicine at Mount Sinai, New York, USA
| | - Marcia Lange
- Icahn School of Medicine at Mount Sinai, New York, USA
| | - Tatyana Kushner
- Division of Liver Diseases, Icahn School of Medicine at Mount Sinai, New York, USA.
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Ju Y, Han G, Zhang P, Xu J, Chen C, Jiang H, Yuan D, Ye X, Zhou G. Staging and clinical characteristics of pregnant women with chronic hepatitis B virus infection: A retrospective cohort study from Nanjing, China. J Obstet Gynaecol Res 2023; 49:2427-2435. [PMID: 37515503 DOI: 10.1111/jog.15753] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2023] [Accepted: 07/16/2023] [Indexed: 07/31/2023]
Abstract
AIM To investigate the immune status of Chinese chronic hepatitis B (CHB) pregnant women and their clinical characteristics. METHODS About 1544 CHB pregnant women without antiviral therapy from 2013 to 2018 were selected from the hospital records. The definition of immune status is based on American Association for the Study of Liver Diseases (AASLD) 2018 Hepatitis B Guidance, and those who did not meet any criteria of the immune status were referred to in the gray zones (GZ). RESULTS There were 284 patients in the immune-tolerance phase, 72 patients in the HBeAg-positive immune active phase, 553 patients in the inactive phase, 61 patients in the HBeAg-negative immune active phase. Of note, 574 (37.18%) patients did not fit into any of the above phases were defined as the GZ. Patients with elevated ALT had a higher rate of intrahepatic cholestasis of pregnancy (ICP). Mother to child HBV transmission was rare (only two cases) and occurred in mothers in the immune-tolerant phase. CONCLUSIONS Our data showed that more than one-third of CHB pregnant women were classified into the GZ. In standard stages, advanced age is associated with HBeAg-negative and a higher cesarean rate in the inactive phase. The incidence of ICP was higher in immune active phases, including GB and GD. The probability of mother-to-child transmission in gray zones is low.
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Affiliation(s)
- Yuhao Ju
- Department of Obstetrics and Gynecology, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing, China
| | - Guorong Han
- Department of Obstetrics and Gynecology, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing, China
| | - Ping Zhang
- Department of Obstetrics and Gynecology, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing, China
| | - Jing Xu
- Department of Obstetrics and Gynecology, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing, China
| | - Chao Chen
- Department of Obstetrics and Gynecology, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing, China
| | - Hongxiu Jiang
- Department of Obstetrics and Gynecology, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing, China
| | - Deping Yuan
- Department of Obstetrics and Gynecology, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing, China
| | - Xiajun Ye
- Department of Obstetrics and Gynecology, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing, China
| | - Guanlun Zhou
- Department of Obstetrics and Gynecology, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing, China
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Abstract
PURPOSE The purpose of this document is to describe the specific types of viral hepatitis, their implications during pregnancy, the risk of perinatal transmission, and issues related to both treatment and prevention of infection. TARGET POPULATION Pregnant or postpartum women and individuals who screen positive for viral hepatitis infection. The onset of these conditions may have predated the perinatal period or may have occurred for the first time in pregnancy or the first year postpartum. METHODS This guideline was developed using an a priori protocol in conjunction with a writing team consisting of one specialist in obstetrics and gynecology appointed by the ACOG Committee on Clinical Practice Guidelines-Obstetrics and one external subject matter expert. ACOG medical librarians completed a comprehensive literature search for primary literature within Cochrane Library, Cochrane Collaboration Registry of Controlled Trials, EMBASE, PubMed, and MEDLINE. Studies that moved forward to the full-text screening stage were assessed by two authors from the writing team based on standardized inclusion and exclusion criteria. Included studies underwent quality assessment, and a modified GRADE (Grading of Recommendations Assessment, Development, and Evaluation) evidence-to-decision framework was applied to interpret and translate the evidence into recommendation statements. RECOMMENDATIONS This Clinical Practice Guideline includes recommendations on hepatitis B virus and hepatitis C virus screening in pregnancy; prepregnancy, antepartum, intrapartum, and postpartum management for patients with hepatitis B virus infection or hepatitis C virus infection; management of accidental and occupational exposure to hepatitis B virus or hepatitis C virus in pregnant health care workers; and hepatitis A virus and hepatitis B virus vaccination in pregnancy. Recommendations are classified by strength and evidence quality. Ungraded Good Practice Points are included to provide guidance when a formal recommendation could not be made because of inadequate or nonexistent evidence.
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Bhattacharya D, Tierney C, Butler K, Kiweewa FM, Moodley D, Govender V, Vhembo T, Mohtashemi N, Ship H, Dula D, George K, Chaktoura N, Glenn Fowler M, Peters MG, Currier JS. Comparison of Antiretroviral Therapies in Pregnant Women Living With Human Immunodeficiency Virus and Hepatitis B Virus: A Randomized Controlled Trial. Obstet Gynecol 2023; 142:613-624. [PMID: 37535953 PMCID: PMC10527604 DOI: 10.1097/aog.0000000000005302] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2022] [Accepted: 04/04/2023] [Indexed: 08/05/2023]
Abstract
OBJECTIVE To describe the anti-hepatitis B virus (HBV) efficacy, HBeAg serologic changes, HBV perinatal transmission, and safety in pregnant women who are living with human immunodeficiency virus (HIV) and HBV co-infection who were randomized to various antiretroviral therapy (ART) regimens. METHODS The PROMISE (Promoting Maternal and Infant Survival Everywhere) trial was a multicenter randomized trial for ART-naive pregnant women with HIV infection. Women with HIV and HBV co-infection at 14 or more weeks of gestation were randomized to one of three ART arms: one without HBV treatment (group 1) and two HBV treatment arms with single (group 2) or dual anti-HBV activity (group 3). The primary HBV outcome was HBV viral load antepartum change from baseline (enrollment) to 8 weeks; safety assessments included alanine aminotransferase (ALT) level, aspartate aminotransferase (AST) level, and anemia (hemoglobin less than 10 g/dL). Primary comparison was for the HBV-active treatment arms. Pairwise comparisons applied t test and the Fisher exact tests. RESULTS Of 3,543 women, 3.9% were HBsAg-positive; 42 were randomized to group 1, 48 to group 2, and 48 to group 3. Median gestational age at enrollment was 27 weeks. Among HBV-viremic women, mean antepartum HBV viral load change at week 8 was -0.26 log 10 international units/mL in group 1, -1.86 in group 2, and -1.89 in group 3. In those who were HBeAg-positive, HBeAg loss occurred in 44.4% at delivery. Two perinatal HBV transmissions occurred in group 2. During the antepartum period, one woman (2.4%) in group 1 had grade 3 or 4 ALT or AST elevations, two women (4.2%) in group 2, and three women (6.3%) in group 3. CONCLUSION Over a short period of time, HBV DNA suppression was not different with one or two HBV-active agents. HbeAg loss occurred in a substantial proportion of participants. Perinatal transmission of HBV infection was low. Hepatitis B virus-active ART was well-tolerated in pregnancy, with few grade 3 or 4 ALT or AST elevations. CLINICAL TRIAL REGISTRATION ClinicalTrials.gov , NCT01061151.
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Affiliation(s)
| | | | | | - Flavia Matovu Kiweewa
- MU-JHU Research Collaboration, Kampala, Uganda
- Makerere University School of Public Health, Kampala, Uganda
| | | | - Vani Govender
- Caprisa -University of KwazuluNatal
- University of Kwazulu-Natal, Durban, South Africa
| | | | | | | | - Dingase Dula
- Johns Hopkins Research Project, Blantyre, Malawi
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Matthews PC, Ocama P, Wang S, El-Sayed M, Turkova A, Ford D, Torimiro J, Garcia Ferreira AC, Espinosa Miranda A, De La Hoz Restrepo FP, Seremba E, Mbu R, Pan CQ, Razavi H, Dusheiko G, Spearman CW, Hamid S. Enhancing interventions for prevention of mother-to-child- transmission of hepatitis B virus. JHEP Rep 2023; 5:100777. [PMID: 37554925 PMCID: PMC10405098 DOI: 10.1016/j.jhepr.2023.100777] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/21/2022] [Revised: 03/29/2023] [Accepted: 03/31/2023] [Indexed: 08/10/2023] Open
Abstract
Prevention of mother-to-child transmission of hepatitis B virus (HBV) infection is a cornerstone of efforts to support progress towards elimination of viral hepatitis. Current guidelines recommend maternal screening, antiviral therapy during the third trimester of high-risk pregnancies, universal and timely HBV birth dose vaccination, and post-exposure prophylaxis with hepatitis B immunoglobulin for selected neonates. However, serological and molecular diagnostic testing, treatment and HBV vaccination are not consistently deployed, particularly in many high endemicity settings, and models predict that global targets for reduction in paediatric incidence will not be met by 2030. In this article, we briefly summarise the evidence for current practice and use this as a basis to discuss areas in which prevention of mother-to-child transmission can potentially be enhanced. By reducing health inequities, enhancing pragmatic use of resources, filling data gaps, developing advocacy and education, and seeking consistent investment from multilateral agencies, significant advances can be made to further reduce vertical transmission events, with wide health, societal and economic benefits.
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Affiliation(s)
- Philippa C. Matthews
- The Francis Crick Institute, 1 Midland Road, London, NW1 1AT, UK
- Division of Infection and Immunity, University College London, Gower St, London WC1E 6BT, UK
- Department of Infection, University College London Hospitals, 235 Euston Rd, London NW1 2BU, UK
| | - Ponsiano Ocama
- Department of Medicine, Makerere University College of Health Sciences, Kampala, Uganda
| | - Su Wang
- Cooperman Barnabas Medical Center, Florham Park, NJ, USA
- Hepatitis B Foundation, Doylestown, PA, USA
| | - Manal El-Sayed
- Department of Paediatrics, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Anna Turkova
- Medical Research Council Clinical Trials Unit, University College London, 90 High Holborn, London WC1V 6LJ, UK
| | - Deborah Ford
- Medical Research Council Clinical Trials Unit, University College London, 90 High Holborn, London WC1V 6LJ, UK
| | - Judith Torimiro
- Chantal Biya International Reference Centre for Research on Prevention and Management of HIV/AIDS (CIRCB), Yaounde, Cameroon
- Faculty of Medicine and Biomedical Sciences, University of Yaounde, Yaounde, Cameroon
| | - Ana Cristina Garcia Ferreira
- Ministry of Health, Health Surveillance Department, Department of Chronic Diseases and Sexually Transmitted Infections, SRTVN Quadra 701, Lote D, PO700 Building, CEP: 70719-040, Brasília/DF, Brazil
| | - Angélica Espinosa Miranda
- Ministry of Health, Health Surveillance Department, Department of Chronic Diseases and Sexually Transmitted Infections, SRTVN Quadra 701, Lote D, PO700 Building, CEP: 70719-040, Brasília/DF, Brazil
| | | | - Emmanuel Seremba
- Department of Medicine, Makerere University College of Health Sciences, Kampala, Uganda
| | - Robinson Mbu
- Faculty of Medicine and Biomedical Sciences, University of Yaounde, Yaounde, Cameroon
| | - Calvin Q. Pan
- Division of Gastroenterology and Hepatology, NYU Langone Health, NYU Grossman School of Medicine, NY, USA
| | - Homie Razavi
- Center for Disease Analysis Foundation, 1120 W South Boulder Rd Suite 102, Lafayette, CO 80026, USA
| | - Geoffrey Dusheiko
- Liver Unit, King’s College Hospital, Denmark Hill, London SE5 9RS, UK
| | - C. Wendy Spearman
- Division of Hepatology, Department of Medicine, Faculty of Health Sciences, University of Cape Town, South Africa
| | - Saeed Hamid
- Department of Medicine, Aga Khan University, Karachi, Pakistan
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10
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Li M, Sun F, Bi X, Lin Y, Yang L, Jiang T, Deng W, Lu Y, Zhang L, Yi W, Xie Y. Effects of antiviral therapy and drug withdrawal on postpartum hepatitis in pregnant women with chronic HBV infection. Hepatol Int 2023; 17:42-51. [PMID: 36109430 DOI: 10.1007/s12072-022-10412-w] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/03/2022] [Accepted: 08/13/2022] [Indexed: 02/07/2023]
Abstract
OBJECTIVE To investigate the effect of antiviral therapy and drug withdrawal on the incidence of hepatitis B after delivery in pregnant women with chronic hepatitis B virus (CHB) infection who received tenofovir disoproxil fumarate (TDF) treatment. METHODS Eligible CHB pregnant women were enrolled, and received TDF at 32 weeks gestation. The drug was stopped immediately or at 6 weeks after delivery. The HBV biomarkers and clinical biochemical parameters were monitored during gestation and 24 weeks after delivery. RESULTS There were 264 women completed the observation, including 96 untreated subjects in control group. Among 168 treated subjects, 131 cases stopped drug immediately after delivery and 37 cases delayed the drug withdrawal at 6 weeks after delivery. The incidence of postpartum hepatitis in control, immediate drug withdrawal, and delayed drug withdrawal were 28.1% (27/96), 23.7% (31/131), and 24.3% (9/37), showing no significant difference (χ2 = 0.607, p = 0.738). No factor was found to be associated with the occurrence of postpartum hepatitis. It's noteworthy that 96.3% of postpartum hepatitis in control group and 92.3% of postpartum hepatitis in immediate drug withdrawal group occurred within 12 weeks after delivery. While in delayed drug withdrawal group, the rate of postpartum hepatitis occurred within 12 weeks after delivery was 77.7%. CONCLUSION Withdrawing antiviral drug immediately or at 6 weeks after delivery did not affect the incidence of postpartum hepatitis in CHB women, but delaying drug withdrawal might delay the onset of postpartum hepatitis. CLINICAL TRIAL REGISTRATION NUMBER NCT03214302.
