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Hepatitis B surface antigen prevalence and the rates of mother-to-child transmission of hepatitis B virus after the introduction of infant vaccination programs in South East Asia and Western Pacific regions: a systematic review

Open AccessPublished:September 08, 2022DOI:https://doi.org/10.1016/j.ijid.2022.09.003

      HIGHLIGHTS

      • Hepatitis B virus elimination requires <0.1% prevalence of hepatitis B surface antigen in children aged below 5 years by 2030.
      • Since the introduction of hepatitis B vaccines, hepatitis B surface antigen prevalence in children has reduced.
      • This reduction was seen regardless of the vaccination schedule.
      • The strategy to prevent mother-to-child transmission varies between countries.
      • The children of hepatitis B e antigen-positive mothers have a high risk of infection despite vaccination.

      Abstract

      Objectives

      Infant vaccination against the hepatitis B virus began in the World Health Organization South East Asia Region and the Western Pacific Region between 1983 and 2016. This systematic review examined the seroprevalence of hepatitis B surface antigen (HBsAg) in children and the rate of mother-to-child transmission (MTCT) in these regions between 1990 and 2020.

      Methods

      MEDLINE and EMBASE were searched for articles published between January 1990 and September 2020, which reported seroprevalence of HBsAg in children aged 0-15 years and/or the rate of MTCT in the South East Asia Region and Western Pacific Region. A pragmatic review identified supporting information. This review was registered in the International Prospective Register of Systematic Reviews (#CRD42020211707).

      Results

      Of 115 included studies, 77 (24 countries) reported HBsAg prevalence, and 38 (nine countries) reported MTCT. The seroprevalence of HBsAg ranged between 0.0% and 27.4%, with a decreasing trend over time in each country. MTCT rates were 0.0-5.2% in infants of mothers who are hepatitis B e antigen-negative and 2.7-53.0% in infants of mothers who are hepatitis B e antigen-positive.

      Conclusion

      After the introduction of infant hepatitis B virus vaccination programs, the countries in South East Asia Region and Western Pacific Region observed a reduction in HBsAg seroprevalence in children. Nevertheless, the risk of MTCT persists, emphasizing the importance of antenatal screening to identify high-risk pregnancies.

      Keywords

      Abbreviations:

      HBeAg (Hepatitis B e antigen), HBsAg (Hepatitis B surface antigen), HBIG (Hepatitis B immunoglobulin), HBV (Hepatitis B virus), MTCT (Mother-to-child transmission), SEAR (South East Asia Region), WHO (World Health Organization), WPR (Western Pacific Region)

      Introduction

      Hepatitis B virus (HBV) infection incurs a substantial burden worldwide due to the associated cost of prevention, diagnosis, and treatment (
      • Zampino R
      • Boemio A
      • Sagnelli C
      • Alessio L
      • Adinolfi LE
      • Sagnelli E
      • Coppola N.
      Hepatitis B virus burden in developing countries.
      ). Global HBV seroprevalence in 2016 was estimated to be 3.9%, with approximately 296 million people living with chronic HBV infection in 2019 and 1.5 million new infections annually (

      California dental association Foundation Polaris Observatory. Polaris global HBV prevalence estimate for 2016. https://cdafound.org/polaris-regions-dashboard/, 2020 (accessed 4 November 2020).

      ;

      World Health Organization. Global hepatitis report. https://www.who.int/publications/i/item/global-hepatitis-report-2017, 2017 (accessed 4 November 2020).

      ;

      World Health Organization. WHO hepatitis B fact sheet. https://www.who.int/news-room/fact-sheets/detail/hepatitis-b, 2021 (accessed 1 November 2020).

      ). In highly endemic countries, mother-to-child transmission (MTCT) accounts for most new cases (
      • Gentile I
      • Borgia G.
      Vertical transmission of hepatitis B virus: challenges and solutions.
      ).
      In 2016, the World Health Assembly endorsed the ‘Global Health Sector Strategy on Viral Hepatitis 2016-2021’. One goal is to reduce the incidence of chronic HBV infections worldwide, with a target of <0.1% prevalence of hepatitis B surface antigen (HBsAg) carriage in children aged 5 years by the year 2030 (
      World Health Organization
      Global health sector strategy on viral hepatitis 2016–2021.
      ). Estimating the current seroprevalence of HBsAg in children and evaluating the progress toward this target is critical because this may reflect the impact of vaccination programs and be a future indicator of the burden of chronic HBV infection in adults.
      The composition of the HBV vaccine has evolved from a monovalent vaccine to being a component of pentavalent and hexavalent vaccines. Pentavalent vaccines provide immunization against HBV plus four other pathogens: diphtheria, tetanus, and pertussis (DTP) and either Haemophilus influenzae type B (Hib) or inactivated polio virus (IPV); hexavalent vaccines provide immunization against all six. Compared with monovalent HBV vaccines, combination vaccines may be advantageous because they simplify the immunization schedule and increase opportunities to vaccinate (
      • Dodd D.
      Benefits of combination vaccines: effective vaccination on a simplified schedule.
      ), improving vaccination coverage rates, particularly for Hib and HBV (
      • Bairwa M
      • Pilania M
      • Rajput M
      • Khanna P
      • Kumar N
      • Nagar M
      • Chawla S.
      Pentavalent vaccine: a major breakthrough in India's Universal Immunization Program.
      ). The evolution of vaccine development has, in part, led to changes in the infant HBV vaccination schedules used worldwide. To prevent MTCT, the World Health Organization (WHO) recommends that the first dose of HBV vaccine is administered immediately after birth (i.e., birth dose) as a monovalent vaccine. A subsequent dose given at 6-8 weeks aligns with the schedule recommended for the administration of the DTP vaccines, components of pentavalent and hexavalent formulations.
      This systematic review aimed to examine the seroprevalence of HBsAg carriage in children over time and the MTCT rate in infants between 1990 and 2020 in two WHO regions: the South East Asia Region (SEAR) and the Western Pacific Region (WPR).
      A secondary objective was to evaluate the impact of a change in the timing of the second HBV vaccine dose from 1 month to 2 months of age on the seroprevalence of HBsAg in children.

