Eliminating mother-to-child transmission of HBV: progress and challenges in China

Abstract

China has the world’s largest burden of hepatitis B virus (HBV) infection, but the country has made considerable progress in preventing its mother-to-child transmission (MTCT) in the past three decades. This feat is made possible due to the high coverage of birth-dose hepatitis B vaccine (HepB,>95%), hepatitis B surface antigen (HBsAg) screening for pregnant women (>99%), and hepatitis B immunoglobulin plus HepB for newborns whose mothers are HBsAg positive (>99%). Studies on the optimal antiviral treatment regimen for pregnant women with high HBV-DNA load have also been conducted. However, China still faces challenges in eliminating MTCT of HBV. The overall HBsAg prevalence among pregnant women is considered an intermediate endemic. The prevalence of HBsAg among pregnant women from remote, rural, or ethnic minority areas is higher than that of the national level because of limited health resources and public health education for HBV. The coverage for maternal and child healthcare and immunization services should be improved, especially in western regions. Integration of current services to prevent MTCT of HBV with other relevant health services can increase the acceptability, efficiency, and coverage of these services, particularly in remote areas and ethnic minority areas. By doing so, progress toward key milestones and targets to eliminate hepatitis B as the main public health threat by 2030 can be achieved.

Keywords

hepatitis B virus / mother-to-child transmission / progress / challenge

References

[1] Cheung KW, Seto MTY, Lao TTH. Prevention of perinatal hepatitis B virus transmission. Arch Gynecol Obstet 2019; 300(2): 251–259

[2] Chinese Medical Association Obstetrics and Gynecology Branch. Clinical guidelines for prevention of mother-to-child transmission of hepatitis B virus (1st Edition). Chin J Obstet Gynecol (Zhonghua Fu Chan Ke Za Zhi) 2013; (2): 151–154 (in Chinese)

[3] World Health Organization. Guidelines for the prevention, care and treatment of persons with chronic hepatitis B infection. Geneva, Switzerland: World Health Organization, 2015. http://apps.who.int/iris/bitstream/handle/10665/154590/9789241549059_eng.pdf;jsessionid=C45FBB6C849F7F96F2213274A3FE2336?sequence=1 (accessed May 15, 2018)

[4] World Health Organization. Global hepatitis report, 2017. Geneva, Switzerland: World Health Organization, 2017. http://www.who.int/hepatitis/publications/global-hepatitis-report2017/en/# (accessed January 12, 2018)

[5] Liaw YF, Chu CM. Hepatitis B virus infection. Lancet 2009; 373(9663): 582–592

[6] Wang FS, Fan JG, Zhang Z, Gao B, Wang HY. The global burden of liver disease: the major impact of China. Hepatology 2014; 60(6): 2099–2108

[7] Yin RX, Liu ZH, Liu ZH, Li J, Zhuang H, Dou XG, Hou JL. Getting to zero mother-to-child transmission of hepatitis B virus: dream and challenge. Chin J Hepatol (Zhonghua Gan Zang Bing Za Zhi) 2018; (4): 262–265 (in Chinese)

[8] Trépo C, Chan HL, Lok A. Hepatitis B virus infection. Lancet 2014; 384(9959): 2053–2063

[9] Polaris Observatory Collaborators. Global prevalence, treatment, and prevention of hepatitis B virus infection in 2016: a modelling study. Lancet Gastroenterol Hepatol 2018; 3(6): 383–403

[10] World Health Organization. Tenofovir reduces mother-to-child transmission of hepatitis B: new study. Geneva, Switzerland: World Health Organization, 2016. https://www.who.int/hepatitis/news-events/hbv-mtct-tenofovir/en/ (accessed January 15, 2019)

[11] Xu Y, Liu H, Wang Y, Hao R, Li Z, Song H. The next step in controlling HBV in China. BMJ 2013; 347: f4503

[12] Liang X, Bi S, Yang W, Wang L, Cui G, Cui F, Zhang Y, Liu J, Gong X, Chen Y, Wang F, Zheng H, Wang F, Guo J, Jia Z, Ma J, Wang H, Luo H, Li L, Jin S, Hadler SC, Wang Y. Epidemiological serosurvey of hepatitis B in China—declining HBV prevalence due to hepatitis B vaccination. Vaccine 2009; 27(47): 6550–6557

[13] Liu J, Liang W, Jing W, Liu M. Countdown to 2030: eliminating hepatitis B disease, China. Bull World Health Organ 2019; 97(3): 230–238

[14] Global Burden of Disease Collaborative Network. Global Burden of Disease Study 2017 (GBD 2017) Results. Seattle, United States: Institute for Health Metrics and Evaluation (IHME). 2018. http://ghdx.healthdata.org/gbd-results-tool (accessed April 20, 2018)