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Affiliation(s)
- Minghui Li
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, China.,Department of Hepatology Division 2, Peking University Ditan Teaching Hospital, Beijing, 100015, China
| | - Fangfang Sun
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, China
| | - Xiaoyue Bi
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, China
| | - Yanjie Lin
- Department of Hepatology Division 2, Peking University Ditan Teaching Hospital, Beijing, 100015, China
| | - Liu Yang
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, China
| | - Tingting Jiang
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, China
| | - Wen Deng
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, China
| | - Yao Lu
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, China
| | - Lu Zhang
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, China
| | - Wei Yi
- Department of Gynecology and Obstetrics, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, China.
| | - Yao Xie
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, China. .,Department of Hepatology Division 2, Peking University Ditan Teaching Hospital, Beijing, 100015, China.
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11
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Efficacy and safety of long-term postpartum antiviral therapy in hepatitis B virus-infected mothers receiving prophylactic tenofovir disoproxil fumarate treatment. Eur J Gastroenterol Hepatol 2023; 35:212-218. [PMID: 36574312 DOI: 10.1097/meg.0000000000002476] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
OBJECTIVES This study aimed to evaluate the efficacy and safety of long-term postpartum tenofovir disoproxil fumarate (TDF) therapy in hepatitis B virus (HBV)-infected mothers with high viral load. METHODS In this retrospective cohort study, HBV-infected mothers with HBV DNA>2 × 10 5 IU/mL who initiated TDF prophylaxis treatment during pregnancy were divided into TDF continuation and discontinuation groups according to whether they stopped TDF treatment within 3 months after birth or not. Virological and biochemical markers were collected before TDF treatment, antepartum and postpartum. RESULTS In 131 women followed for a median of 18 months postpartum, alanine aminotransferase (ALT) abnormality rate was significantly lower in TDF continuation group vs. discontinuation group (39.4% vs. 56.9%, P = 0.045), and continuous TDF therapy in postpartum was independently associated with lower risk of ALT flares [OR = 0.308, 95% confidence interval (CI), 0.128-0.742; P = 0.009]. Long-term postpartum TDF treatment can promote the decline of hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) levels, but the HBeAg seroconversion rate in two groups was not significant (15.5% vs. 11.7%, P = 0.541). There were no statistical differences in bone metabolism markers between two groups ( P > 0.05). Compared with the TDF discontinuation group, TDF continuation group had a significantly lower estimated glomerular filtration rate level and higher creatinine level in postpartum but within normal ranges ( P < 0.05). CONCLUSIONS For pregnant women who received prophylactic TDF treatment, long-term TDF therapy continued in postpartum can reduce the risk of ALT flares and promote the rapid decline of HBeAg and HBsAg levels.
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12
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Thilakanathan C, Kayes T, Di Girolamo J, Nguyen V, Glass A, Manandhar S, Lawler J, Meredith C, Maley M, Lloyd A, Levy MT. Predicting hepatitis B e Antigen seroconversion after pregnancy-The SydPregScore. Liver Int 2023; 43:69-76. [PMID: 35861306 PMCID: PMC10087847 DOI: 10.1111/liv.15372] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/14/2022] [Revised: 06/30/2022] [Accepted: 07/19/2022] [Indexed: 01/04/2023]
Abstract
BACKGROUND AND AIMS Achieving Hepatitis B e antigen seroconversion (HBeAg SC) at an earlier age confers a better prognosis. We examined baseline and post-partum factors associated with HBeAg SC after pregnancy. We developed a tool, the SydPregScore, to estimate the likelihood of HBeAg SC in the years after pregnancy. METHODS A retrospective analysis of an HBeAg-positive pregnant cohort was conducted. Variables including baseline age, parity, alanine aminotransferase level, HBV viral load, quantitative HBsAg, use of antiviral therapy and post-partum flare were collected. Univariate and multivariate Cox regression analyses to determine predictors of HBeAg SC and develop a predictor score were performed. RESULTS We analysed HBeAg SC rates in 220 pregnancies to 149 HBeAg-positive women from 2006 to 2019. At baseline, their median age was 33 (IQR 29-37), ALT 23 U/L (IQR 17-33) and viral load 8 log10 IU/mL (IQR 6.3-8.2 log10 IU/mL). The majority (133/198, 67.2%) received short-course antiviral therapy to prevent mother-to-child transmission, and 109/192 (56.8%) had a post-partum flare. HBeAg SC occurred in 74/220 (33.6%) after pregnancy (median follow-up 814 days, IQR 405-1531). Multivariate analysis identified baseline viral load <8 log10 IU/mL (HR 2.426 [1.224-4.809], p = .011), baseline ALT ≥2 ULN (HR 2.726 [1.299-5.721], p = .008) and age <35 (HR 2.859 [1.255-6.513], p = .012) to be positive predictors of HBeAg SC. The 'SydPreg Score' estimated the probability of HBeAg SC at 2000 days as 10%, 30%, 70% and 80% for 0, 1, 2, and 3 predictors respectively. CONCLUSION The SydPreg Score allows the prediction of HBeAg SC in the years after pregnancy. Even in those without elevated ALT, age <35 and viral load <8 log10 IU/mL can identify women with a good chance of subsequent HBeAg SC. Those without a chance may benefit from viral suppression.
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Affiliation(s)
- Cynthuja Thilakanathan
- Department of Gastroenterology and Hepatology, Liverpool Hospital, Sydney, Australia.,South Western Sydney Clinical School, University of New South Wales Sydney, Liverpool, Sydney, Australia
| | - Tahrima Kayes
- Department of Gastroenterology and Hepatology, Liverpool Hospital, Sydney, Australia
| | - Julia Di Girolamo
- Department of Gastroenterology and Hepatology, Liverpool Hospital, Sydney, Australia
| | - Vi Nguyen
- South Western Sydney Clinical School, University of New South Wales Sydney, Liverpool, Sydney, Australia
| | - Anne Glass
- Department of Gastroenterology and Hepatology, Liverpool Hospital, Sydney, Australia
| | - Sicha Manandhar
- Department of Gastroenterology and Hepatology, Liverpool Hospital, Sydney, Australia
| | - Joseph Lawler
- Department of Gastroenterology and Hepatology, Bankstown Hospital, Sydney, Australia
| | - Chris Meredith
- Department of Gastroenterology and Hepatology, Bankstown Hospital, Sydney, Australia
| | - Michael Maley
- South Western Sydney Clinical School, University of New South Wales Sydney, Liverpool, Sydney, Australia.,Sydney South West Pathology Service, Liverpool Hospital, Sydney, Australia
| | - Andrew Lloyd
- The Kirby Institute, University of New South Wales Sydney, Sydney, Australia
| | - Miriam T Levy
- Department of Gastroenterology and Hepatology, Liverpool Hospital, Sydney, Australia.,South Western Sydney Clinical School, University of New South Wales Sydney, Liverpool, Sydney, Australia
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13
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Mendlowitz AB, Feld JJ, Biondi MJ. Hepatitis B and C in Pregnancy and Children: A Canadian Perspective. Viruses 2022; 15:91. [PMID: 36680130 PMCID: PMC9863739 DOI: 10.3390/v15010091] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2022] [Revised: 12/24/2022] [Accepted: 12/27/2022] [Indexed: 12/30/2022] Open
Abstract
In 2016, the World Health Organization released a plan to eliminate viral hepatitis as a public health threat by 2030. For Canada to achieve the recommended decreases in HBV- and HCV-related new diagnoses and deaths, an increase in services is urgently required. Identifying those at risk of, or who have acquired HBV and HCV, remains a challenge, especially with the emergence of new priority populations such as pregnant persons and children. Importantly, prenatal, and pediatric care are times when individuals are often already engaged with the healthcare system, leading to the potential for opportunistic or co-localized care and interventions. At present, Canada may not be maximizing all available virologic tools that could lead to increases in prevention, identification, improved management, or even cure. Here, we describe the continuum of care that includes preconception, prenatal, postpartum, and pediatric stages; and identify current global and Canadian recommendations, findings, and opportunities for improvement.
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Affiliation(s)
- Andrew B. Mendlowitz
- Viral Hepatitis Care Network, Toronto Centre for Liver Disease, University Health Network, Toronto, ON M5G 2C4, Canada
| | - Jordan J. Feld
- Viral Hepatitis Care Network, Toronto Centre for Liver Disease, University Health Network, Toronto, ON M5G 2C4, Canada
| | - Mia J. Biondi
- Viral Hepatitis Care Network, Toronto Centre for Liver Disease, University Health Network, Toronto, ON M5G 2C4, Canada
- School of Nursing, York University, Toronto, ON M3J 1P3, Canada
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14
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Liaw YF. Hepatitis B flare: the good, the bad and the ugly. Expert Rev Gastroenterol Hepatol 2022; 16:1043-1051. [PMID: 36476208 DOI: 10.1080/17474124.2022.2156338] [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: 12/12/2022]
Abstract
INTRODUCTION Hepatitis B flare, defined as an event of abrupt ALT elevation to >5x ULN, is a frequent episode during the natural course or during/after antiviral therapy of chronic HBV infection, in both HBeAg-positive and HBeAg-negative patients with chronic hepatitis B or liver cirrhosis. AREAS COVERED The definition, pathogenesis, clinical presentation, and management of hepatitis B flares in the published literature were reviewed. Hepatitis B flares have been considered as a result of the robust immune response of the patient to an upsurging HBV/HBV-antigen(s). 'Host-dominating flares,' reflect effective immune response, may resolve with ALT normalization and decline of HBV/ antigen(s). Contradictorily, 'virus-dominating flares,' reflect ineffective immune response, are usually followed by persistent/intermittent hepatitis and may even develop hepatic decompensation/failure. EXPERT OPINION Not all hepatitis B flares require antiviral therapy, and close observation with combined HBsAg/ALT kinetics along the ascending ALT during hepatitis flare may differentiate hepatitis flares for an appropriate treatment/retreatment decision. More studies are needed to verify this proposal. Further immunologic studies using multiple samples during hepatitis B flare are important to clarify the precise underlying mechanisms as the basis for further improvement in the management of hepatitis flare.