      Methods

      Search strategy

      The study protocol was preregistered in the International Prospective Register of Systematic Reviews (#CRD42020211707). The study was reported in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses statement (Supplementary Table S1) (
      • Moher D
      • Liberati A
      • Tetzlaff J
      • Altman DG
      • Group PRISMA
      Preferred Reporting Items for Systematic Reviews and Meta-Analyses: the PRISMA statement.
      ). The following electronic databases were systematically searched for articles published from January 1, 1990 to September 11, 2020: Ovid MEDLINE, MEDLINE In-Process Citations & Daily Update, and EMBASE. The detailed search strategy is available in Supplementary Table S2. A manual search of references in published systematic reviews and websites of health authorities was also conducted.

      Eligibility criteria

      The search included observational studies (cohort and cross-sectional studies) published in any language from 1990 onwards that reported: (i) the seroprevalence of HBsAg in children aged between 0 and 15 years or (ii) the rate of MTCT of HBV. For studies published between 1990 and 2017, only full-text articles were included; for those more recently published (2018-2020), both full-text articles and conference abstracts were included. Studies were excluded if they restricted participants to only healthy individuals or included only selective high-risk populations.

      The countries of interest were

      SEAR: Bangladesh, Bhutan, Democratic People's Republic of Korea, India, Indonesia, Maldives, Myanmar, Nepal, Sri Lanka, Thailand, and Timor-Leste.
      WPR: Australia, Brunei Darussalam, Cambodia, China, Cook Islands, Fiji, Hong Kong, Japan, Kiribati, Lao People's Democratic Republic, Malaysia, Marshall Islands, Micronesia, Mongolia, Nauru, New Zealand, Palau, Papua New Guinea, Philippines, Republic of Korea, Singapore, Solomon Islands, Taiwan, Tonga, Tuvalu, Vanuatu, and Vietnam.

      Screening and data extraction

      Two reviewers (ZM and CW) independently screened titles and abstracts of all publications identified through the electronic database search and independently reviewed potentially eligible full-text articles. Any disagreement was resolved by discussion.
      To examine time trends in HBsAg seroprevalence, the following data were extracted: HBsAg seroprevalence; the age range of included children; the data collection period; and whether studies were representative of the entire country, a region, or a single city. For studies reporting MTCT rates, the estimates were stratified by maternal hepatitis B e antigen (HBeAg) seropositivity. When reported, the following data were also extracted: the number of doses and administration schedule for hepatitis B immunoglobulin (HBIG) and the timing of HBV vaccination.
      The seroprevalence of HBsAg was recorded as the percentage of children who are HBsAg-positive in the population. The rate of MTCT of HBV was defined as the percentage of infants born to mothers infected with HBV who were HBsAg-positive at age 6-12 months.

      Risk of bias and quality assessment

      The risk of bias was assessed using a modified Newcastle-Ottawa scale for quality assessment of cross-sectional and cohort studies (
      • Wells G
      • Shea B
      • O'Connell D
      • Peterson J
      The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses.
      ) in two domains: (i) selection of study groups and (ii) ascertainment of outcomes of interest (Supplementary File S3).

      Pragmatic review

      A pragmatic review identified information on the history of HBV vaccination, vaccine type, schedules, and vaccination coverage rates in each country. This process included a combination of electronic searches and free-text searching of databases and government websites.

      Results

      The pragmatic search identified HBV vaccination schedules across 38 countries in the WHO SEAR and WPR, including the year that infant HBV vaccination was reported to begin (for any population), the year that nationwide vaccination for all infants began, and the year an HBV birth dose was introduced. The World Bank income level for each country is also reported (Table 1, Supplementary Table S7).
      Table 1Summary of HepB vaccination in South East Asia and Western Pacific Regions.
      Country or territoryWorld Bank income group
      World bank income group, June 2020.
      Year infant HepB vaccination startedYear infant HepB vaccination introduced nationwideYear HepB birth dose introducedCurrent (2020) infant HepB vaccines in national vaccination programme
      Monovalent HepB vaccine for birth dose when recommended.
      Current (2020) national HepB vaccination schedule
      South East Asia
      BangladeshLower middle20032005No birth doseDTwP-Hib-HepB6, 10, 14 weeks
      BhutanLower middle199719972012DTaP-Hib-HepB0, 6, 10, 14 weeks
      Democratic People's Republic of KoreaLow2003Unclear, by at least 20132004DTwP-Hib-HepB0, 6, 10, 14 weeks
      IndiaLower middle20022011-20122011 - 2012DTwP-Hib-HepB0, 6, 10, 14 weeks
      IndonesiaUpper middle199719971999, all islands 2002DTwP-Hib-HepB0, 2, 3, 4 months
      MaldivesUpper middle199319932000DTwP-Hib-HepB0, 2, 4, 6 months
      MyanmarLower middle2003Unclear, by at least 20122003 – 2009

