Research Progress on the Mechanism of Intrauterine Transmission of Hepatitis B Virus

doi:10.12280/gjszjk.20210435

Abstract

Abstract:

More than 50% of chronic hepatitis B virus (HBV) infections are transmitted from mother to child, and more than 90% of perinatal HBV infections develop into chronic carriers with a higher risk of cirrhosis and/or liver cancer. Intrauterine infection is the main cause of mother-to-child transmission of HBV due to the failure of combined immunization with hepatitis B vaccine and hepatitis B immunoglobulin. HBV intrauterine infection includes four ways: germ cell infection, transplacental barrier leakage, transplacental cell infection and peripheral blood mononuclear cell (PBMC). HBV can infect and cross all cellular layers of the placental barrier, especially the trophoblast layer. HBV traverses trophoblast cells through intracellular vesicle transport system. A variety of cytokines such as interleukin can regulate HBV infection of trophoblast cells. HBV induces the activation of PI3K/pAKT and Smad signaling pathways and EGFR/AKT signaling pathways of trophoblast cells, and then reduces apoptosis, thereby increasing the risk of HBV mother-to-child transmission. Pregnant women with HBV-DNA>2×10⁵ IU/L may take tenofovir orally after 24-28 weeks of pregnancy, so as to reduce the risk of HBV mother-to-child transmission.

Key words: Hepatitis B virus, Infectious disease transmission,vertical, Signal transduction, Cytokines, Antiviral therapy

YUAN Li-chao, QU Zu, BAI Xiao-xia. Research Progress on the Mechanism of Intrauterine Transmission of Hepatitis B Virus[J]. Journal of International Reproductive Health/Family Planning, 2022, 41(1): 57-61.