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Affiliation(s)
- Yun-Fan Liaw
- Liver Research Unit, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan, Taiwan
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15
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Wang X, Song A, Lin X, Lu J, Zheng S, Ma L, Ren S, Zheng Y, Chen X. Clinical characteristics of hepatitis flares during pregnancy and postpartum in Chinese chronic hepatitis B virus carriers—a prospective cohort study of 417 cases. Front Immunol 2022; 13:1031291. [PMID: 36311697 PMCID: PMC9606458 DOI: 10.3389/fimmu.2022.1031291] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2022] [Accepted: 09/29/2022] [Indexed: 11/30/2022] Open
Abstract
Background In China, it is common for pregnant women with a high load of hepatitis B virus (HBV) to take nucleos(t)ide analogue (NA) to prevent maternal-to-child transmission of HBV. However, the impact of NA intervention on virological and biochemical parameters in pregnant and postpartum women and the safety of drug cessation remain unclear. A prospective observational cohort was established in this study to analyze the clinical characteristics of hepatitis flares in pregnant and postpartum chronic HBV carriers, with or without NA intervention. Methods Pregnant women who were chronic HBV carriers were enrolled in this study and divided into an NA intervention group and a non-intervention group according to their preferences. Liver function, HBV DNA level, and HBV serological markers were regularly measured during pregnancy and at approximately 6 weeks, 12 weeks, 24 weeks, 36 weeks, and 48 weeks postpartum. Results A total of 417 patients were enrolled, including 303 in the NA intervention group and 114 in the non-intervention group. The incidence rates of postpartum hepatitis flares in both groups were higher than that of during pregnancy (45.7% vs 10.9%, p < 0.001; 41.2% vs 17.7%, p < 0.001). The second trimester was the peak of the incidence of flares during pregnancy and the incidence peak of postpartum flares was about 6 weeks postpartum. A total of 98% (145/148) of postpartum flares occurred within 24 weeks postpartum. After drug cessation, the incidence rate of flares was 34.1% (44/129). Conclusion In pregnant chronic HBV carriers, a certain proportion of hepatitis flares occurred during pregnancy and postpartum regardless of whether NA intervention was used, and the incidence of postpartum flares (44.6%) was significantly higher than that (12.8%) of during pregnancy. The flare incidence peaked at approximately 6 weeks postpartum, which may be the time period suitable for treatment. Since 98% of postpartum flares occurred within 24 weeks postpartum, the follow-up after drug cessation should be at least 24 weeks postpartum.
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16
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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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17
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Antiviral Therapy for Prevention of Perinatal Hepatitis B Virus Transmission Reduces the Incidence of Postpartum Hepatitis Flare. BIOMED RESEARCH INTERNATIONAL 2022; 2022:7046955. [PMID: 35860799 PMCID: PMC9293540 DOI: 10.1155/2022/7046955] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/03/2022] [Revised: 06/11/2022] [Accepted: 06/20/2022] [Indexed: 11/23/2022]
Abstract
Background: Currently, there are few studies on the effect of prophylactic anti-hepatitis B virus (HBV) therapy (AVT) for mother-to-child transmission during pregnancy on postpartum hepatitis flare (PHF) and the risk factors for postpartum hepatitis flare in women with chronic hepatitis B infection. Aim: To analyze the effect of AVT on the postpartum hepatitis flare and risk factors related to postpartum hepatitis flare. Methods: This study retrospectively enrolled hepatitis B surface antigen (HBsAg)-positive and hepatitis B e antigen (HBeAg)-positive women with HBV DNA ≥ 106 IU/mL. Six hundred fourteen pregnant women were included: 444 in the anti-HBV therapy group (T-G) and 170 in the control group (C-G). To analyze the risk factors, women with alanine aminotransferase (ALT) flare (ALT > 40 U/L) were assigned to the PHF group (PHF-G, n = 355), and all the others were assigned to a non-PHF group (NPHF-G, n = 259). Results: At 6 weeks postpartum, ALT and AST levels were higher, and ALB levels were lower in the C-G than those in T-G (P < 0.05). Also, ALT (at baseline, pregnancy 32nd and 36th, intrapartum), AST (at pregnancy 32nd and 36th week, and intrapartum), HBcAb (at baseline, intrapartum), and HBV DNA (at intrapartum) of PHF-G were significantly higher than those of NPHF-G (P < 0.05). Multivariate analysis showed that ALT (OR = 1.067, P < 0.001) and HBcAb (OR = 1.213, P ≤ 0.001) in pregnant women were risk factors for PHF. The prophylactic anti-HBV for the prevention of perinatal HBV transmission (OR = 0.357, P < 0.001) was the protective factor for PHF. Conclusion: Pregnant women with prophylactic anti-HBV during the third trimester of pregnancy had a lower incidence of postpartum hepatitis flare, especially a lower risk of serious hepatitis flare. ALT and HBcAb in pregnant women were risk factors for PHF. Women infected with HBV should be closely monitored ALT during pregnancy and postpartum.
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18
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Quan M, Liu C, Li W, Xing HC. Antiviral Therapy for a Postpartum Flare in Women with Chronic HBV Infection Shortens the ALT Recovery Time and Reduces Hepatitis Re-Flare Rates within 4 years. Can J Gastroenterol Hepatol 2022; 2022:4753267. [PMID: 35770180 PMCID: PMC9236834 DOI: 10.1155/2022/4753267] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/26/2022] [Revised: 05/11/2022] [Accepted: 06/02/2022] [Indexed: 02/07/2023] Open
Abstract
Background Few studies explored whether anti-hepatitis B virus (HBV) therapy should be initiated during postpartum hepatitis flare. Aim This study aimed to analyze the effect of anti-HBV therapy on postpartum hepatitis flare and evaluate the prognosis within 4 years postpartum. Methods This retrospective study enrolled hepatitis B surface antigen (HBsAg)-positive and hepatitis B e antigen (HBeAg)-positive pregnant women with HBV DNA ≥ 106 IU/mL. A total of 152 pregnant women were included: 103 in the prophylactic anti-HBV therapy group (PT-G) and 49 in the non-prophylactic anti-HBV therapy group (NPT-G). The women with a postpartum flare were assigned to the anti-HBV therapy group (AT-G) and non-anti-HBV therapy group (NAT-G) to analyze the effect of postpartum anti-HBV therapy on hepatitis flare. Virological and biochemical parameters were assessed. Results Taking postpartum 12 weeks as the cutoff point, the ALT recovered time for postpartum flare women is shorter in AT-G (n = 16, 42.1%) or PT-G (n = 23, 34.8%) than in NAT-G (n = 14, 23.0%; x 2 = 4.067, P=0.044) or NPT-G (n = 4, 11.1%; x 2 = 5.579, P=0.018). Taking postpartum 26 weeks as the cutoff point, the ALT recovered time is shorter in AT-G (n = 35, 57.3%) or PT-G (n = 44, 66.7%) than in NAT-G (n = 32, 84.2%; x 2 = 7.707, P=0.006) or NPT-G (n = 16, 44.4%; x 2 = 4.749, P=0.029). Postpartum flare recovery time was positively correlated with HBV DNA level at delivery [r = 0.223, P=0.025, 95%CI (0.022～0.41)]. The hepatitis re-flare rates within postpartum 4 years in AT-G (n = 3, 9.68%) is lower than that in NAT-G (n = 24, 45.4%; x 2 = 14.003, P ≤ 0.001). The HBeAg, HBsAg, HBV DNA, and ALT level at postpartum 4 years in AT-G were lower than that in NAT-G (P < 0.001). Conclusion Anti-HBV therapy for postpartum hepatitis flare of women with chronic HBV could shorten the ALT recovery time and reduce hepatitis re-flare rates within 4 years of postpartum.
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Affiliation(s)
- Min Quan
- Center of Liver Diseases Division 3, Beijing Ditan Hospital, Capital Medical University, Bejing 100015, China
- Peking University Ditan Teaching Hospital, Beijing 100015, China
| | - Cong Liu
- Department of Infectious Diseases, The Second Hospital of Shanxi Medical University, Taiyuan, Shanxi 030000, China
| | - Wei Li
- Center of Liver Diseases Division 3, Beijing Ditan Hospital, Capital Medical University, Bejing 100015, China
- Peking University Ditan Teaching Hospital, Beijing 100015, China
| | - Hui-Chun Xing
- Center of Liver Diseases Division 3, Beijing Ditan Hospital, Capital Medical University, Bejing 100015, China
- Peking University Ditan Teaching Hospital, Beijing 100015, China
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19
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Chang ML, Liaw YF. Hepatitis B Flare in Hepatitis B e Antigen-Negative Patients: A Complicated Cascade of Innate and Adaptive Immune Responses. Int J Mol Sci 2022; 23:ijms23031552. [PMID: 35163476 PMCID: PMC8836007 DOI: 10.3390/ijms23031552] [Citation(s) in RCA: 27] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2021] [Revised: 01/19/2022] [Accepted: 01/26/2022] [Indexed: 12/11/2022] Open
Abstract
Chronic hepatitis B virus (HBV) infection is a dynamic process involving interactions among HBV, hepatocytes, and the host immune system. The natural course of chronic hepatitis B (CHB) is divided into four chronological phases, including the hepatitis B e antigen (HBeAg)-positive and HBeAg-negative phases. During HBV flare, alanine aminotransferase (ALT) levels abruptly rise to >5× the upper limit of normal; this is thought to occur due to the immune response against an upsurge in serum HBV DNA and antigen levels. Hepatitis flares may occur spontaneously, during or after antiviral therapy, or upon immunosuppression or chemotherapy in both HBeAg-positive and HBeAg-negative patients. The clinical spectrum of HBV flares varies from asymptomatic to hepatic decompensation or failure. HBeAg seroconversion with ≥ 1 year of consolidation therapy is accepted as an endpoint of oral antiviral therapy in HBeAg-positive patients, but recommendations for treating HBeAg-negative patients differ. Thus, the management of HBeAg-negative patients has attracted increasing interest. In the current review, we summarize various types of HBV flares and the associated complex cascade of innate and adaptive immune responses, with a focus on HBeAg-negative CHB patients. Hopefully, this review will provide insight into immunopathogenesis to improve the management of HBV flares in HBeAg-negative CHB patients.
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Affiliation(s)
- Ming-Ling Chang
- College of Medicine, Chang Gung University, Taoyuan 333323, Taiwan;
- Division of Hepatology, Department of Hepatogastroenterology, Chang Gung Memorial Hospital, Taoyuan 333423, Taiwan
- Correspondence: ; Tel.: +886-3-3281200 (ext. 8107); Fax: +886-3-3272236
| | - Yun-Fan Liaw
- College of Medicine, Chang Gung University, Taoyuan 333323, Taiwan;
- Division of Hepatology, Department of Hepatogastroenterology, Chang Gung Memorial Hospital, Taoyuan 333423, Taiwan
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20
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Dokmak A, Trivedi HD, Bonder A, Wolf J. Pregnancy in Chronic Liver Disease: Before and After Transplantation. Ann Hepatol 2021; 26:100557. [PMID: 34656772 DOI: 10.1016/j.aohep.2021.100557] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/17/2021] [Revised: 05/27/2021] [Accepted: 05/27/2021] [Indexed: 02/04/2023]
Abstract
Chronic liver disease poses various challenges for women of reproductive age. Cirrhosis, particularly if decompensated, and liver transplantation may impact gestation and perinatal outcomes. Tailored management of underlying liver disease is critical to optimize maternal and fetal wellbeing. Early education, timely intervention, close monitoring, and a multidisciplinary approach are key elements required to minimize complications and increase chances of a safe and successful pregnancy. In this review, we focus on the pregnancy-related implications of chronic liver disease and liver transplantation on women of reproductive age and highlight disease-specific management considerations.
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Affiliation(s)
- Amr Dokmak
- Department of Hospital Medicine, Catholic Medical Center, Manchester, NH, USA.
| | - Hirsh D Trivedi
- Department of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
| | - Alan Bonder
- Liver Center, Department of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
| | - Jacqueline Wolf
- Department of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
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21
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Wang G, Duan Z. Guidelines for Prevention and Treatment of Chronic Hepatitis B. J Clin Transl Hepatol 2021; 9:769-791. [PMID: 34722192 PMCID: PMC8516840 DOI: 10.14218/jcth.2021.00209] [Citation(s) in RCA: 27] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/05/2021] [Revised: 07/20/2021] [Accepted: 08/03/2021] [Indexed: 12/12/2022] Open
Abstract
To achieve the goal of the World Health Organization to eliminate viral hepatitis as a major public health threat by 2030, the Chinese Society of Infectious Diseases and the Chinese Society of Hepatology convened an expert panel in 2019 to update the guidelines for the prevention and treatment of chronic hepatitis B (CHB). The current guidelines cover recent advances in basic, clinical, and preventive studies of CHB infection and consider the actual situation in China. These guidelines are intended to provide support for the prevention, diagnosis, and treatment of CHB.