      2016
      DTwP-Hib-HepB0, 2, 4, 6 months
      NepalLower middle20022002No birth doseDTwP-Hib-HepB6, 10, 14 weeks
      Sri LankaLower middle20032003No birth doseDTwP-Hib-HepB2, 4, 6 months
      ThailandUpper middle199219921992DTwP-Hib-HepB0, 2, 4, 6 months
      Timor-LesteLower middle200720072016DTwP-Hib-HepB0, 6, 10, 14 weeks
      Western Pacific
      AustraliaHigh198620001986DTaP-IPV-Hib-HepB0, 2, 4, 6 months
      Brunei DarussalamHigh198819881988DTaP-IPV-Hib-HepB0, 2, 4,6 months
      CambodiaLower middle200120052005DTwP-Hib-HepB0, 6, 10, 14 weeks
      ChinaUpper middle199219921992HepB0, 1, 6 months
      Cook IslandsNR19891989Unclear, before 2013DTaP-Hib-HepB0, 6 weeks, 3, 5 months
      FijiUpper middle198919951989DTwP-Hib-HepB0, 6, 10, 14 weeks
      Hong KongHigh198219881988HepB0, 1, 6 months
      JapanHigh198620162015, only if mother HBsAg
      Conflicting reports.
      HepB2, 3, 7 months
      KiribatiLower middle198919951990DTwP-Hib-HepB0, 6, 10, 14 weeks
      Lao PDRLower middle200120042004 - 2006DTwP-Hib-HepB0, 6, 10, 14 weeks
      MalaysiaUpper middle198919891989DTaP-IPV-Hib-HepB0, 2, 3, 5 months
      Marshall IslandsUpper middle199319931998/ 2003DTaP-IPV-HepB0, 2, 4, 6 months
      MicronesiaLower middle198819881988DTaP-IPV-HepB0, 2, 4, 6 months
      MongoliaLower middle199119911991DTwP-Hib-HepB0, 2, 3, 4 months
      NauruHigh19831983Unclear, before 1987DTwP-Hib-HepB0, 6, 10, 14 weeks
      New ZealandHigh198519881987, only if mother HBsAg+DTaP-IPV-Hib-HepB6 weeks, 3, 5 months
      PalauHigh198919891989DTaP-IPV-HepB0, 2, 6 months
      Papua New GuineaLower middle198919892002DTwP-Hib-HepB0, 1, 2, 3 months
      PhilippinesLower middle199119922007DTwP-Hib-HepB0, 6, 10, 14 weeks
      Republic of KoreaHigh198319951983HepB0, 1, 6 months
      SingaporeHigh198319871987DTaP-IPV-Hib-HepB0, 2, 6 months
      Solomon IslandsLower middle199019901990DTwP-Hib-HepB0, 6, 10, 14 weeks
      TaiwanHigh198419861984HepB0, 1, 6 months
      TongaUpper middle198819881988DTwP-Hib-HepB0, 6, 10, 14 weeks
      TuvaluUpper middle199319931993DTwP-Hib-HepB0, 6, 10, 14 weeks
      VanuatuLower middle1989-1993
      Conflicting reports.
      1989-1993
      Conflicting reports.
      1993DTwP-Hib-HepB0, 6, 10, 14 weeks
      VietnamLower middle199720022003DTwP-Hib-HepB0, 2, 3, 4 months
      aP, acellular pertussis; DT, diphtheria, tetanus; HBsAg, hepatitis B surface antigen; HepB, Hepatitis B; Hib, Haemophilus influenzae type B; NR, not reported; PDR, People's Democratic Republic; wP, whole-cell pertussis.
      a World bank income group, June 2020.
      b Monovalent HepB vaccine for birth dose when recommended.
      c Conflicting reports.
      Hepatitis B (HepB) infant vaccination was introduced nationwide between 1992 and 2011 in the SEAR, with unclear information for two of the 11 countries, and between 1983 and 2016 in the 27 countries in the WPR. Four countries in the SEAR and 21 countries in the WPR had introduced nationwide HBV vaccination before the year 2000 (Table 1, Supplementary Table S7).
      At the time of the introduction of HBV vaccines into national immunization programs, most countries exclusively used monovalent HBV vaccines. Pentavalent whole-cell pertussis (wP) DTwP-Hib-HepB vaccines were gradually introduced in the SEAR and WPR, followed by hexavalent acellular pertussis (aP) DTaP-IPV-HepB-Hib vaccines in five countries, all in the WPR (Australia, Brunei Darussalam, Malaysia, New Zealand, and Singapore). Three countries (Marshall Islands, Micronesia, and Palau) currently administer a DTaP-IPV-HepB pentavalent vaccine.
      Bangladesh, Nepal, and Sri Lanka (SEAR) do not administer a birth dose of the HBV vaccine. Japan and New Zealand (WPR) have opted for a selective birth dose, given to infants of mothers who are HBsAg-positive only. All other included countries had introduced a universal birth dose of the HBV vaccine by 2016.
      All countries give at least three HBV vaccination doses to all infants, irrespective of maternal HBV status, with differing schedules. A vaccination schedule of 0, 1, and 6 months is currently in use in countries and territories which continue to exclusively administer a monovalent HBV vaccine. Countries that have integrated combination vaccines into their infant vaccination regimen generally administer a birth dose of monovalent HBV vaccine followed by three doses of HBV-containing pentavalent or hexavalent vaccines in the first 6 months of life. The most common schedules currently in use are 0, 6, 10 and 14 weeks (n = 14 countries), 0, 2, 4 and 6 months (n = 7), and 0, 1 and 6 months (n = 4).
      Estimated vaccination coverage for HBV vaccine birth dose in 2019 was <90% in 13 countries: eight of 24 reporting countries in the WPR and five of eight reporting countries in the SEAR. The vaccination coverage rate for HBV third dose was <90% in eight countries in 2019: six in the WPR and two in the SEAR (
      • UNICEF
      UNICEF Immunization Coverage Data.
      ).
      These countries have varied income levels, with one country in the low-income group, 17 lower-middle, nine upper-middle, and 10 in the high-income group. All 10 high-income countries are in the WPR (Table 1) (
      World Bank World Bank Country and Lending Groups
      ).