[15] World Health Organization. Global health sector strategy on viral hepatitis 2016–2021. Geneva, Switzerland: World Health Organization, 2016. http://www.who.int/hepatitis/strategy2016-2021/ghss-hep/en/ (accessed March 29, 2018)

[16] World Health Organization. Regional Office for the Western Pacific. Regional framework for the triple elimination of mother-to-child transmission of HIV, hepatitis B and syphilis in Asia and the Pacific, 2018–2030. Geneva, Switzerland: World Health Organization, 2018. http://iris.wpro.who.int/handle/10665.1/14193 (accessed April 10, 2018)

[17] Cui F, Liang X, Gong X, Chen Y, Wang F, Zheng H, Wu Z, Miao N, Hadler SC, Hutin YJ, Luo H, Yang W. Preventing hepatitis B though universal vaccination: reduction of inequalities through the GAVI China project. Vaccine 2013; 31(Suppl 9): J29–J35

[18] Cui F, Luo H, Wang F, Zheng H, Gong X, Chen Y, Wu Z, Miao N, Kane M, Hennessey K, Hadler SC, Hutin YJ, Liang X, Yang W. Evaluation of policies and practices to prevent mother to child transmission of hepatitis B virus in China: results from China GAVI project final evaluation. Vaccine 2013; 31(Suppl 9): J36–J42

[19] National Health Commission of the People’s Republic of China. The National Health Commission held a press conference on July 25, 2017 (in Chinese) http://www.nhc.gov.cn/xcs/s3574/201707/10ae796284de4d40a58b36502e145961.shtml (accessed April 10, 2019)

[20] National Health Commission of the People’s Republic of China. The 2018 China Health Statistics Yearbook. Beijing: China Union Medical University Press, 2018 (in Chinese)

[21] Liang X, Bi S, Yang W, Wang L, Cui G, Cui F, Zhang Y, Liu J, Gong X, Chen Y, Wang F, Zheng H, Wang F, Guo J, Jia Z, Ma J, Wang H, Luo H, Li L, Jin S, Hadler SC, Wang Y. Evaluation of the impact of hepatitis B vaccination among children born during 1992–2005 in China. J Infect Dis 2009; 200(1): 39–47

[22] Cui J, Cao L, Zheng J, Cao L, Duo M, Xiao Q. Reported coverage of vaccines in the National Immunization Program of China, 2015. Chin J vacc and imm (Zhongguo Yi Miao He Mian Yi) 2017; (6): 601–607 (in Chinese)

[23] Cui F, Shen L, Li L, Wang H, Wang F, Bi S, Liu J, Zhang G, Wang F, Zheng H, Sun X, Miao N, Yin Z, Feng Z, Liang X, Wang Y. Prevention of chronic hepatitis B after 3 decades of escalating vaccination policy, China. Emerg Infect Dis 2017; 23(5): 765–772

[24] Xia GL, Liu CB, Cao HL, Bi SL, Zhan MY, Su CA, Nan JH, Qi XQ. Prevalence of hepatitis B and C virus infections in the general Chinese population. Results from a nationwide cross-sectional seroepidemiologic study of hepatitis A, B, C, D, and E virus infections in China, 1992. Int Hepatol Commun 1996; 5(1): 62–73

[25] Thio CL, Guo N, Xie C, Nelson KE, Ehrhardt S. Global elimination of mother-to-child transmission of hepatitis B: revisiting the current strategy. Lancet Infect Dis 2015; 15(8): 981–985

[26] National Health Commission of the People’s Republic of China. Comprehensive Prevention of Mother-to-Child Transmission for HIV, Syphilis and Hepatitis B. April, 2015 (in Chinese) http://www.nhfpc.gov.cn/fys/s3581/201506/4f2123fa955a44afa75a75da2ad35d6e.shtml (accessed April 22, 2018)

[27] Wang AL, Qiao YP, Wang LH, Fang LW, Wang F, Jin X, Qiu J, Wang XY, Wang Q, Wu JL, Vermund SH, Song L. Integrated prevention of mother-to-child transmission for human immunodeficiency virus, syphilis and hepatitis B virus in China. Bull World Health Organ 2015; 93(1): 52–56

[28] National Health Commission of the People’s Republic of China. Prevention of Mother-to-Child Tansmission for Human Immunodeficiency Virus, Syphilis and Hepatitis B Virus Work Plan. 2011 (in Chinese) http://www.nhfpc.gov.cn/fys/s3581/201102/a0c03b2192a1483384b4f798d9ba603d.shtml (accessed March 28, 2018)

[29] Wang A, Qiao Y, Dou L, Wang Q, Wang X, Su M, Li Z, Huang X, Yang Y, Jin X, Song L. Challenges of eliminating mother-to-child transmission of HIV, syphilis and hepatitis B in China: a cross-sectional survey. Lancet 2018; 392(Supplement 1): S55