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Affiliation(s)
- Guiqiang Wang
- Center for Liver Diseases, Department of Infectious Diseases, Peking University First Hospital; Department of Infectious and Liver Diseases, Peking University International Hospital, Beijing, China
| | - Zhongping Duan
- Center for Difficult and Complicated Liver Diseases and Artificial Liver, Beijing YouAn Hospital, Capital Medical University, Beijing, China
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22
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Veronese P, Dodi I, Esposito S, Indolfi G. Prevention of vertical transmission of hepatitis B virus infection. World J Gastroenterol 2021; 27:4182-4193. [PMID: 34326618 PMCID: PMC8311536 DOI: 10.3748/wjg.v27.i26.4182] [Citation(s) in RCA: 34] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/05/2021] [Revised: 03/29/2021] [Accepted: 06/02/2021] [Indexed: 02/06/2023] Open
Abstract
Hepatitis B virus (HBV) is the leading cause of chronic viral hepatitis. Annually, almost two million children younger than 5 years acquire the infection, mostly through vertical or horizontal transmission in early life. Vertical transmission of HBV is a high efficacy phenomenon ranging, in the absence of any preventive interventions, from 70% to 90% for hepatitis e antigen positive mothers and from 10% to 40% for hepatitis e antigen-negative mothers. Maternal viraemia is a preeminent risk factor for vertical transmission of HBV. Maternal screening is the first step to prevent vertical transmission of HBV. Hepatitis B passive and active immunoprophylaxis at birth together with antiviral treatment of highly viraemic mothers are the key strategies for global elimination of HBV infection. Strategies are needed to promote implementation of birth-dose vaccination and hepatitis B immunoglobulins in low- and middle-income countries where the prevalence of the infection is at the highest.
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Affiliation(s)
- Piero Veronese
- Department of Medicine and Surgery, University of Parma, Parma 43121, Italy
| | - Icilio Dodi
- Department of Pediatrics, Pietro Barilla Children's Hospital, Parma 43121, Italy
| | - Susanna Esposito
- Department of Medicine and Surgery, University of Parma, Parma 43121, Italy
| | - Giuseppe Indolfi
- Department Neurofarba, University of Florence, Florence 50129, Italy
- Department Neurofarba, Meyer Children's University Hospital, Florence 50129, Italy
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23
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Sirilert S, Tongsong T. Hepatitis B Virus Infection in Pregnancy: Immunological Response, Natural Course and Pregnancy Outcomes. J Clin Med 2021; 10:jcm10132926. [PMID: 34210105 PMCID: PMC8267880 DOI: 10.3390/jcm10132926] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2021] [Revised: 06/26/2021] [Accepted: 06/28/2021] [Indexed: 01/02/2023] Open
Abstract
This review aimed to provide an update on the impact of pregnancy on the natural course of hepatitis B virus (HBV) infection and also on the impact of HBV infection on adverse pregnancy outcomes, including mother-to-child transmission (MTCT). For the literature review, original research articles, review articles, and guidelines were narratively reviewed and comprehensively validated. The databases of PubMed, EMBASE, and CINAHL were carefully searched for articles in English on topics related to HBV infection, pregnancy, and vertical transmission from 1960 to May 2021. Immunological changes during pregnancy such as suppression of Th1 response and induction of Th2 immunity lead to an impaired immune reaction to HBV and stimulate viral activity along with the reduction of CD8 T cells to escape immune detection. The impact of pregnancy on the natural course of chronic HBV infection seems to be minimal, while pregnancy can increase morbidity and mortality in the case of advanced HBV hepatitis or cirrhosis. Importantly, hepatitis flare or alanine aminotransferase (ALT) flare can occur during pregnancy and is more common during the postpartum period due to the interaction between HBV and the immune response. Interestingly, the impact of HBV infection on adverse pregnancy outcomes is more serious than ever thought. Updated evidence indicates that pregnancies with chronic HBV infection increase the risk of preterm birth and gestational diabetes, especially in cases of positive hepatitis e antigen (HBeAg).
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24
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Abstract
Importance Vertical hepatitis B virus (HBV) transmission is the important route of chronic HBV infection. Although infant immunoprophylaxis is effective, a significant number of infants still become infected, most are associated with intrauterine infection. New evidences support intrauterine treatment in cases of high risk. Objective The aim of this study was to review the current evidences and recommendations for management of HBV infection in pregnancy. Evidence Acquisition Original research articles, review articles, and guidelines were reviewed. Results The management can be summarized as follows: (1) all pregnant women should be screened for hepatitis B surface antigen (HBsAg) and antibody to HBsAg. High-risk HBsAg-negative pregnant women without immunity should be vaccinated during pregnancy. (2) HBsAg-positive pregnant women should undergo further workup for liver status and indicative factors for immunoprophylaxis failure. (3) Pregnant women should be treated with HBV DNA levels greater than 200,000 IU/mL or 6 log copies/mL. (4) Antiviral drug should be started around 28 to 32 weeks. The first-line drug is tenofovir disoproxil fumarate. (5) Delivery route should be chosen based only on obstetric indications. (6) Breastfeeding is not contraindicated because it does not increase the risk of transmission in neonates with HBV vaccine and immunoglobulin administration. (7) Neonates born to HBsAg-positive mothers should receive HBV vaccine and immunoglobulin after birth as soon as possible. (8) Follow-up of the mothers and neonates is important. Beware of hepatitis flare after birth and after antiretroviral drug discontinuation; alanine transaminase assessment every 1 to 3 months until 6 months is suggested. Also, the schedule of infant vaccination and follow-up of serologic testing at 9 to 12 months old is needed.
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25
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Lee YS, Bang SM, Lee YS. Benefits and Risks of Antiviral Treatment during Pregnancy in Patients with Chronic Hepatitis B. J Clin Med 2021; 10:2320. [PMID: 34073357 PMCID: PMC8198811 DOI: 10.3390/jcm10112320] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2021] [Accepted: 05/25/2021] [Indexed: 12/12/2022] Open
Abstract
Hepatitis B virus (HBV) is a main cause of chronic liver disease worldwide and can lead to severe liver diseases. The World Health Organization has planned to eliminate viral hepatitis, including hepatitis caused by HBV and hepatitis C virus, by 2030. As mother-to-child transmission (MTCT) of HBV is a main cause of chronic HBV infection, MTCT prevention is the main target to reduce the risk of chronic HBV infection and eliminate the disease. Recent clinical trials and meta-analyses found that antiviral therapy could prevent MTCT effectively in mothers with ≥200,000 IU/mL of HBV DNA, in combination with serial vaccination and hepatitis B immune globulin administration in infants. Despite the preventive role of antivirals for MTCT of HBV, there are several concerns regarding antiviral therapy with respect to the safety of the mother and fetus during pregnancy. This review summarizes the benefits and risks of antiviral treatment during pregnancy in women with chronic HBV infection.
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Affiliation(s)
| | | | - Young-Sun Lee
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Korea University College of Medicine, Seoul 08308, Korea; (Y.S.L.); (S.M.B.)
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26
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Lu Y, Song Y, Zhai X, Zhu F, Liu J, Chang Z, Li Y, Xiao Y, Li L, Liu M, Liu J, Duan Z, Zou H, Zhuang H, Wang J, Li J. Maternal hepatitis B e antigen can be an indicator for antiviral prophylaxis of perinatal transmission of hepatitis B virus. Emerg Microbes Infect 2021; 10:555-564. [PMID: 33682609 PMCID: PMC8018376 DOI: 10.1080/22221751.2021.1899055] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/27/2022]
Abstract
As a high-risk factor of perinatal HBV transmission, the potential role of maternal hepatitis B e antigen (HBeAg) to guide antiviral prophylaxis has not yet been fully reported. This large prospective cohort study enrolled 1177 hepatitis B surface antigen (HBsAg)-positive pregnant women without antiviral treatment and their newborns. HBeAg, HBsAg, and viral load in maternal serum collected before delivery were measured. All the newborns were given standard passive-active immunoprophylaxis within 12 h after birth, and post-vaccination serologic testing was performed at 7 (±7d) months of age. The results revealed that 20 of the 1177 infants (1.70%) were immunoprophylaxis failure, and all their mothers were HBeAg positive. Maternal quantitative HBeAg was positively correlated with viral load (r = 0.83; P < .0001) and quantitative HBsAg (r = 0.68; P < .0001). The area under the receiver operating characteristic curve (AUC) for predicting immunoprophylaxis failure by maternal HBeAg was comparable to that by maternal viral load (0.871 vs 0.893; P = .441) and HBsAg (0.871 vs 0.871; P = .965). The optimal cutoff value of maternal quantitative HBeAg to predict perinatal infection was 2.21 log10 PEI U/mL, and the sensitivity and specificity was 100.0% and 74.5%, respectively. According to maternal viral load >2 × 105 IU/mL, the sensitivity and specificity of maternal qualitative HBeAg to identify the risk of HBV MTCT for pregnant women and determine the necessity for antiviral prophylaxis was 95.5% and 92.6%, respectively. This study showed that maternal HBeAg can be a surrogate marker of HBV DNA for monitoring and evaluating whether antiviral prophylaxis is necessary for preventing perinatal HBV transmission.
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Affiliation(s)
- Ying Lu
- Department of Microbiology & Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, People's Republic of China
| | - Yarong Song
- Department of Microbiology & Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, People's Republic of China
| | - Xiangjun Zhai
- Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, People's Republic of China
| | - Fengcai Zhu
- Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, People's Republic of China
| | - Jianxun Liu
- Zhengzhou Municipal Center for Disease Control and Prevention, Zhengzhou, People's Republic of China
| | - Zhanjun Chang
- Zhengzhou Municipal Center for Disease Control and Prevention, Zhengzhou, People's Republic of China
| | - Yi Li
- Department of Microbiology & Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, People's Republic of China
| | - Yiwei Xiao
- Department of Microbiology & Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, People's Republic of China
| | - Lili Li
- Department of Microbiology & Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, People's Republic of China
| | - Minmin Liu
- Department of Microbiology & Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, People's Republic of China
| | - Jia Liu
- Department of Microbiology & Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, People's Republic of China
| | - Zhongping Duan
- Beijing Youan Hospital, Capital Medical University, Beijing, People's Republic of China
| | - Huaibin Zou
- Beijing Youan Hospital, Capital Medical University, Beijing, People's Republic of China
| | - Hui Zhuang
- Department of Microbiology & Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, People's Republic of China
| | - Jie Wang
- Department of Microbiology & Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, People's Republic of China
| | - Jie Li
- Department of Microbiology & Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, People's Republic of China
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27
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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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28
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Terrault NA, Levy MT, Cheung KW, Jourdain G. Viral hepatitis and pregnancy. Nat Rev Gastroenterol Hepatol 2021; 18:117-130. [PMID: 33046891 DOI: 10.1038/s41575-020-00361-w] [Citation(s) in RCA: 65] [Impact Index Per Article: 16.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 08/21/2020] [Indexed: 02/06/2023]
Abstract
The management of viral hepatitis in the setting of pregnancy requires special consideration. There are five liver-specific viruses (hepatitis A, B, C, D, E), each with unique epidemiology, tendency to chronicity, risk of liver complications and response to antiviral therapies. In the setting of pregnancy, the liver health of the mother, the influence of pregnancy on the clinical course of the viral infection and the effect of the virus or liver disease on the developing infant must be considered. Although all hepatitis viruses can harm the mother and the child, the greatest risk to maternal health and subsequently the fetus is seen with acute hepatitis A virus or hepatitis E virus infection during pregnancy. By contrast, the primary risks for hepatitis B virus (HBV), hepatitis C virus (HCV) and hepatitis D virus are related to the severity of the underlying liver disease in the mother and the risk of mother-to-child transmission (MTCT) for HBV and HCV. The prevention of MTCT is key to reducing the global burden of chronic viral hepatitis, and prevention strategies must take into consideration local health-care and socioeconomic challenges. This Review presents the epidemiology of acute and chronic viral hepatitis infection in pregnancy, the effect of pregnancy on the course of viral infection and, conversely, the influence of the viral infection on maternal and infant outcomes, including MTCT.