      The systematic literature review identified a total of 7148 articles after deduplication. After title and abstract screening, 466 articles were evaluated for full-text review, and three additional articles were identified through hand searching; a total of 115 studies met inclusion criteria (Figure 1). A list of the studies excluded at full-text screening and the reasons for exclusion are in Supplementary Table S4. Risk of bias assessment of the 77 cross-sectional studies identified 25 with a high risk, 48 with medium risk, and four with low risk of bias. Of the 38 cohort studies, 14 had high risk, 13 had medium risk, and 11 had low risk of bias; results for all studies are presented in Supplementary Tables S5 and S6.
      Figure 1
      Figure 1Flow of information through the different phases of the systematic review, adapted from
      • Moher D
      • Liberati A
      • Tetzlaff J
      • Altman DG
      • Group PRISMA
      Preferred Reporting Items for Systematic Reviews and Meta-Analyses: the PRISMA statement.
      .
      A total of 77 studies from 24 countries reported HBsAg prevalence in children, and 38 studies from nine countries reported HBV MTCT rates. The majority of reported data were from national studies, with only Indonesia, Japan, Marshall Islands, and Micronesia reporting results solely from single-city or regional studies. No studies were identified from Brunei Darussalam, Democratic People's Republic of Korea, Maldives, Myanmar, Nauru, New Zealand, Palau, Singapore, Sri Lanka, Timor-Leste, or Tuvalu.
      The seroprevalence of HBsAg in children aged 0-15 years reported from 1990 to 2000 in the 24 countries ranged from 0.0 to 27.4% (Table 2). Full seroprevalence data from all studies are presented in Supplementary Table S8. Countries with the highest levels of HBsAg seroprevalence since 1990 were all part of the WPR and included China (24.2%), Kiribati (27.4%), Mongolia (9.3%), Tonga (11.1%), and Vanuatu (16.3%) (
      • Davaalkham D
      • Ojima T
      • Nymadawa P
      • Tsend N
      • Lkhagvasuren T
      • Wiersma S
      • Uehara R
      • Watanabe M
      • Oki I
      • Nakamura Y.
      Seroepidemiology of hepatitis B virus infection among children in Mongolia: results of a nationwide survey.
      ;
      • Li L
      • He J
      • Zhao L.
      Epidemiologic features of viral hepatitis in Fujian.
      ;
      • Wilson N
      • Ruff TA
      • Rana BJ
      • Leydon J
      • Locarnini S.
      The effectiveness of the infant hepatitis B immunisation program in Fiji, Kiribati, Tonga and Vanuatu.
      ). A decreasing trend in seroprevalence was observed in 10 studies that compared seroprevalence in children at multiple timepoints; seven studies from China; and one each from Japan, Malaysia, and Taiwan (
      • 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.
      ;
      • Hsu HM
      • Lu CF
      • Lee SC
      • Lin SR
      • Chen DS.
      Seroepidemiologic survey for hepatitis B virus infection in Taiwan: the effect of hepatitis B mass immunization.
      ;
      • Kang W Y
      • Tian Z
      • Li Q
      • Zhang L
      • Xu L.
      Sero-epidemiological survey on hepatitis B virus in Yunnan Province, between 2006 and 2014.
      ;
      • Liu J
      • Lv J
      • Yan B
      • Feng Y
      • Song L
      • Xu A
      • Zhang L
      • Yan Y.
      Comparison between two population-based hepatitis B serosurveys with an 8-year interval in Shandong Province, China.
      ;
      • Ng KP
      • Saw TL
      • Baki A
      • Rozainah K
      • Pang KW
      • Ramanathan M.
      Impact of the Expanded Program of Immunization against hepatitis B infection in school children in Malaysia.
      ;
      • Noto H
      • Terao T
      • Ryou S
      • Hirose Y
      • Yoshida T
      • Ookubo H
      • Mito H
      • Yoshizawa H
      Special Committee for Preventing Hepatitis B in Shizuoka. Combined passive and active immunoprophylaxis for preventing perinatal transmission of the hepatitis B virus carrier state in Shizuoka, Japan during 1980–1994.
      ;
      • Tao Y
      • Yan L
      • Wang C
      • Xu H
      • Zhang J
      • Yu JX.
      Seroprevalence of hepatitis B in populations at ages of 1–59 years in Changchun City, Jilin Province, China in 2006 and 2016.
      ;
      • Wang FZ
      • Zhang GM
      • Shen LP
      • Zheng H
      • Wang F
      • Miao N
      • Yuan QL
      • Sun XJ
      • Bi SL
      • Liang XF
      • Wang HQ.
      [Comparative analyze on hepatitis B seroepidemiological surveys among population aged 1–29 years in different epidemic regions of China in 1992 and 2014].
      ,
      • Wang FZ
      • Zheng H
      • Miao N
      • Sun XJ
      • Zhang GM
      • Liang XF
      • Cui FQ.
      [Analysis on sero-epidemiological characteristics of hepatitis B virus among people born during 1994–2001 before and after hepatitis B vaccine catch-up vaccination, China].
      ;
      • Zhou Y
      • He H
      • Deng X
      • Yan R
      • Tang X
      • Xie S
      • Yao J.
      Significant reduction in notification and seroprevalence rates of hepatitis B virus infection among the population of Zhejiang Province, China, aged between 1 and 29 years from 2006 to 2014.
      ). Lower seroprevalence was also consistently reported in younger children than in older children (Supplementary Table S8).
      Table 2Summary of HBsAg prevalence in children aged 0-15 years, by country or territory.
      Country or territoryNumber of studies identifiedAge range of children in studiesHBsAg prevalence
      %Data periodStudy coverage
      South East Asia
      Bangladesh1 (
      • Paul RC
      • Rahman M
      • Wiesen E
      • Patel M
      • Banik KC
      • Sharif AR