References 34

[1]	Hutin Y, Bulterys M. Prevention of Mother-to-Child Transmission of Hepatitis B Virus: Guidelines on Antiviral Prophylaxis in Pregnancy[M]. Geneva:World Health Organization, 2020:17-18.
[2]	Jing W, Liu J, Liu M. Eliminating mother-to-child transmission of HBV: progress and challenges in China[J]. Front Med, 2020, 14(1):21-29. doi: 10.1007/s11684-020-0744-2. doi: 10.1007/s11684-020-0744-2 URL
[3]	Xu DZ, Yan YP, Choi BC, et al. Risk factors and mechanism of transplacental transmission of hepatitis B virus: a case-control study[J]. J Med Virol, 2002, 67(1):20-26. doi: 10.1002/jmv.2187. doi: 10.1002/jmv.2187 pmid: 11920813
[4]	Bai X, Ran J, Zhao X, et al. The S100A10-AnxA2 complex is associated with the exocytosis of hepatitis B virus in intrauterine infection[J]. Lab Invest, 2022, 102(1):57-68. doi: 10.1038/s41374-021-00681-8. doi: 10.1038/s41374-021-00681-8 URL
[5]	Cui F, Shen L, Li L, et al. Prevention of Chronic Hepatitis B after 3 Decades of Escalating Vaccination Policy, China[J]. Emerg Infect Dis, 2017, 23(5):765-772. doi: 10.3201/eid2305.161477. doi: 10.3201/eid2305.161477 URL
[6]	Cooke GS, Andrieux-Meyer I, Applegate TL, et al. Accelerating the elimination of viral hepatitis: a Lancet Gastroenterology & Hepatology Commission[J]. Lancet Gastroenterol Hepatol, 2019, 4(2):135-184. doi: 10.1016/S2468-1253(18)30270-X. doi: 10.1016/S2468-1253(18)30270-X URL
[7]	Terrault NA, Lok A, McMahon BJ, et al. Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance[J]. Hepatology, 2018, 67(4):1560-1599. doi: 10.1002/hep.29800. doi: 10.1002/hep.29800 pmid: 29405329
[8]	Chandran JR, Raj SV. Efficacy of Antiviral Therapy in HBsAg-Positive Pregnant Women to Reduce Mother-to-Infant Transmission of Hepatitis B Virus[J]. J Obstet Gynaecol India, 2018, 68(5):355-359. doi: 10.1007/s13224-017-1044-x. doi: 10.1007/s13224-017-1044-x URL
[9]	Wang DD, Yi LZ, Wu LN, et al. Relationship between Maternal PBMC HBV cccDNA and HBV Serological Markers and its Effect on HBV Intrauterine Transmission[J]. Biomed Environ Sci, 2019, 32(5):315-323. doi: 10.3967/bes2019.043. doi: 10.3967/bes2019.043 pmid: 31217048
[10]	Peng S, Wan Z, Liu T, et al. Incidence and Risk Factors of Intrauterine Transmission Among Pregnant Women With Chronic Hepatitis B Virus Infection[J]. J Clin Gastroenterol, 2019, 53(1):51-57. doi: 10.1097/MCG.0000000000001001. doi: 10.1097/MCG.0000000000001001 URL
[11]	Eke AC, Eleje GU, Eke UA, et al. Hepatitis B immunoglobulin during pregnancy for prevention of mother-to-child transmission of hepatitis B virus[J]. Cochrane Database Syst Rev, 2017, 2(2):CD008545. doi: 10.1002/14651858.CD008545.pub2. doi: 10.1002/14651858.CD008545.pub2
[12]	Ignatova EN, Tupoleva TA, Ovchinnikova EN, et al. Impact of current approaches to laboratory screening of donated blood and its components on hepatitis B virus infection in patients with blood system diseases[J]. Ter Arkh, 2017, 89(11):27-34. doi: 10.17116/terarkh2017891127-34. doi: 10.17116/terarkh2017891127-34
[13]	Cheung KW, Lao TT. Hepatitis B - Vertical transmission and the prevention of mother-to-child transmission[J]. Best Pract Res Clin Obstet Gynaecol, 2020, 68:78-88. doi: 10.1016/j.bpobgyn.2020. 02.014. doi: 10.1016/j.bpobgyn.2020. 02.014 URL
[14]	Jin L, Nie R, Li Y, et al. Hepatitis B surface antigen in oocytes and embryos may not result in vertical transmission to offspring of hepatitis B virus carriers[J]. Fertil Steril, 2016, 105(4):1010-1013. doi: 10.1016/j.fertnstert.2015.12.008. doi: 10.1016/j.fertnstert.2015.12.008 URL
[15]	Karamolahi S, Yazdi RS, Zangeneh M, et al. Impact of hepatitis B virus and hepatitis C virus infection on sperm parameters of infertile men[J]. Int J Reprod Biomed, 2019, 17(8):551-556. doi: 10.18502/ijrm.v17i8.4820. doi: 10.18502/ijrm.v17i8.4820 pmid: 31583372
[16]	León-Juárez M, Martínez-Castillo M, González-García LD, et al. Cellular and molecular mechanisms of viral infection in the human placenta[J]. Pathog Dis, 2017, 75(7):ftx093. doi: 10.1093/femspd/ftx093. doi: 10.1093/femspd/ftx093
[17]	Liu L, Liu X. Contributions of Drug Transporters to Blood-Placental Barrier[J]. Adv Exp Med Biol, 2019, 1141:505-548. doi: 10.1007/978-981-13-7647-4_11. doi: 10.1007/978-981-13-7647-4_11 pmid: 31571173