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Affiliation(s)
- Norah A Terrault
- Keck School of Medicine, University of Southern California, Los Angeles, USA.
| | - Miriam T Levy
- Department of Gastroenterology and Liver, Liverpool Hospital, University of New South Wales, Sydney, New South Wales, Australia
| | - Ka Wang Cheung
- Department of Obstetrics and Gynaecology, Queen Mary Hospital, University of Hong Kong, Hong Kong, Hong Kong
| | - Gonzague Jourdain
- French National Research Institute for Sustainable Development (IRD), Marseille, France.,Chiang Mai University, Chiang Mai, Thailand
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29
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Sarkar M, Brady CW, Fleckenstein J, Forde KA, Khungar V, Molleston JP, Afshar Y, Terrault NA. Reproductive Health and Liver Disease: Practice Guidance by the American Association for the Study of Liver Diseases. Hepatology 2021; 73:318-365. [PMID: 32946672 DOI: 10.1002/hep.31559] [Citation(s) in RCA: 67] [Impact Index Per Article: 16.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/08/2020] [Accepted: 09/08/2020] [Indexed: 12/11/2022]
Affiliation(s)
- Monika Sarkar
- University of California, San Francisco, San Francisco, CA
| | | | | | | | | | - Jean P Molleston
- Indiana University and Riley Hospital for Children, Indianapolis, IN
| | - Yalda Afshar
- University of California, Los Angeles, Los Angeles, CA
| | - Norah A Terrault
- Keck School of Medicine, University of Southern California, Los Angeles, CA
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30
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Xiao LX, Chen YR, Huang P, Mei YY, Pan CQ, Lin CS. The safety of antiviral therapy and drug withdrawal for the prevention of mother-to-child transmission of HBV during pregnancy. J Med Virol 2020; 92:3381-3389. [PMID: 32410298 DOI: 10.1002/jmv.26011] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2020] [Revised: 05/02/2020] [Accepted: 05/07/2020] [Indexed: 12/17/2022]
Abstract
The efficacy of prenatal antiviral therapy (AVT) for preventing the vertical transmission of hepatitis B virus (HBV) is well demonstrated. However, data are limited regarding the safety of postpartum cessation of AVT, which may induce alanine aminotransferase (ALT) elevation. We aimed to investigate the necessity of prolonging maternal AVT after delivery. Chronic hepatitis B mothers at the immune-tolerant phase with HBV DNA levels >6 log10 IU/mL were prospectively enrolled and received AVT during the third trimester until delivery. Patients were offered to discontinue AVT either at delivery or postpartum week (PPW) 6. In addition, mothers who deferred AVT during pregnancy served as the control group. All mothers were followed until PPW 52 for clinical and virological parameters of hepatitis flares. Among 118 mothers recruited, 91 received AVT with 53 (group A) and 24 (group B) discontinue their treatment at delivery and PPW 6, respectively. Twenty-seven mothers who deferred AVT during pregnancy were followed as the control (group C). A total of 104 of 118 mothers who completed the study, 50% (52/104) had postpartum-elevated ALT levels, which were mild and moderate except 6 of 104 (5.77%) of patients had levels ≥5 times the upper limit of normal; 70% (36/52) of the ALT flares occurred within 12 weeks after delivery. In subgroup analyses, the frequency of ALT elevation was similar among the groups A vs B vs C (50.9% [27/53] vs 58.3% [14/24] vs 40.7% [11/27], respectively; P = .447), as well as the mean peak ALT level (108.4/74.1/126.7 U/L in groups A/B/C, respectively; P = .291). Although postpartum ALT flares were common for mothers with or without AVT during pregnancy, most cases of ALT elevation were mild to moderate. Our study observed that extending AVT to PPW 6 did not affect maternal outcomes and ATV should be discontinued at birth. Close monitoring is warranted as severe flares rarely occurred.
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Affiliation(s)
- Li-Xin Xiao
- Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China
| | - Yi-Ru Chen
- Department of Gastroenterology and Hepatology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Ping Huang
- Department of Infectious Diseases, The People's Hospital of Lianjiang, Lianjiang, Guangdong, China
| | - Yong-Yu Mei
- Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China
| | - Calvin Q Pan
- Department of Medicine, Center of Liver Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, China
- Division of Gastroenterology and Hepatology, Department of Medicine, NYU Langone Health, NYU School of Medicine, New York, New York
| | - Chao-Shuang Lin
- Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China
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31
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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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32
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Bierhoff M, Nelson KE, Guo N, Jia Y, Angkurawaranon C, Jittamala P, Carrara V, Watthanaworawit W, Ling C, Tongprasert F, van Vugt M, Rijken M, Nosten F, McGready R, Ehrhardt S, Thio CL. Prevention of mother-to-child transmission of hepatitis B virus: protocol for a one-arm, open-label intervention study to estimate the optimal timing of tenofovir in pregnancy. BMJ Open 2020; 10:e038123. [PMID: 32928858 PMCID: PMC7488796 DOI: 10.1136/bmjopen-2020-038123] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/28/2020] [Revised: 06/29/2020] [Accepted: 06/30/2020] [Indexed: 12/19/2022] Open
Abstract
INTRODUCTION Hepatitis B virus (HBV) remains a public health threat and the main route of transmission is from mother to child (MTCT). Tenofovir disoproxil fumarate (TDF) treatment can reduce MTCT of HBV although the optimal timing to attain undetectable HBV DNA concentrations at delivery is unknown. This protocol describes the procedures following early initiation of maternal TDF prior to 20 weeks gestation to determine efficacy, safety and feasibility of this approach in a limited-resource setting. METHODS AND ANALYSES One hundred and seventy pregnant women from the Thailand-Myanmar border between 12 and <20 weeks gestational age will be enrolled into a one-arm, open-label, TDF treatment study with cessation of TDF 1 month after delivery. Sampling occurs monthly prenatal, at birth and at 1, 2, 4 and 6 months post partum. Measurement of tenofovir concentrations in maternal and cord plasma is anticipated in 10-15 women who have detectable HBV DNA at delivery and matched to 20-30 women with no detectable HBV DNA. Infant HBsAg status will be determined at 2 months of age and HBV DNA confirmed in HBsAg positive cases. Adverse events including risk of flare and adherence, based on pill count and questionnaire, will be monitored. Infants will receive HBV vaccinations at birth, 2, 4 and 6 months and hepatitis B immunoglobulin at birth if the mother is hepatitis B e antigen positive. Infant growth and neurodevelopment at 6 months will be compared with established local norms. ETHICS AND DISSEMINATION This study has ethical approval by the Ethics Committee of the Faculty of Tropical Medicine, Mahidol University (FTM ECF-019-06), Johns Hopkins University (IRB no: 00007432), Chiang Mai University (FAM-2559-04227), Oxford Tropical Research Ethics Committee (OxTREC Reference: 49-16) and by the local Tak Community Advisory Board (TCAB-02/REV/2016). The article will be published as an open-access publication. TRIAL REGISTRATION NUMBER NCT02995005, Pre-results.
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Affiliation(s)
- Marieke Bierhoff
- Department of Maternal and Child health, Shoklo Malaria Research Unit, Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Mae Sot, Thailand
- Amsterdam UMC, Internal Medicine, Department of Infectious Diseases, Centre of Tropical Medicine and Travel Medicine, location AMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Kenrad E Nelson
- Department of Epidemiology, Johns Hopkins University, Baltimore, Maryland, USA
| | - Nan Guo
- Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University, Stanford, California, USA
| | - Yuanxi Jia
- Department of Epidemiology, Johns Hopkins University, Baltimore, Maryland, USA
| | | | - Podjanee Jittamala
- Department of Maternal and Child health, Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
- Department of Tropical Hygiene, Mahidol University Faculty of Medicine Ramathibodi Hospital, Bangkok, Thailand
| | - Verena Carrara
- Department of Maternal and Child health, Shoklo Malaria Research Unit, Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Mae Sot, Thailand
- Centre for Tropical Medicine and Global Health, Oxford University, Oxford, Oxfordshire, UK
| | - Wanitda Watthanaworawit
- Department of Microbiology, Shoklo Malaria Research Unit, Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Mae Sot, Thailand
| | - Clare Ling
- Centre for Tropical Medicine and Global Health, Oxford University, Oxford, Oxfordshire, UK
- Department of Microbiology, Shoklo Malaria Research Unit, Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Mae Sot, Thailand
| | - Fuanglada Tongprasert
- Department of Obstetrics and Gynecology, Chiang Mai University, Suthep, Chiang Mai, Thailand
| | - Michele van Vugt
- Amsterdam UMC, Internal Medicine, Department of Infectious Diseases, Centre of Tropical Medicine and Travel Medicine, location AMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Marcus Rijken
- Department of Obstetrics and Gynecology, Utrecht University, Utrecht, The Netherlands
| | - Francois Nosten
- Department of Maternal and Child health, Shoklo Malaria Research Unit, Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Mae Sot, Thailand
- Centre for Tropical Medicine and Global Health, Oxford University, Oxford, Oxfordshire, UK
| | - Rose McGready
- Department of Maternal and Child health, Shoklo Malaria Research Unit, Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Mae Sot, Thailand
- Centre for Tropical Medicine and Global Health, Oxford University, Oxford, Oxfordshire, UK
| | - Stephan Ehrhardt
- Department of Epidemiology, Johns Hopkins University, Baltimore, Maryland, USA
| | - Chloe Lynne Thio
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
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Bierhoff M, Rijken MJ, Yotyingaphiram W, Pimanpanarak M, van Vugt M, Angkurawaranon C, Nosten F, Ehrhardt S, Thio CL, McGready R. Tenofovir for prevention of mother to child transmission of hepatitis B in migrant women in a resource-limited setting on the Thailand-Myanmar border: a commentary on challenges of implementation. Int J Equity Health 2020; 19:156. [PMID: 32912268 PMCID: PMC7488314 DOI: 10.1186/s12939-020-01268-3] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2020] [Accepted: 08/25/2020] [Indexed: 12/16/2022] Open
Abstract
BACKGROUND The aim of this manuscript is to highlight challenges in the implementation of maternal tenofovir disoproxil fumarate (tenofovir) for prevention of mother to child transmission (PMTCT) of hepatitis B virus (HBV) in resource limited setting. Current preventive strategies in resource-limited settings fail mainly due to prohibitive costs of hepatitis B immunoglobulin (HBIG) and a high proportion of homebirths, meaning both HBIG and hepatitis B birth dose vaccine are not given. A new strategy for PMTCT without the necessity of HBIG, could be daily tenofovir commenced early in gestation. Implementation challenges to early tenofovir for PMTCT can provide insight to elimination strategies of HBV as the burden of disease is high in resource-limited settings. METHODS Challenges encountered during implementation of a study of tenofovir for PMTCT before 20 weeks gestation in rural and resource-limited areas on the Thailand-Myanmar border were identified informally from trial study logbooks and formally from comments from patients and staff at monthly visits. ClinicalTrials.gov Identifier: NCT02995005. MAIN BODY During implementation 171 pregnant women were hepatitis B surface antigen (HBsAg) positive by point of-care test over 19 months (May-2018 until Dec-2019). In this resource-limited setting where historically no clinic has provided tenofovir for PMTCT of HBV, information provided by staff resulted in a high uptake of study screening (95.5% (84/88) when offered to pregnant women. False positive point-of-care rapid tests hinder a test and treat policy for HBV and development of improved rapid tests that include HBeAg and/or HBV DNA would increase efficiency. Integrated care of HBV to antenatal care, transport assistance and local agreements to facilitate access, could increase healthcare at this critical stage of the life course. As safe storage of medication in households in resource-limited setting may not be ideal, interactive counseling about this must be a routine part of care. CONCLUSION Despite challenges, results from the study to date suggest tenofovir can be offered to HBV-infected women in resource-limited settings before 20 weeks gestation with a high uptake of screening, high drug accountability and follow-up, with provision of transportation support. This commentary has highlighted practical implementation issues with suggestions for strategies that support the objective of PMTCT and the World Health Organization goal of HBV elimination by 2030.
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Affiliation(s)
- M Bierhoff
- Shoklo Malaria Research Unit, Mahidol-Oxford Tropical Medicine Research Unit, Mahidol University, Mae Sot, 63110, Thailand.
- Division of Infectious Diseases, Academic UMC, University of Amsterdam, Amsterdam, The Netherlands.
| | - M J Rijken
- Department of Obstetrics and Gynaecology, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands
- Julius Global Health, The Julius Centre for Health Sciences, University Medical Centre Utrecht, Utrecht, Netherlands
| | - W Yotyingaphiram
- Shoklo Malaria Research Unit, Mahidol-Oxford Tropical Medicine Research Unit, Mahidol University, Mae Sot, 63110, Thailand
| | - M Pimanpanarak
- Shoklo Malaria Research Unit, Mahidol-Oxford Tropical Medicine Research Unit, Mahidol University, Mae Sot, 63110, Thailand
| | - M van Vugt
- Division of Infectious Diseases, Academic UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - C Angkurawaranon
- Department of Family Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand
| | - F Nosten
- Shoklo Malaria Research Unit, Mahidol-Oxford Tropical Medicine Research Unit, Mahidol University, Mae Sot, 63110, Thailand
- Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine Research Building, University of Oxford, Oxford, UK
| | - S Ehrhardt
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA
| | - C L Thio
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - R McGready
- Shoklo Malaria Research Unit, Mahidol-Oxford Tropical Medicine Research Unit, Mahidol University, Mae Sot, 63110, Thailand
- Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine Research Building, University of Oxford, Oxford, UK
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Evidence for Use of Tenofovir in Pregnancy to Prevent Perinatal Transmission of Hepatitis B Infection. Clin Obstet Gynecol 2020; 62:835-845. [PMID: 30921004 DOI: 10.1097/grf.0000000000000438] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
Perinatal transmission of hepatitis B virus continues to be a serious global public health concern. Transmission failures are related to high maternal viremia. Several antiviral therapies reduce maternal viremia around the time of delivery and decrease maternal-to-child-transmission. This chapter is a review of current studies that, ultimately, have provided strong evidence for the efficacy and safety of 3 antiviral drugs in pregnancy-lamivudine, telbivudine and tenofovir. The latter drug is the particular focus of this chapter which will show that tenofovir is the preferred antiviral therapy in pregnant women because of its potency, safety profile, and low risk of resistance.