      • Sultana S
      • Rahman M
      • Liyanage J
      • Abeysinghe N
      • Kamili S
      • Murphy T
      • Luby SP
      • Mast EE.
      Hepatitis B surface antigen seroprevalence among prevaccine and vaccine era children in Bangladesh.
      )
      4–7 years0.1%2011–2012National
      8–11 years1.2%
      Bhutan1 (
      • Tshering N
      • Dhakal GP
      • Wangchuk U
      • Wangdi S
      • Khandu L
      • Pelden S
      • Nogareda F
      • Patel MK
      • Hutin YJF
      • Wannemuehler K
      • Rewari BB
      • Wangchuk S.
      Prevalence of HBV and HCV infections, Bhutan, 2017: progress and next steps.
      )
      1–4 years0.0%2017National
      India1 (
      • Murhekar MV
      • Santhosh Kumar M
      • Kamaraj P
      • Khan SA
      • Allam RR
      • Barde P
      • Dwibedi B
      • Kanungo S
      • Mohan U
      • Mohanty SS
      • Roy S
      • Sagar V
      • Savargaonkar D
      • Tandale BV
      • Topno RK
      • Kumar CPG
      • Sabarinathan R
      • Bitragunta S
      • Grover GS
      • Lakshmi PVM
      • Mishra CM
      • Sadhukhan P
      • Sahoo PK
      • Singh SK
      • Yadav CP
      • Kumar R
      • Dutta S
      • Toteja GS
      • Gupta N
      • Mehendale SM
      ICMR – Serosurvey group. Hepatitis-B virus infection in India: findings from a nationally representative serosurvey, 2017–18.
      )
      5–10 years0.7%2017National
      Indonesia2 (
      • Achwan WA
      • Muttaqin Z
      • Zakaria E
      • Depamede SA
      • Mulyanto SS
      • Tsuda F
      • Takahashi K
      • Abe N
      • Mishiro S.
      Epidemiology of hepatitis B, C, and E viruses and human immunodeficiency virus infections in Tahuna, Sangihe-Talaud archipelago, Indonesia.
      ;
      • Purwono PB
      • Juniastuti Amin M
      • Bramanthi R
      • Nursidah Resi EM
      • Wahyuni RM
      • Yano Y
      • Soetjipto Hotta H
      • Hayashi Y
      • Utsumi T
      • Lusida MI
      Hepatitis B virus infection in Indonesia 15 years after adoption of a universal infant vaccination program: possible impacts of low birth dose coverage and a vaccine-escape mutant.
      )
      1–15 years0.0%2005City
      1–5 years (min/max)2.1%/4.2%2012City
      6–12 years (min/max)0.0%/5.9%
      Nepal1 (
      • Upreti SR
      • Gurung S
      • Patel M
      • Dixit SM
      • Krause LK
      • Shakya G
      • Wannemuehler K
      • Rajbhandari R
      • Bohara R
      • William Schluter W.
      Prevalence of chronic hepatitis B virus infection before and after implementation of a hepatitis B vaccination program among children in Nepal.
      )
      5–6 years0.1%2012National
      10–12 years0.3%
      Thailand3 (
      • Chunsuttiwat S
      • Biggs BA
      • Maynard J
      • Thamapalo S
      • Laoboripat S
      • Bovornsin S
      • Charanasri U
      • Pinyowiwat W
      • Kunasol P.
      Integration of hepatitis B vaccination into the expanded programme on immunization in Chonburi and Chiangmai provinces, Thailand.
      ;
      • Jutavijittum P
      • Jiviriyawat Y
      • Yousukh A
      • Hayashi S
      • Toriyama K.
      Evaluation of a hepatitis B Vaccination Program in Chiang Mai.
      ;
      • Posuwan N
      • Wanlapakorn N
      • Sa-Nguanmoo P
      • Wasitthankasem R
      • Vichaiwattana P
      • Klinfueng S
      • Vuthitanachot V
      • Sae-Lao S
      • Foonoi M
      • Fakthongyoo A
      • Makaroon J
      • Srisingh K
      • Asawarachun D
      • Owatanapanich S
      • Wutthiratkowit N
      • Tohtubtiang K
      • Yoocharoen P
      • Vongpunsawad S
      • Poovorawan Y.
      The success of a universal hepatitis B immunization program as part of Thailand's EPI after 22 years’ implementation.
      )
      7 months–5 years2.9%1991Regional
      0.8%1993
      4–5 years0.4%1998–2000Regional
      6–7 years0.9%
      8–9 years2.2%
      0.5–5 years0.1%2014National
      5–10 years0.3%
      Western Pacific
      Australia2 (
      • Burgess MA
      • McIntosh EDG
      • Allars HM
      • Kenrick KG.
      Hepatitis B in urban Australian schoolchildren. No evidence of horizontal transmission between high-risk and low-risk groups.
      ;
      • O'Sullivan BG
      • Gidding HF
      • Law M
      • Kaldor JM
      • Gilbert GL
      • Dore GJ.
      Estimates of chronic hepatitis B virus infection in Australia, 2000.
      11–12 years1.9%1990–1991City
      1–9 years0.0%1996–1999National
      10–14 years0.2%
      Cambodia5 (
      • Ko K
      • Takahashi K
      • Nagashima S
      • Yamamoto C
      • Ork V
      • Sugiyama A
      • Akita T
      • Ohisa M
      • Chuon C
      • Hossain MS
      • Mao B
      • Tanaka J.
      Existence of hepatitis B virus surface protein mutations and other variants: demand for hepatitis B infection control in Cambodia.
      ;
      • Mao B
      • Patel MK
      • Hennessey K
      • Duncan RJ
      • Wannemuehler K
      • Soeung SC.
      Prevalence of chronic hepatitis B virus infection after implementation of a hepatitis B vaccination program among children in three provinces in Cambodia.
      ;
      • Ork V
      • Woodring J
      • Md Shafiqul Hossain
      • Wasley A
      • Nagashima S
      • Yamamoto C
      • Chuon C
      • Sugiyama A
      • Ohisa M
      • Akita T
      • Ko K
      • Mao B
      • Tanaka J
      Hepatitis B surface antigen seroprevalence among pre- and post-vaccine cohorts in Cambodia, 2017.
      ;
      • Soeung SC
      • Rani M
      • Huong V
      • Sarath S
      • Kimly C
      • Kohei T