[30] Yuhang Government, Zhejiang Province, China. Yuhang Becomes a National Pilot Area to Eliminate of Mother-to-Child Transmission for HIV, syphilis and hepatitis B virus Project. September 2017 (in Chinese) http://www.yuhang.gov.cn/zjyh/jryh/news/201709/t20170914_1100547.html (accessed April 29, 2018)

[31] Lin X, Guo Y, Zhou A, Zhang Y, Cao J, Yang M, Xiao F, Zhang B, Du Y. Immunoprophylaxis failure against vertical transmission of hepatitis B virus in the Chinese population: a hospital-based study and a meta-analysis. Pediatr Infect Dis J 2014; 33(9): 897–903

[32] Zou H, Chen Y, Duan Z, Zhang H, Pan C. Virologic factors associated with failure to passive-active immunoprophylaxis in infants born to HBsAg-positive mothers. J Viral Hepat 2012; 19(2): e18–e25

[33] Wiseman E, Fraser MA, Holden S, Glass A, Kidson BL, Heron LG, Maley MW, Ayres A, Locarnini SA, Levy MT. Perinatal transmission of hepatitis B virus: an Australian experience. Med J Aust 2009; 190(9): 489–492

[34] Peng S, Wan Z, Liu T, Zhu H, Du Y. Incidence and risk factors of intrauterine transmission among pregnant women with chronic hepatitis B virus infection. J Clin Gastroenterol 2019; 53(1): 51–57

[35] Jourdain G, Ngo-Giang-Huong N, Harrison L, Decker L, Khamduang W, Tierney C, Salvadori N, Cressey TR, Sirirungsi W, Achalapong J, Yuthavisuthi P, Kanjanavikai P, Na Ayudhaya OP, Siriwachirachai T, Prommas S, Sabsanong P, Limtrakul A, Varadisai S, Putiyanun C, Suriyachai P, Liampongsabuddhi P, Sangsawang S, Matanasarawut W, Buranabanjasatean S, Puernngooluerm P, Bowonwatanuwong C, Puthanakit T, Klinbuayaem V, Thongsawat S, Thanprasertsuk S, Siberry GK, Watts DH, Chakhtoura N, Murphy TV, Nelson NP, Chung RT, Pol S, Chotivanich N. Tenofovir versus placebo to prevent perinatal transmission of hepatitis B. N Engl J Med 2018; 378(10): 911–923

[36] Wei KP, Zhu FC, Liu JX, Yan L, Lu Y, Zhai XJ, Chang ZJ, Zeng Y, Li J, Zhuang H. The efficacy of two different dosages of hepatitis B immunoglobulin combined with hepatitis B vaccine in preventing mother-to-child transmission of hepatitis B virus: a prospective cohort study. Vaccine 2018; 36(2): 256–263

[37] 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(10): 1929–1936.e1

[38] Zheng H, Zhang GM, Chan PL, Wang FZ, Rodewald LE, Miao N, Sun XJ, Yin ZD, Edwards J, Wang HQ. Compliance among infants exposed to hepatitis B virus in a post-vaccination serological testing program in four provinces in China. Infect Dis Poverty 2019; 8(1): 57

[39] Fan R, Yin X, Liu Z, Liu Z, Lau G, Hou J. A hepatitis B-free generation in China: from dream to reality. Lancet Infect Dis 2016; 16(10): 1103–1105

[40] Pan CQ, Duan Z, Dai E, Zhang S, Han G, Wang Y, Zhang H, Zou H, Zhu B, Zhao W, Jiang H; China Study Group for the Mother-to-Child Transmission of Hepatitis B. Tenofovir to prevent hepatitis B transmission in mothers with high viral load. N Engl J Med 2016; 374(24): 2324–2334

[41] Sheng Q, Ding Y, Li B, Han C, Li Y, Zhang C, Bai H, Wang J, Zhao L, Xia T, An Z, Zhang M, Dou X. Efficacy and safety of nucleos(t)ide analogues to prevent hepatitis B virus mother-to-child transmission in pregnant women with high viremia: real life practice from China. Int J Med Sci 2018; 15(8): 796–801

[42] Wang M, Bian Q, Zhu Y, Pang Q, Chang L, Li R, Tiongson BC, Zhang H, Pan CQ. Real-world study of tenofovir disoproxil fumarate to prevent hepatitis B transmission in mothers with high viral load. Aliment Pharmacol Ther 2019; 49(2): 211–217

[43] Hou J, Wang G, Wang F, Cheng J, Ren H, Zhuang H, Sun J, Li L, Li J, Meng Q, Zhao J, Duan Z, Jia J, Tang H, Sheng J, Peng J, Lu F, Xie Q, Wei L; Chinese Society of Hepatology, Chinese Medical Association; Chinese Society of Infectious Diseases, Chinese Medical Association. Guideline of prevention and treatment for chronic hepatitis B (2015 Update). J Clin Transl Hepatol 2017; 5(4): 297–318