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Efficacy and safety of antiviral prophylaxis during pregnancy to prevent mother-to-child transmission of hepatitis B virus: a systematic review and meta-analysis. THE LANCET. INFECTIOUS DISEASES 2020; 21:70-84. [PMID: 32805200 DOI: 10.1016/s1473-3099(20)30586-7] [Citation(s) in RCA: 116] [Impact Index Per Article: 23.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/11/2020] [Revised: 06/10/2020] [Accepted: 07/10/2020] [Indexed: 12/20/2022]
Abstract
BACKGROUND To eliminate mother-to-child transmission (MTCT) of hepatitis B virus (HBV), peripartum antiviral prophylaxis might be required for pregnant women infected with HBV who have a high risk of MTCT despite infant immunoprophylaxis. We aimed to determine the efficacy and safety of peripartum antiviral prophylaxis to inform the 2020 WHO guidelines. METHODS In this systematic review and meta-analysis, we searched PubMed, Embase, Scopus, CENTRAL, CNKI, and Wanfang for randomised controlled trials and non-randomised studies of peripartum antiviral prophylaxis versus placebo or no prophylaxis, with no language restriction, published from database inception until March 28, 2019. We used search terms covering HBV, antiviral therapy, and pregnancy. We included studies that enrolled pregnant women with chronic infection with HBV who received antiviral prophylaxis anytime during pregnancy; that included any of the following antivirals: adefovir, emtricitabine, entecavir, lamivudine, telbivudine, tenofovir alafenamide fumarate, and tenofovir disoproxil fumarate; and that reported the following outcomes: MTCT, indicated by infant HBsAg positivity or HBV DNA positivity, or both, at age 6-12 months, and any infant or maternal adverse events. Two reviewers independently extracted data. Our primary endpoint was MTCT based on infant HBsAg positivity. We assessed pooled odds ratios (ORs) of the efficacy of peripartum antiviral prophylaxis to reduce the risk of MTCT. We assessed safety of prophylaxis by pooling risk differences. The protocol for the systematic review was pre-registered in PROSPERO, CRD42019134614. FINDINGS Of 7463 articles identified, 595 articles were eligible for full-text review and 129 studies (in 157 articles) were included. The following antivirals were assessed in the meta-analysis: tenofovir disoproxil fumarate 300 mg (19 studies, with 1092 mothers and 1072 infants), lamivudine 100-150 mg (40 studies, with 2080 mothers and 2007 infants), and telbivudine 600 mg (83 studies, with 6036 mothers and 5971 infants). The pooled ORs for randomised controlled trials were similar, at 0·10 (95% CI 0·03-0·35) for tenofovir disoproxil fumarate, 0·16 (0·10-0·26) for lamivudine, and 0·14 (0·09-0·21) for telbivudine. The pooled ORs in non-randomised studies were 0·17 (0·10-0·29) for tenofovir disoproxil fumarate, 0·17 (0·12-0·24) for lamivudine, and 0·09 (0·06-0·12) for telbivudine. We found no increased risk of any infant or maternal safety outcomes after peripartum antiviral prophylaxis. INTERPRETATION Peripartum antiviral prophylaxis is highly effective at reducing the risk of HBV MTCT. Our findings support the 2020 WHO recommendation of administering antivirals during pregnancy, specifically tenofovir disoproxil fumarate, for the prevention of HBV MTCT. FUNDING World Health Organization.
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Gilleece DY, Tariq DS, Bamford DA, Bhagani DS, Byrne DL, Clarke DE, Clayden MP, Lyall DH, Metcalfe DR, Palfreeman DA, Rubinstein DL, Sonecha MS, Thorley DL, Tookey DP, Tosswill MJ, Utting MD, Welch DS, Wright MA. British HIV Association guidelines for the management of HIV in pregnancy and postpartum 2018. HIV Med 2020; 20 Suppl 3:s2-s85. [PMID: 30869192 DOI: 10.1111/hiv.12720] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Affiliation(s)
- Dr Yvonne Gilleece
- Honorary Clinical Senior Lecturer and Consultant Physician in HIV and Genitourinary Medicine, Brighton and Sussex University Hospitals NHS Trust
| | - Dr Shema Tariq
- Postdoctoral Clinical Research Fellow, University College London, and Honorary Consultant Physician in HIV, Central and North West London NHS Foundation Trust
| | - Dr Alasdair Bamford
- Consultant in Paediatric Infectious Diseases, Great Ormond Street Hospital for Children NHS Foundation Trust, London
| | - Dr Sanjay Bhagani
- Consultant Physician in Infectious Diseases, Royal Free Hospital NHS Trust, London
| | - Dr Laura Byrne
- Locum Consultant in HIV Medicine, St George's University Hospitals NHS Foundation Trust, London
| | - Dr Emily Clarke
- Consultant in Genitourinary Medicine, Royal Liverpool and Broadgreen University Hospitals NHS Trust
| | - Ms Polly Clayden
- UK Community Advisory Board representative/HIV treatment advocates network
| | - Dr Hermione Lyall
- Clinical Director for Children's Services and Consultant Paediatrician in Infectious Diseases, Imperial College Healthcare NHS Trust, London
| | | | - Dr Adrian Palfreeman
- Consultant in Genitourinary Medicine, University Hospitals of Leicester NHS Trust
| | - Dr Luciana Rubinstein
- Consultant in Genitourinary Medicine, London North West Healthcare University NHS Trust, London
| | - Ms Sonali Sonecha
- Lead Directorate Pharmacist HIV/GUM, Chelsea and Westminster Healthcare NHS Foundation Trust, London
| | | | - Dr Pat Tookey
- Honorary Senior Lecturer and Co-Investigator National Study of HIV in Pregnancy and Childhood, UCL Great Ormond Street Institute of Child Health, London
| | | | - Mr David Utting
- Consultant Obstetrician and Gynaecologist, Brighton and Sussex University Hospitals NHS Trust
| | - Dr Steven Welch
- Consultant in Paediatric Infectious Diseases, Heart of England NHS Foundation Trust, Birmingham
| | - Ms Alison Wright
- Consultant Obstetrician and Gynaecologist, Royal Free Hospitals NHS Foundation Trust, London
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Ghany MG, Feld JJ, Chang KM, Chan HLY, Lok ASF, Visvanathan K, Janssen HLA. Serum alanine aminotransferase flares in chronic hepatitis B infection: the good and the bad. Lancet Gastroenterol Hepatol 2020; 5:406-417. [PMID: 32057301 DOI: 10.1016/s2468-1253(19)30344-9] [Citation(s) in RCA: 73] [Impact Index Per Article: 14.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/14/2019] [Revised: 08/08/2019] [Accepted: 08/12/2019] [Indexed: 02/06/2023]
Abstract
Chronic hepatitis B virus (HBV) infection follows a dynamic and variable course. At different stages in the disease, hepatitis flares might occur, which can be challenging to predict and manage. Flares are believed to be primarily immune-mediated and might mark transitions to inactive disease or clearance of infection, but in certain scenarios they might also lead to hepatic decompensation or death. As such, understanding of the clinical significance of flares in different patient populations and different scenarios is important for optimal management. In this Review, we summarise what is known about flares in different stages of chronic HBV infection; describe flares in the context of the natural history of chronic infection; summarise the immunological mechanisms underlying flares, and describe flares in different clinical scenarios. Each section reviews existing knowledge and highlights key unanswered questions that need to be addressed to improve the understanding of flares, hopefully providing insights into their pathogenesis that can be used to improve current clinical management and ideally to further develop new curative therapeutic approaches for HBV infection. We also propose a working definition of an ALT flare to facilitate future research.
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Affiliation(s)
- Marc G Ghany
- Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA.
| | - Jordan J Feld
- Toronto Centre for Liver Disease, Toronto General Hospital, University of Toronto, Toronto, ON, Canada
| | - Kyong-Mi Chang
- Medical Research, Corporal Michael J Crescenz VA Medical Center, Philadelphia, PA, USA; Department of Medicine, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA
| | - Henry L Y Chan
- Department of Medicine and Therapeutics and Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China
| | - Anna S F Lok
- Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, MI, USA
| | - Kumar Visvanathan
- Department of Infectious Disease, St Vincent's Hospital, Melbourne, Victoria, Australia; Department of Medicine, The University of Melbourne, Melbourne, Victoria, Australia
| | - Harry L A Janssen
- Toronto Centre for Liver Disease, Toronto General Hospital, University of Toronto, Toronto, ON, Canada.
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Joshi SS, Coffin CS. Hepatitis B and Pregnancy: Virologic and Immunologic Characteristics. Hepatol Commun 2020; 4:157-171. [PMID: 32025602 PMCID: PMC6996345 DOI: 10.1002/hep4.1460] [Citation(s) in RCA: 29] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/31/2019] [Accepted: 11/23/2019] [Indexed: 12/18/2022] Open
Abstract
The hepatitis B virus (HBV) is an important human pathogen. Unvaccinated infants infected through mother-to-child transmission (MTCT) are at >95% risk of developing serum hepatitis B surface antigen-positive chronic hepatitis B (CHB). Despite complete passive-active HBV immunoprophylaxis, approximately 10% of infants born to mothers who are highly viremic develop CHB, and thus maternal treatment with nucleos(t)ide analogs (tenofovir disoproxil fumarate, lamivudine, or telbivudine) is recommended in the third trimester of pregnancy to reduce MTCT risk. Viral rebound usually occurs after stopping treatment and, in the context of maternal immunologic reconstitution postpartum, can also precipitate host immune-mediated hepatic (biochemical) flares. In this article, we review the epidemiology of HBV MTCT, discuss management and potential mechanisms of HBV vertical transmission, and highlight recent studies on virologic and immunologic aspects of hepatitis B in pregnancy and postpartum.
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Affiliation(s)
- Shivali S. Joshi
- Liver UnitDivision of Gastroenterology and HepatologyDepartment of MedicineUniversity of CalgaryCalgaryCanada
- Department of Microbiology, Immunology and Infectious DiseasesCumming School of MedicineUniversity of CalgaryCalgaryCanada
| | - Carla S. Coffin
- Liver UnitDivision of Gastroenterology and HepatologyDepartment of MedicineUniversity of CalgaryCalgaryCanada
- Department of Microbiology, Immunology and Infectious DiseasesCumming School of MedicineUniversity of CalgaryCalgaryCanada
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Lyu J, Wang S, He Q, Pan C, Tang AS. Hep B Moms: A cross-sectional study of mother-to-child transmission risk among pregnant Asian American women with chronic hepatitis B in New York City, 2007-2017. J Viral Hepat 2020; 27:168-175. [PMID: 31638292 DOI: 10.1111/jvh.13221] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/17/2019] [Revised: 10/01/2019] [Accepted: 10/05/2019] [Indexed: 01/01/2023]
Abstract
Mother-to-child transmission (MTCT) is responsible for the majority of chronic hepatitis B virus (HBV) infections worldwide. Despite timely HBV immunoprophylaxis of neonates, MTCT can occur in infants born to mothers with high levels of HBV viremia. We performed a retrospective cross-sectional analysis of Asian American women with chronic HBV evaluated with HBV DNA during prenatal care at two community health sites in New York City from 2007 to 2017. We described patient's demographic and clinical characteristics, categorized their HBV disease phase and analysed for variables associated with high MTCT risk (defined by HBV DNA level >200 000 IU/mL) using multivariable logistic regression. A total of 1298 pregnancies among 1012 mostly China-born (97.6%) women with chronic HBV were included in the study. Of the 1241 pregnancies among women not on antiviral treatment, 22.4% were considered high risk for MTCT and, of these, 255 (91.7%) were HBV e antigen (HBeAg)-positive and 19 (6.8%) were HBeAg-negative. HBeAg-positive status and ALT levels between 26 and 50 U/L were associated with higher likelihood for being high risk for MTCT. Only 0.8% of pregnancies low risk for MTCT were in the immune active phase while the majority (58.4%) were in the inactive chronic HBV phase of infection. Approximately one in five (22.4%) pregnancies among Asian American women with chronic HBV was considered high risk for MTCT and met criteria for antiviral therapy. Full assessment of HBV pregnant women and early coordinated care is needed to deliver interventions to prevent MTCT during critical windows of time.