      Results from nationwide hepatitis B serosurvey in Cambodia using simple and rapid laboratory test: implications for national immunization program.
      ;
      • Tanaka J
      • Woodring JV
      • Ork V
      • Bunsoth M
      • Nagashima S
      • Yamamoto C
      • Choun C
      • Ko K
      • Hossain S.
      Sero-prevalence of hepatitis B surface antigen among 5–7 years old children and their mothers in Cambodia by nationwide multistage stratified random sampling strategy.
      )
      5–7 years0.5-0.8%NRNational
      5 years3.5%2006National
      4–5 years0.33%2011City
      5–7 years0.52%2017National
      5–7 years0.56%2017National
      China
      Only prevalence data from nationally representative studies are presented due to the large number of included studies from China. All studies are presented in Supplementary Table S8. HBsAg, hepatitis B surface antigen.
      45 (
      • Cheng JQ
      • Ma HW
      • Xie X
      • Lu Y
      • Zhang YB
      • Dong SX
      • Wang T
      • Liu Y
      • Ling W
      • Hao Y.
      Sero-epidemiological investigation on hepatitis B among permanent residents in Shenzhen area.
      ;
      • 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.
      ;
      • Dong Y
      • Liu SL
      • Zhai XJ
      • Zhu FC
      • Pan H
      • Yu JX
      • Chen YZ
      • Xie YR
      • Zhang XY
      • Zhang HM
      • Li LJ
      • Wang H
      • Ruan B.
      A serological and molecular survey of hepatitis B in children 15 years after inception of the national hepatitis B vaccination program in eastern China.
      ;
      • Du F
      • Liu QL
      • Fu QP
      • Sun L
      • Ao R
      • Guan XJ
      • et al.
      A seroepidemiologic analysis of hepatitis B in Sichuan province.
      • Gao P
      • Wang H
      • Chen WX
      • Sun YN
      • Zhang W
      • Pang XH
      • He X
      • Wu J.
      A sero-epidemiological study of hepatitis B among general population in Beijing.
      ;
      • Gong XH
      • Liu LR
      • Jia L
      • Li YH
      • Xing YL
      • Wang QY.
      [Epidemiological effect of hepatitis B immunization among newborn babies in Beijing].
      ,
      • Gong XH
      • Wang FZ
      • Li H
      • Liu LR
      • Li YH
      • Wang BL
      • Li LQ
      • Zhang Z
      • Han QY
      • Tang TW.
      Observation on effects of hepatitis B vaccine immunization for 12 years in children in Beijing.
      ;
      • Huang P
      • Zhu LG
      • Zhu YF
      • Yue M
      • Su J
      • Zhu FC
      • Yang HT
      • Zhang Y
      • Shen HB
      • Yu RB
      • Zhai XJ
      • Peng ZH.
      Seroepidemiology of hepatitis B virus infection and impact of vaccination.
      ;
      • Ji Z
      • Wang T
      • Shao Z
      • Huang D
      • Wang A
      • Guo Z
      • Long Y
      • Zhang L
      • Su H
      • Zhang Q
      • Yan Y
      • Fan D.
      A population-based study examining hepatitis B virus infection and immunization rates in Northwest China.
      ;
      • Kang W Y
      • Tian Z
      • Li Q
      • Zhang L
      • Xu L.
      Sero-epidemiological survey on hepatitis B virus in Yunnan Province, between 2006 and 2014.
      ;
      • Li L
      • He J
      • Zhao L.
      Epidemiologic features of viral hepatitis in Fujian.
      ,
      • Li YC
      • Zhu XJ
      • Zhang ZL.
      [Study on the status of HBV infection and influencing factors in a population aged 1 to 59 years old in Tianjin].
      ;
      • Li X
      • Zheng Y
      • Liau A
      • Cai B
      • Ye D
      • Huang F
      • et al.
      Hepatitis B virus infections and risk factors among the general population in Anhui Province, China: an epidemiological study.
      ;
      • Liang X
      • Bi S
      • Yang W
      • Wang L
      • Cui G
      • Cui F
      • et al.
      Epidemiological serosurvey of hepatitis B in China—declining HBV prevalence due to hepatitis B vaccination.
      ,
      • 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.
      ,
      • Liang XF
      • Chen YS
      • Wang XJ
      • He X
      • Chen LJ
      • Wang J
      • Lin C
      • Bai H
      • Yan J
      • Cui G
      • Yu J.
      [A study on the sero-epidemiology of hepatitis B in Chinese population aged over 3-years old].
      ;
      • Liu J
      • Lv J
      • Yan B
      • Feng Y
      • Song L
      • Xu A
      • Zhang L
      • Yan Y.
      Comparison between two population-based hepatitis B serosurveys with an 8-year interval in Shandong Province, China.
      ;
      • Liu XJ
      • Li WL
      • Peng YY
      • Wang J
      • Ren T
      • Wang LP
      • Yuan P.
      Prevalence of hepatitis B surface antigens and hepatitis B surface antibodies in 1–12 years-old children in Mianyang, Sichuan.
      ;
      • Lu J
      • Li H
      • Tian R
      • Jiang Y
      • Xu Y
      • Yu D
      • Jiang J
      • Bi S.
      Hepatitis viruses infection situation in human population of the Gansu province.
      ,
      • Lu J
      • Zhou Y
      • Lin X
      • Jiang Y
      • Tian R
      • Zhang Y
      • Wu J
      • Zhang F
      • Zhang Y
      • Wang Y
      • Bi S.
      General epidemiological parameters of viral hepatitis A, B, C, and E in six regions of China: a cross-sectional study in 2007.
      ;
      • Shao X
      • Wu C
      • Wang F
      • Liang J
      • Xie X
      • Zhu Q
      • Liu J
      • Hu P
      • Qiu Q
      • Liang X
      • Zheng H.
      Seroepidemiological analysis of hepatitis B among children aged 1–14 in 3 counties of Guangdong Province in 2013.