[44] National Health Commission of the People’s Republic of China. Reply to the No. 3268 of the Fourth Session of the Twelfth National People's Congress. 2016 (in Chinese) http://www.nhfpc.gov.cn/zwgk/jianyi/201611/2f1b4892160040c4ac3ba3eccfc2873d.shtml (accessed April 23, 2018)

[45] Liu J, Liu M. Progress and challenges in achieving the WHO goal on ‘Elimination of Hepatitis B by 2030’ in China. Chin J Epidemiol (Zhonghua Liu Xing Bing Xue Za Zhi) 2019; 40(6): 605–609 (in Chinese)

[46] Ministry of Human Resources and Social Security of the People’s Republic of China. National Basic Medical Insurance, Industrial Injury Insurance and Maternity Insurance Drug List (2017 Edition). 2017 (in Chinese) http://www.mohrss.gov.cn/SYrlzyhshbzb/shehuibaozhang/zcwj/201702/t20170223_266775.html (accessed March 29, 2018)

[47] Zhao H, Ma X, Zhang L, Liu X, Ciren L, Song C. Status of hepatitis B virus infection in pregnant women and infants in Ali, Tibet. China Trop Med (Zhongguo Re Dai Yi Xue) 2018; 18(12): 1218–1221 (in Chinese)

[48] Cui F, Woodring J, Chan P, Xu F. Considerations of antiviral treatment to interrupt mother-to-child transmission of hepatitis B virus in China. Int J Epidemiol 2018; 47(5): 1529–1537

[49] Li G, Chen J, Xie Z, Li X, Zhang Y, Zhang J. HBsAg screening results of 10018 cases of pregnant women, Yunnan, 2013–2016. Mod Prev Med (Xian Dai Yu Fang Yi Xue) 2018; 45(13): 2350–2353, 2441 (in Chinese)

[50] National Health Commission of the People’s Republic of China. WHO awards recognition for the prevention and control of hepatitis B in children in China. 2014 (in Chinese) http://www.nhfpc.gov.cn/gjhzs/ptpxw/201402/0f6349b5c3c243f89238e8d84c17bed0.shtml (accessed April 20, 2018)

[51] National Health Commission of the People’s Republic of China. National maternal and child health monitoring and annual report communication. 2016 (in Chinese) http://www.mchscn.org/Article_Show.asp?ArticleID=651 (accessed July 30, 2018)

[52] Schillie S, Vellozzi C, Reingold A, Harris A, Haber P, Ward JW, Nelson NP. Prevention of hepatitis B virus infection in the United States: recommendations of the Advisory Committee on Immunization Practices. MMWR Recomm Rep 2018; 67(1): 1–31

[53] National Health Commission of the People’s Republic of China. The 2019 China Health Statistics Yearbook. Beijing: China Union Medical University Press, 2019 (in Chinese)

[54] National Health Commission of the People’s Republic of China. National maternal and child health monitoring and annual report communication. 2018 (in Chinese) http://www.mchscn.org/Article_Show.asp?ArticleID=694 (accessed July 30, 2019)

[55] Zhang H, Pan CQ, Pang Q, Tian R, Yan M, Liu X. Telbivudine or lamivudine use in late pregnancy safely reduces perinatal transmission of hepatitis B virus in real-life practice. Hepatology 2014; 60(2): 468–476

[56] Terrault NA, Bzowej NH, Chang KM, Hwang JP, Jonas MM, Murad MH; American Association for the Study of Liver Diseases. AASLD guidelines for treatment of chronic hepatitis B. Hepatology 2016; 63(1): 261–283

[57] Terrault NA, Lok ASF, McMahon BJ, Chang KM, Hwang JP, Jonas MM, Brown RS Jr, Bzowej NH, Wong JB. Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance. Hepatology 2018; 67(4): 1560–1599

[58] European Association for the Study of the Liver. EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection. J Hepatol 2017; 67(2): 370–398

[59] World Health Organization. WHO begins guideline development to stop mother-to-child transmission of hepatitis B. Geneva, Switzerland: World Health Organization, 2019. https://www.who.int/hepatitis/news-events/hbv-mtc-guidelines-development/en/(accessed October 20, 2019)

Acknowledgements

This study was supported by the grant from the National Natural Science Foundation of China (Nos. 71874003, 71934002, and 81703240).

Compliance with ethics guidelines

Wenzhan Jing, Jue Liu, and Min Liu have no conflicts of interest to declare. This manuscript is a review article and does not involve a research protocol requiring approval by a relevant institutional review board or ethics committee.

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