[18]	Narang K, Cheek EH, Enninga E, et al. Placental Immune Responses to Viruses: Molecular and Histo-Pathologic Perspectives[J]. Int J Mol Sci, 2021, 22(6):2921. doi: 10.3390/ijms22062921. doi: 10.3390/ijms22062921 URL
[19]	Huang H, Ning M, Liu J, et al. Comparison of antibody response to hepatitis B vaccination in infants with positive or negative maternal hepatitis B e antigen (HBeAg) in cord blood: implication for the role of HBeAg as an immunotolerogen[J]. Hum Vaccin Immunother, 2019, 15(9):2183-2186. doi: 10.1080/21645515.2019.1575712. doi: 10.1080/21645515.2019.1575712 URL
[20]	Huang JT, Yang Y, Hu YM, et al. A Highly Sensitive and Robust Method for Hepatitis B Virus Covalently Closed Circular DNA Detection in Single Cells and Serum[J]. J Mol Diagn, 2018, 20(3):334-343. doi: 10.1016/j.jmoldx.2018.01.010. doi: 10.1016/j.jmoldx.2018.01.010 URL
[21]	Xu YY, Liu HH, Zhong YW, et al. Peripheral blood mononuclear cell traffic plays a crucial role in mother-to-infant transmission of hepatitis B virus[J]. Int J Biol Sci, 2015, 11(3):266-273. doi: 10.7150/ijbs.10813. doi: 10.7150/ijbs.10813 URL
[22]	Joshi SS, Coffin CS. Hepatitis B and Pregnancy: Virologic and Immunologic Characteristics[J]. Hepatol Commun, 2020, 4(2):157-171. doi: 10.1002/hep4.1460. doi: 10.1002/hep4.1460 URL
[23]	Sirilert S, Khamrin P, Kumthip K, et al. Placental infection of hepatitis B virus among Thai pregnant women: Clinical risk factors and its association with fetal infection[J]. Prenat Diagn, 2020, 40(3):380-386. doi: 10.1002/pd.5628. doi: 10.1002/pd.5628 URL
[24]	Das UN. Beneficial role of bioactive lipids in the pathobiology, prevention, and management of HBV, HCV and alcoholic hepatitis, NAFLD, and liver cirrhosis: A review[J]. J Adv Res, 2019, 17:17-29. doi: 10.1016/j.jare.2018.12.006. doi: 10.1016/j.jare.2018.12.006 URL
[25]	Li F, Wang X, Men K, et al. Receptivity of human choriocarcinoma JEGIII cells and isolated trophoblast cells to hepatitis B virus infection and enhancement by tumor necrosis factor alpha[J]. Jpn J Infect Dis, 2007, 60(4):167-172.
[26]	Cui H, Chen J, Na Q. Effect of hepatitis B virus infection on trophoblast cell line (HTR-8/SVneo) and choriocarcinoma cell line (JEG3) is linked to CD133-2 (AC141) expression[J]. Am J Transl Res, 2016, 8(7):3235-3240.
[27]	Cui H, Li QL, Chen J, et al. Hepatitis B virus X protein modifies invasion, proliferation and the inflammatory response in an HTR-8/SVneo cell model[J]. Oncol Rep, 2015, 34(4):2090-2098. doi: 10.3892/or.2015.4172. doi: 10.3892/or.2015.4172 URL
[28]	Bai G, Wang Y, Zhang L, et al. The study on the role of hepatitis B virus X protein and apoptosis in HBV intrauterine infection[J]. Arch Gynecol Obstet, 2012, 285(4):943-949. doi: 10.1007/s00404-011-2096-2. doi: 10.1007/s00404-011-2096-2 URL
[29]	Wang W, Bai G, Zhang Y, et al. HBxAg suppresses cell apoptosis and promotes the secretion of placental hormones in human placental trophoblasts via activation of the EGFR/Akt pathway[J]. Cell Biol Int, 2018, 42(2):237-247. doi: 10.1002/cbin.10891. doi: 10.1002/cbin.10891 URL
[30]	Chen HL, Zha ML, Cai JY, et al. Maternal viral load and hepatitis B virus mother-to-child transmission risk: A systematic review and meta-analysis[J]. Hepatol Res, 2018, 48(10):788-801. doi: 10.1111/hepr.13072. doi: 10.1111/hepr.13072 URL
[31]	中华医学会感染病学分会. 阻断乙型肝炎病毒母婴传播临床管理流程(2021 年)[J]. 临床肝胆病杂志, 2021, 37(3):527-531. doi: 10.3969/j.issn.1001-5256.2021.03.007. doi: 10.3969/j.issn.1001-5256.2021.03.007
[32]	徐陈瑜, 陈廷美. 对《中国乙型肝炎病毒母婴传播防治指南(2019年版)》的若干探讨意见[J]. 肝脏, 2020, 25(3):228-230. doi: 10.3969/j.issn.1008-1704.2020.03.003. doi: 10.3969/j.issn.1008-1704.2020.03.003
[33]	Wu Y, Liu J, Feng Y, et al. Efficacy and safety of antiviral therapy for HBV in different trimesters of pregnancy: systematic review and network meta-analysis[J]. Hepatol Int, 2020, 14(2):180-189. doi: 10.1007/s12072-020-10026-0. doi: 10.1007/s12072-020-10026-0 URL
[34]	Jourdain G, Ngo-Giang-Huong N,, Harrison L, et al. Tenofovir versus Placebo to Prevent Perinatal Transmission of Hepatitis B[J]. N Engl J Med, 2018, 378(10):911-923. doi: 10.1056/NEJMoa1708131. doi: 10.1056/NEJMoa1708131 URL