      ;
      • Su H
      • Shao Z
      • Pu Z
      • Wang Y
      • Zhang L
      • Zhang W
      • Wang B
      • Wang A
      • Ji Z
      • Yan Y
      • Zhang Y
      Overt and occult hepatitis B virus infection among community children in Northwest China.
      ;
      • Tao Y
      • Yan L
      • Wang C
      • Xu H
      • Zhang J
      • Yu JX.
      Seroprevalence of hepatitis B in populations at ages of 1–59 years in Changchun City, Jilin Province, China in 2006 and 2016.
      ;
      • Wang F
      • Kang W
      • Zhou W
      • Su Q
      • Bi S
      • Qiu F
      • Li Q.
      Investigation of the risk factors associated with the failure of hepatitis B vaccination of neonates in Yunnan Province, China.
      ;
      • Wang S
      • Tao Y
      • Tao Y
      • Jiang J
      • Yan L
      • Wang C
      • Ding Y
      • Yu J
      • Zhao D
      • Chi X
      • Wang X
      • Wu R
      • Gao X
      • Shi Y
      • Guan Y
      • Li Y
      • Xing Y
      • Sun H
      • Ta C
      • Wang C
      • Niu J
      • Meng J
      • Xu H
      Epidemiological study of hepatitis B and hepatitis C infections in northeastern China and the beneficial effect of the vaccination strategy for hepatitis B: a cross-sectional study.
      ;
      • Wang FZ
      • Zhang GM
      • Shen LP
      • Zheng H
      • Wang F
      • Miao N
      • Yuan QL
      • Sun XJ
      • Bi SL
      • Liang XF
      • Wang HQ.
      [Comparative analyze on hepatitis B seroepidemiological surveys among population aged 1–29 years in different epidemic regions of China in 1992 and 2014].
      ,
      • Wang FZ
      • Zhang GM
      • Shen LP
      • Liu JH
      • Zheng H
      • Wang F
      • Miao N
      • Sun XJ
      • Liang XF
      • Cui FQ.
      Epidemiological characteristics of children aged 1–4 years without timely birth dose of hepatitis B vaccine vaccination in China, 2014.
      ;
      • Wang H
      • Zhang W
      • Ma JX
      • Li LQ
      • Zhang XC
      • Li SM
      • Wu K
      • Li Q
      • Liu X
      • Pang X.
      [Survey on seroepidemiological status and vaccine coverage of hepatitis B among children in Chaoyang district of Beijing in 2010].
      ;
      • Wang X
      • Ding D
      • Sun B.
      [Epidemiological feature of hepatitis B in Zaozhuang City, Shandong Province].
      • Wang FZ
      • Zheng H
      • Miao N
      • Sun XJ
      • Zhang GM
      • Liang XF
      • Cui FQ.
      [Analysis on sero-epidemiological characteristics of hepatitis B virus among people born during 1994–2001 before and after hepatitis B vaccine catch-up vaccination, China].
      ;
      • Wu J
      • Zhang W
      • Han L
      • Lin C
      • Lin H
      • Xing Y
      • Gao P
      • Gong X
      • Liu L
      • Huang F
      • Liu J
      • Liu L
      • Wang H
      • Yu H
      • Liu X
      • Tang Y
      • Pu Y
      • Zhao W
      • Wang C
      • Zhang Z
      • Ma L.
      A sero-epidemiologiecal study on hepatitis B among general population in Beijing.
      • Wu JN
      • Wen XZ
      • Zhou Y
      • Lin D
      • Zhang SY
      • Yan YS.
      Impact of the free-vaccine policy on timely initiation and completion of hepatitis B vaccination in Fujian.
      ;
      • Xi NN
      • Zuo ZL
      • Long SS
      • Ma YJ
      • Zhang JY.
      A cross-sectional study of hepatitis B virus infection in Mianyang, Sichuan Province.
      ;
      • Xia G
      • Liu C
      • Cao H
      • Bi S
      • Zhan M
      • Su C
      • 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.
      ;
      • Xiao J
      • Zhang J
      • Wu C
      • Shao X
      • Peng G
      • Peng Z
      • Ma W
      • Zhang Y
      • Zheng H.
      Impact of hepatitis B vaccination among children in Guangdong Province, China.
      ;
      • Yonghao G
      • Jin X
      • Jun L
      • Pumei D
      • Ying Y
      • Xiuhong F
      • Yanyang Z
      • Wanshen G
      An epidemiological serosurvey of hepatitis B virus shows evidence of declining prevalence due to hepatitis B vaccination in central China.
      ;
      • Zeng F
      • Guo P
      • Huang Y
      • Xin W
      • Du Z
      • Zhu S
      • Deng Y
      • Zhang D
      • Hao Y.
      Epidemiology of hepatitis B virus infection: results from a community-based study of 0.15 million residents in South China.
      ;
      • Zhai RF
      • Guang M
      • Chang SY
      • An JH
      • Li TS
      • Zhao FM
      • Wang HJ
      • Li H
      • Wang XF.
      Serological survey on viral hepatitis B in the population of Shanxi province.
      ;
      • Zhang ZB
      • Xue ZX
      • Han ZG
      • Yang QY
      • Zheng QY
      • Zulipikaer T
      • et al.
      Status of seroepidemiology of hepatitis A, B and C in primary and middle school students in Shufu county, Xinjiang Uygur Autonomous Region of China.
      ;
      • Zhang T
      • Xiao Z
      • Ling H
      • Ge C
      • Ying L
      • Ding Q
      • Kai-Ling X
      • Yan-Ming M
      • Yue-He D
      • Ling-Yang Z
      A community-based sero-epidemiological study of hepatitis B infection in Lianyungang, China, 2010.
      ;
      • Zhang XC
      • Pang XH
      • Zhang W
      • Han LL
      • Lin CY
      • Ma JX
      • Wu K
      • Li SM
      • Wang Q
      • Li L
      • Wang H
      • Gao P.
      [Prevalence of hepatitis B in Chaoyang district, Beijing in 2010].
      ;
      • Zhou LH
      • Li XQ
      • Ye DQ
      • Zheng YJ
      • Ge FY
      • Cai B
      • Huang F.