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Affiliation(s)
- Janice Lyu
- Charles B. Wang Community Health Center, New York, NY, USA
| | - Su Wang
- Center for Asian Health, Saint Barnabas Medical Center, Florham Park, NJ, USA
| | - Qingqing He
- Charles B. Wang Community Health Center, New York, NY, USA
| | - Calvin Pan
- New York University Langone Health, New York, NY, USA
| | - Amy S Tang
- Charles B. Wang Community Health Center, New York, NY, USA
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Gao F, Zhang WT, Lin YY, Wang WM, Xu N, Bai GQ. Early Start Of Tenofovir Treatment Achieves Better Viral Suppression In Pregnant Women With A High HBV Viral Load: A Real-World Prospective Study. Infect Drug Resist 2019; 12:3475-3484. [PMID: 31807036 PMCID: PMC6844215 DOI: 10.2147/idr.s228982] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2019] [Accepted: 10/25/2019] [Indexed: 12/17/2022] Open
Abstract
PURPOSE To investigate whether tenofovir disoproxil fumarate (TDF) treatment that started from the second trimester had an advantage over TDF treatment that started from the third trimester. PATIENTS AND METHODS Twenty 35-year-old pregnant women with hepatitis B virus (HBV) DNA >2×106 IU/mL were prospectively enrolled in this study. All participants were divided into two subgroups: the second trimester group who started TDF treatment at 24-27 weeks and the third trimester group who started TDF treatment at 28-30 weeks. The primary outcome was the change in serum HBV DNA level from baseline to delivery. Each parameter was tested every 4 weeks from TDF initiation to 3 months postpartum. RESULTS There were 80 pregnant women in the second trimester group and 49 pregnant women in the third trimester group. The decline in HBV DNA from baseline to delivery was more obvious in the second trimester group (4.8±1.2 log10 IU/mL) than that in the third trimester group (4.3±1.1 log10 IU/mL, p=0.041). The downward shift of haemoglobin (HB) from baseline to delivery was greater in the second trimester group (10.6±10.7 g/L) than in the third trimester group (6.3±12.3 g/L, p=0.041). The decline in HBV DNA from baseline to delivery was linearly related to the start of TDF treatment from the second trimester (β=0.50 and 95% CI: 0.26-0.75, p<0.001). There were no significant differences between the two groups regarding HBV serologic markers and safety indicators. CONCLUSION Starting TDF treatment from the second trimester achieved better viral suppression than starting TDF treatment from the third trimester in highly viraemic pregnant women without increasing additional adverse reactions. HB level needed frequent monitoring during treatment to avoid anaemia. REGISTRY NUMBER Clinical Trial No. NCT02719808.
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Affiliation(s)
- Fan Gao
- Clinical Research Center, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi710061, People’s Republic of China
| | - Wen-Tao Zhang
- Department of Gynecology and Obstetrics, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi710061, People’s Republic of China
| | - Ya-Yun Lin
- Department of Gynecology and Obstetrics, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi710061, People’s Republic of China
| | - Wei-Min Wang
- Department of Gynecology and Obstetrics, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi710061, People’s Republic of China
| | - Na Xu
- Department of Gynecology and Obstetrics, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi710061, People’s Republic of China
| | - Gui-Qin Bai
- Department of Gynecology and Obstetrics, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi710061, People’s Republic of China
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Wang M, Hou Y, Meng SH, Yang B, Yang P, Zhang H, Zhu Y. Abnormal IL-10 levels were related to alanine aminotransferase abnormalities during postpartum in HBeAg positive women with chronic hepatitis B. Medicine (Baltimore) 2019; 98:e17969. [PMID: 31725660 PMCID: PMC6867749 DOI: 10.1097/md.0000000000017969] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/16/2023] Open
Abstract
Alanine transaminase (ALT) abnormalities are common in chronic hepatitis B (CHB) carriers during postpartum period. Disturbances in cytokines are considered to be associated with hepatitis Flares. There are limited data on cytokines changes in HBeAg positive patients with ALT abnormalities.This is an observational study. Pregnant patients with hepatitis B e-antigen (HBeAg) positive were enrolled from January 2014 to September 2018. Patients were assigned into three groups based on ALT levels in postpartum 6 to 8 weeks: ALT in normal range, ALT in 1 to 2-fold upper limits of normal (ULN) and ALT >2-fold ULN. Serum cytokines, ratios of regulatory T cells, and the concentration of cortisol were collected and compared among the three groups.Of the 135 mothers enrolled, 80.7% (109/135) completed the postpartum 6-week study. 13.8% (15/109) patients had postpartum ALT higher than 2ULN, 27.5% (30/109) patients had ALT in 1 to 2ULN and 58.7% (64/109) patients had ALT in normal range. Compared to control group, patients with ALT >2ULN had a higher IL-10 level (P < .05). No differences of IL-10 levels were found in the comparison of other inter comparison among three groups. No differences were found in the levels of other collected serum cytokines, cortisol, and regulatory T cells among three groups. On multivariate analysis, abnormal IL-10 level was independent risk factor for postpartum ALT elevating >2ULN. At the same time, the incidence of postpartum ALT elevated >2ULN were higher in patients with abnormal elevation IL-10 level than in patients with normal IL-10 level (14/68 vs 1/41, P = .008).CHB patients with postpartum ALT abnormalities show higher IL-10 level and postpartum ALT abnormalities were mainly occurred in patients with abnormal IL-10 level. IL-10 may be an underlying predictor and treatment target of hepatitis B, and further studies are needed.
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Affiliation(s)
- Ming Wang
- Department of Obstetrics and Gynecology, Beijing YouAn Hospital
- Department of Gynecologic Oncology, Beijing Obstetrics and Gynecology Hospital
| | - Ying Hou
- Department of Obstetrics and Gynecology, Beijing YouAn Hospital
| | - Shi-Hui Meng
- Department of Obstetrics and Gynecology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
| | - Bo Yang
- Department of Obstetrics and Gynecology, Beijing YouAn Hospital
| | - Ping Yang
- Department of Obstetrics and Gynecology, Beijing YouAn Hospital
| | - Hua Zhang
- Department of Obstetrics and Gynecology, Beijing YouAn Hospital
| | - Yunxia Zhu
- Department of Obstetrics and Gynecology, Beijing YouAn Hospital
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Liu J, Wang J, Qi C, Cao F, Tian Z, Guo D, Yan T, Li Q, Yang S, Fu J, Tang X, Kou X, Liu N, Jiang Z, Zhao Y, Chen T. Baseline Hepatitis B Virus Titer Predicts Initial Postpartum Hepatic Flare: A Multicenter Prospective Study. J Clin Gastroenterol 2019; 52:902-907. [PMID: 28654554 DOI: 10.1097/mcg.0000000000000877] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND AND GOALS A series of changes in the immune system occur during pregnancy and puerperium. Currently, we aim to characterize both the natural changes in liver inflammation and its association with hepatitis B viremia during this special period. PATIENTS AND METHODS Chronic hepatitis B (CHB) gravidas were recruited and followed up to 52 weeks postpartum. Virological and biochemical parameters were assessed throughout the period. RESULTS A total of 1097 CHB mothers had finished the entire follow-up including 451 accepting telbivudine, 178 accepting tenofovir, and 468 without antiviral therapy. Among the mothers, 11.94% went through hepatic flare in the first trimester and the rate decreased to 2.1% at the time of delivery. Nevertheless, a much higher frequency (19.78%) was observed in the early postpartum. Interestingly, alanine aminotransferase level decreased along with the development of pregnancy and then suddenly increased in the first month of puerperium. In addition, a downward trend was observed on the titer of HBsAg and HBeAg after delivery. Of note, an obvious higher frequency of alanine aminotransferase flare was revealed in mothers with high viremia (>6 log10 IU/mL). With multivariate analysis, only hepatitis B virus titer at baseline was strongly associated with hepatic flare during early postpartum (95% confidence interval, 1.012-3.049, P=0.045). The predictive rates of hepatic flare at baseline viral load of 6, 7, and 8 log10 IU/mL were 16.67%, 28.30%, and 30.60%, respectively. CONCLUSIONS CHB gravidas with high viremia should be monitored closely during entire pregnancy, and extended antiviral therapy is recommend to those mothers with baseline viremia >7 log10 IU/mL.
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Affiliation(s)
| | | | | | - Furong Cao
- Neonatology, the First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi Province, China
| | | | | | | | - Qian Li
- Departments of Infectious Disease
| | | | | | | | | | - Na Liu
- Departments of Infectious Disease
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Zhao M, Zou H, Chen Y, Duan Z. Mechanism and Antiviral Therapy in Preventing Mother-to-Child Transmission During Pregnancy with Hepatitis B Virus Infection. HEPATITIS MONTHLY 2019; 19. [DOI: 10.5812/hepatmon.81903] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 08/22/2024]
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Westin J, Aleman S, Castedal M, Duberg AS, Eilard A, Fischler B, Kampmann C, Lindahl K, Lindh M, Norkrans G, Stenmark S, Weiland O, Wejstål R. Management of hepatitis B virus infection, updated Swedish guidelines. Infect Dis (Lond) 2019; 52:1-22. [DOI: 10.1080/23744235.2019.1675903] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Affiliation(s)
- Johan Westin
- Deparment of Infectious Diseases, Institute of Biomedicine at the Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Soo Aleman
- Deparment of Medicine, Division of Infectious Diseases, Karolinska Institutet and Karolinska University Hospital Huddinge, Stockholm, Sweden
| | - Maria Castedal
- Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Ann-Sofi Duberg
- Deparment of Infectious Diseases, School of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro, Sweden
| | - Anders Eilard
- Deparment of Infectious Diseases, Institute of Biomedicine at the Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Björn Fischler
- Deparment of Pediatrics, CLINTEC, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden
| | - Christian Kampmann
- Deparment of Infectious Diseases, Skåne University Hospital Lund, Lund, Sweden
| | - Karin Lindahl
- Deparment of Medicine, Division of Infectious Diseases, Karolinska Institutet and Karolinska University Hospital Huddinge, Stockholm, Sweden
| | - Magnus Lindh
- Deparment of Infectious Diseases, Institute of Biomedicine at the Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Gunnar Norkrans
- Deparment of Infectious Diseases, Institute of Biomedicine at the Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Stephan Stenmark
- Deparment of Clinical Microbiology and Infectious Diseases, Umeå University, Umeå, Sweden
| | - Ola Weiland
- Deparment of Medicine, Division of Infectious Diseases, Karolinska Institutet and Karolinska University Hospital Huddinge, Stockholm, Sweden
| | - Rune Wejstål
- Deparment of Infectious Diseases, Institute of Biomedicine at the Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
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Sali S, Darvishi M, GhasemiAdl M, Akhlaghdoust M, Mirzazadeh A, Behjati SE, Sheikh-Zeinolabedini H, Shokouhi S, Tavakolpour S. Comparing the Efficacy and Safety of Treating Chronic Hepatitis B Infection during Pregnancy with Lamivudine, Telbivudine, and Tenofovir: A Meta-analysis. J Clin Transl Hepatol 2019; 7:197-212. [PMID: 31608211 PMCID: PMC6783676 DOI: 10.14218/jcth.2019.00021] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/07/2019] [Revised: 08/13/2019] [Accepted: 08/19/2019] [Indexed: 12/14/2022] Open
Abstract
Background and Aims: The perinatal transmission of hepatitis B virus (HBV) remains an important global health problem. Here, a systematic review and meta-analysis were conducted to evaluate the evidence regarding the efficacy and maternal/fetal safety of treating pregnant women with lamivudine, telbivudine (LdT), and tenofovir (TDF). Methods: A PubMed and Scopus search resulted in 1,076 records, which were reduced to 36, containing 7,717 pregnant women with chronic HBV infection and 7467 infants meeting the inclusion criteria. The latest search was in August 2019. Results: Treatment with LdT, but not lamivudine and TDF, could significantly reduce the hepatitis B virus surface antigen-positive rate (odds ratio (OR) = 0.37) in infants; it also led to higher rates of hepatitis B e antigen loss (OR = 12.14), hepatitis B e antigen seroconversion (OR = 8.93), and alanine aminotransferase normalization in mothers (OR = 1.49). Each of these treatments was able to significantly reduce HBV DNA positivity at birth (total OR = 0.19) and mother-to-child-transmission of HBV (total OR = 0.15), and to cause higher rates of HBV DNA suppression in mothers (total OR = 25.53). However, nucleos(t)ide analogues might also be involved in creatine kinase elevation (total OR = 7.48). In contrast, no significant association was found between nucleos(t)ide analogue therapy and preterm/premature births, congenital malformation, low birth weight, and abortion or fetal/infant death. The results suggested LdT's high capability of preventing mother-to-child-transmission. However, TDF failed to show significant associations to a reduced risk of mother-to-child-transmission, probably due to the low number of patients included. Conclusions: Although using either lamivudine, LdT, or TDF could lead to more favorable maternal/fetal outcomes, LdT seemed to show more potential in resolving certain infant- and maternal-related outcomes. More studies on the safety profile of such treatments are required.
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Affiliation(s)
- Shahnaz Sali
- Infectious Diseases and Tropical Medicine Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mohammad Darvishi
- Department of Aerospace and Subaquatic Medicine, Infectious Diseases and Tropical Medicine Research Center (IDTMRC), AJA University of Medical Sciences, Tehran, Iran
- Correspondence to: Soheil Tavakolpour, Infectious Diseases and Tropical Medicine Research Center, Shahid Beheshti University of Medical Sciences, Tehran 198396-3113, Iran. Tel/Fax: +98-2122267157, E-mail: ; Mohammad Darvishi, Department of Aerospace and Subaquatic Medicine, Infectious Diseases and Tropical Medicine Research Center (IDTMRC), AJA University of Medical Sciences, Tehran, Iran. E-mail:
| | - Mojtaba GhasemiAdl
- Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Meisam Akhlaghdoust
- Pars Advanced and Minimally Invasive Medical Manners Research Center, Pars Hospital, Iran University of Medical Sciences, Tehran, Iran
| | - Azin Mirzazadeh
- Joint Bioinformatics Graduate Program, University of Arkansas Little Rock and University of Arkansas for Medical Sciences, Little Rock, AR, USA
| | - Somayeh Elikaei Behjati
- The Genetics Department at Islamic Azad University, Science and Research Branch, Tehran, Iran
| | | | - Shervin Shokouhi
- Infectious Diseases and Tropical Medicine Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Soheil Tavakolpour
- Infectious Diseases and Tropical Medicine Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
- Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran
- Correspondence to: Soheil Tavakolpour, Infectious Diseases and Tropical Medicine Research Center, Shahid Beheshti University of Medical Sciences, Tehran 198396-3113, Iran. Tel/Fax: +98-2122267157, E-mail: ; Mohammad Darvishi, Department of Aerospace and Subaquatic Medicine, Infectious Diseases and Tropical Medicine Research Center (IDTMRC), AJA University of Medical Sciences, Tehran, Iran. E-mail:
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Hou J, Cui F, Ding Y, Dou X, Duan Z, Han G, Jia J, Mao Q, Li J, Li Z, Liu Z, Wei L, Xie Q, Yang X, Zhang H, Zhuang H. Management Algorithm for Interrupting Mother-to-Child Transmission of Hepatitis B Virus. Clin Gastroenterol Hepatol 2019; 17:1929-1936.e1. [PMID: 30312789 DOI: 10.1016/j.cgh.2018.10.007] [Citation(s) in RCA: 51] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/13/2018] [Revised: 09/29/2018] [Accepted: 10/02/2018] [Indexed: 02/07/2023]
Abstract
In areas where hepatitis B virus (HBV) is endemic, mother-to-child transmission (MTCT) is the major route of infection of children. Blocking MTCT of HBV therefore would reduce its prevalence. The China Foundation of Hepatitis Prevention and Control organized a team of specialists in infectious diseases, hepatology, immunology, obstetrics, and public health to develop an algorithm for interrupting MTCT of HBV, based on the most recent hepatitis B guidelines and latest evidence. This algorithm comprises 10 steps and has been adopted in clinical practice in China. Four aspects (screening, antiviral intervention during pregnancy, immunoprophylaxis, and postvaccination serologic testing) are the core components of preventing MTCT. Although the combination of passive and active immunization in newborns of hepatitis B surface antigen-positive mothers reduces MTCT of HBV, this immunoprophylaxis cannot completely eradicate MTCT. In the past decade, administration of antiviral agents to pregnant women has been shown to be safe and effective in reducing MTCT of HBV in combination with immunoprophylaxis. Aiming to achieve zero MTCT, this algorithm recommends the use of antivirals during pregnancy by women with high viral loads. Preventing MTCT is key to achieving the goal of eliminating HBV as a public health threat by 2030. Implementation and enhancement of the standardized algorithm for pregnant women with chronic HBV infection and their infants is urgently needed to prevent MTCT.
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Affiliation(s)
- Jinlin Hou
- Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China.
| | - Fuqiang Cui
- School of Public Health, Peking University, Beijing, China
| | - Yang Ding
- Department of Infectious Diseases, Shengjing Hospital, China Medical University, Shenyang, China
| | - Xiaoguang Dou
- Department of Infectious Diseases, Shengjing Hospital, China Medical University, Shenyang, China
| | - Zhongping Duan
- Artificial Liver Center, Beijing Youan Hospital, Capital Medical University, Beijing, China
| | - Guorong Han
- Department of Gynecology and Obstetrics, The Second Affiliated Hospital of the Southeast University, Nanjing, China
| | - Jidong Jia
- Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Qing Mao
- Department of Infectious Diseases, Southwest Hospital, Army Medical University, Chongqing, China
| | - Jie Li
- School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China
| | - Zengde Li
- China Foundation for Hepatitis Prevention and Control, Beijing, China
| | - Zhihua Liu
- Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Lai Wei
- Peking University Hepatology Institute, Peking University People's Hospital, Beijing, China
| | - Qing Xie
- Department of Infectious Diseases, Ruijin Hospital, Shanghai, China
| | - Xizhong Yang
- China Foundation for Hepatitis Prevention and Control, Beijing, China
| | - Hua Zhang
- Department of Gynecology and Obstetrics, Beijing Youan Hospital, Capital Medical University, Beijing, China
| | - Hui Zhuang
- School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China
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Total Alanine Aminotransferase (ALT) Flares in Pregnant North American Women With Chronic Hepatitis B Infection: Results From a Prospective Observational Study. Am J Gastroenterol 2019; 114:1283-1291. [PMID: 31082876 PMCID: PMC7132838 DOI: 10.14309/ajg.0000000000000221] [Citation(s) in RCA: 38] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
INTRODUCTION Alterations in the immune system can result in alanine aminotransferase (ALT) flares either during pregnancy or after delivery in women with chronic hepatitis B virus (HBV) infection. The aim of this study was to prospectively assess changes in serum biochemical and virological markers of HBV infection during and after pregnancy in a large North American cohort of pregnant women with chronic HBV. METHODS Adult pregnant women enrolled in the Hepatitis B Research Network between 2011 and 2016 were included. Serum ALT values and HBV DNA viral levels were obtained at <28 weeks and >28 weeks of gestation and <16 weeks, 16-31 weeks, and 32-48 weeks postpartum. Outcomes of ALT flares included severity, duration, and initiation of antiviral therapy. RESULTS Among the 158 pregnant women with chronic HBV, the median age was 33 years, 73% were Asian, and 63% were hepatitis B e antigen (HBeAg) negative. The median HBV DNA level was substantially higher in the HBeAg-positive vs HBeAg-negative women (1.3 × 10 vs 343 IU/mL), but serum ALT levels at their first study visit were similar. Among untreated pregnant women, there was a very mild increase in serum ALT postpartum among both HBeAg-positive and HBeAg-negative women (P < 0.001). Serum ALT flares (range 107-513 U/L) developed in 3.4% (5/149) during pregnancy and in 4.3% (4/92) after delivery. Twenty-two percent were initiated on antiviral therapy. After withdrawal of prophylactic anti-HBV therapy, 17.2% (5/29) developed serum ALT flares (range 107-208 U/L) within 14 weeks of drug discontinuation, and 3 additional women had flares despite continuous anti-HBV therapy during pregnancy or postpartum. Many ALT flares were not associated with significant changes in HBV DNA levels. No flares were severe with elevations of bilirubin or clinical decompensation. DISCUSSION Spontaneous ALT flares in untreated pregnant women with chronic HBV are infrequent, mild, and self-limited both prepartum and postpartum. Although flares after the withdrawal of antiviral therapy postpartum are more common, they were also mild and self-limited. Further studies of the immunopathogenesis of pregnancy-related flares are needed, as well as effects on long-term outcome of the mother and infant.
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Unnecessary to Extend Postpartum Antiviral Therapy in Pregnant Women With High Hepatitis B Viral Loads. J Clin Gastroenterol 2019; 53:473-474. [PMID: 30614940 DOI: 10.1097/mcg.0000000000001169] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
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Abstract
Liver diseases during pregnancy pose a unique clinical challenge because they can affect the lives of both the mother and unborn child. Although severe liver disease is rare, pregnancy-related liver disease affects approximately 3% of pregnancies and can be fatal. Timely recognition and diagnosis are essential in order to institute appropriate management strategies. This article provides an overview of liver diseases during pregnancy and is divided into 2 sections: (1) liver diseases specific to pregnancy, and (2) preexisting or coincident liver diseases during pregnancy.
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Affiliation(s)
- Karen Ma
- Section of Gastroenterology, Division of Digestive Diseases, Department of Internal Medicine, Rush University Medical Center, 1725 West Harrison Street, Suite 207, Chicago, IL 60612, USA
| | - Daniel Berger
- Section of Gastroenterology, Division of Digestive Diseases, Department of Internal Medicine, Rush University Medical Center, 1725 West Harrison Street, Suite 207, Chicago, IL 60612, USA
| | - Nancy Reau
- Section of Hepatology, Division of Digestive Diseases, Department of Internal Medicine, Rush University Medical Center, 1725 West Harrison Street, Suite 319, Chicago, IL 60612, USA.
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50
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Song J, Yang F, Wang S, Tikande S, Deng Y, Tang W, Cao G. Efficacy and safety of antiviral treatment on blocking the mother-to-child transmission of hepatitis B virus: A meta-analysis. J Viral Hepat 2019; 26:397-406. [PMID: 30417469 DOI: 10.1111/jvh.13036] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/24/2018] [Accepted: 10/25/2018] [Indexed: 02/06/2023]
Abstract
Nucleo(t)side analogues (NAs) have been administered as adjunctive therapy to interrupt the mother-to-child transmission (MTCT) of hepatitis B virus (HBV). The efficacy and safety of this method remain controversial. A meta-analysis was conducted to evaluate the efficacy and safety of NAs treatment during pregnancy. The differences among different agents and initiation trimesters were analysed. A total of 9228 mother-infant pairs in 59 studies (32 RCTs and 27 non-RCTs) were included in this meta-analysis. NAs significantly reduced the risk of MTCT, as indicated by seropositivity of hepatitis B surface antigen (HBsAg) (risk ratio (RR) = 0.51, 95% confidence interval (CI) 0.45-0.57) and HBV DNA in newborns (RR = 0.22, 95% CI 0.18-0.26). No differences in the efficacy of interrupting HBV MTCT were evident among lamivudine, telbivudine and tenofovir disoproxil fumarate. NA was more effective when administered from the second than from the third trimester as indicated by HBV DNA (RR: the second vs the third 0.08 vs 0.22, P = 0.010), but this effect was not evident as indicated by HBsAg (RR: the second vs the third 0.46 vs 0.53, P = 0.596). Antiviral treatment initiated from the second trimester did not confer a higher risk of safety problems in the newborns compared with treatment from the third trimester, as indicated by weight (P = 0.064), length (P = 0.491) and malformation rate (P = 0.635) of newborns. CONCLUSIONS: Lamivudine, telbivudine and tenofovir disoproxil fumarate are equally effective in blocking HBV MTCT. Antiviral treatment can be applied from the second trimester, without obvious safety concerns.
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Affiliation(s)
- Jiahui Song
- Department of Epidemiology, Second Military Medical University, Shanghai, China
| | - Fan Yang
- Department of Epidemiology, Second Military Medical University, Shanghai, China
| | - Shuo Wang
- Department of Epidemiology, Second Military Medical University, Shanghai, China
| | - Sakinatou Tikande
- Department of Epidemiology, Second Military Medical University, Shanghai, China
| | - Yang Deng
- Department of Epidemiology, Second Military Medical University, Shanghai, China
| | - Weina Tang
- Department of Epidemiology, Second Military Medical University, Shanghai, China
| | - Guangwen Cao
- Department of Epidemiology, Second Military Medical University, Shanghai, China
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