      A cross-sectional survey on hepatitis B among general population in areas along Yangzi River in Anhui Province.
      ;
      • Zhang XH
      • Wang Q
      • Zheng W
      • Li XH
      • Jiang QQ
      • Zhou CF
      • Qiu LQ.
      [Early physical growth and disease analysis among children born delivered by HBsAg-positive mothers].
      ;
      • Zhang S
      • Li RT
      • Wang Y
      • Liu Q
      • Zhou YH
      • Hu Y.
      Seroprevalence of hepatitis B surface antigen among pregnant women in Jiangsu, China, 17 years after introduction of hepatitis B vaccine.
      ;
      • Zhuo J
      • Tao G
      • Ebrahim SH
      • Wang S
      • Luo Z
      • Wang H.
      The relationship of hepatitis B virus infection between adults and their children in Guangxi Province.
      )
      1–14 years10.39%1992National
      3–4 years3.112002National
      5–9 years4.83%
      10–14 years7.09%
      1–14 years2.1%2006National
      <5 years1.16%2007National
      1–4 years0.31%2014National
      1–12 years10.5%1992National
      0.64%2014
      <15 years10.5%1992National
      10.5%2014
      Cook Islands1 (
      • Patel MK
      • Wannemuehler K
      • Tairi R
      • Tutai R
      • Moturi E
      • Tabwaia B
      • Nikuata AB
      • Etuale MF
      • Mokoia G.
      Progress towards achieving hepatitis B control in the Cook Islands, Niue, Tokelau, and Kiribati.
      )
      6–7 years0.0%2012–2015National
      Fiji1 (
      • Wilson N
      • Ruff TA
      • Rana BJ
      • Leydon J
      • Locarnini S.
      The effectiveness of the infant hepatitis B immunisation program in Fiji, Kiribati, Tonga and Vanuatu.
      )
      12–24 months0.7%1998National
      10–13 years6.9%
      Japan1 (
      • Noto H
      • Terao T
      • Ryou S
      • Hirose Y
      • Yoshida T
      • Ookubo H
      • Mito H
      • Yoshizawa H
      Special Committee for Preventing Hepatitis B in Shizuoka. Combined passive and active immunoprophylaxis for preventing perinatal transmission of the hepatitis B virus carrier state in Shizuoka, Japan during 1980–1994.
      )
      7–12 years0.3%1990Regional
      0.0%2000
      13–15 years0.04%1990
      0.0%2000
      Kiribati2 (
      • Patel MK
      • Wannemuehler K
      • Tairi R
      • Tutai R
      • Moturi E
      • Tabwaia B
      • Nikuata AB
      • Etuale MF
      • Mokoia G.
      Progress towards achieving hepatitis B control in the Cook Islands, Niue, Tokelau, and Kiribati.
      ;
      • Wilson N
      • Ruff TA
      • Rana BJ
      • Leydon J
      • Locarnini S.
      The effectiveness of the infant hepatitis B immunisation program in Fiji, Kiribati, Tonga and Vanuatu.
      )
      12–24 months3.8%1998National
      10–13 years27.4%
      5–6 years3.3%2012–2015National
      Lao People's Democratic Republic3 (
      • Black AP
      • Nouanthong P
      • Nanthavong N
      • Souvannaso C
      • Vilivong K
      • Jutavijittum P
      • Samountry B
      • Lütteke N
      • Hübschen JM
      • Goossens S
      • Quet F
      • Buisson Y
      • Muller CP.
      Hepatitis B virus in the Lao People's Democratic Republic: a cross sectional serosurvey in different cohorts.
      ;
      • Komada K
      • Sugiyama M
      • Vongphrachanh P
      • Xeuatvongsa A
      • Khamphaphongphane B
      • Kitamura T
      • Kiyohara T
      • Wakita T
      • Oshitani H
      • Hachiya M.
      Seroprevalence of chronic hepatitis B, as determined from dried blood spots, among children and their mothers in central Lao People's Democratic Republic: A multistage, stratified cluster sampling survey.
      ;
      • Xeuatvongsa A
      • Komada K
      • Kitamura T
      • Vongphrachanh P
      • Pathammavong C
      • Phounphenghak K
      • Sisouk T
      • Phonekeo D
      • Sengkeopaseuth B
      • Som-Oulay V
      • Ishii K
      • Wakita T
      • Sugiyama M
      • Hachiya M.
      Chronic hepatitis B prevalence among children and mothers: results from a nationwide, population-based survey in Lao People's Democratic Republic.
      )
      9–16 months0.5%2011–2013National
      5–9 years2.1%2011Regional
      5–9 years1.7%2012National
      Malaysia1 (
      • Ng KP
      • Saw TL
      • Baki A
      • Rozainah K
      • Pang KW
      • Ramanathan M.
      Impact of the Expanded Program of Immunization against hepatitis B infection in school children in Malaysia.
      )
      7–12 years1.6%1997National
      0.3%2003
      Marshall Islands1 (
      • Bialek SR
      • Helgenberger L
      • Fischer GE
      • Bower WA
      • Konelios M
      • Chaine JP
      • Armstrong G
      • Williams IT
      • Bell BP
      Impact of routine hepatitis B immunization on the prevalence of chronic hepatitis B virus infection in the Marshall Islands and the Federated States of Micronesia.
      )
      5–9 years1.8%2007Regional
      Micronesia1 (
      • Bialek SR
      • Helgenberger L
      • Fischer GE
      • Bower WA
      • Konelios M
      • Chaine JP
      • Armstrong G
      • Williams IT
      • Bell BP
      Impact of routine hepatitis B immunization on the prevalence of chronic hepatitis B virus infection in the Marshall Islands and the Federated States of Micronesia.
      )
      2–6 years2.5%2000Regional
      2–9 years1.5%2005
      Mongolia3 (
      • Davaalkham D
      • Ojima T
      • Nymadawa P
      • Tsend N
      • Lkhagvasuren T
      • Wiersma S
      • Uehara R
      • Watanabe M
      • Oki I
      • Nakamura Y.
      Seroepidemiology of hepatitis B virus infection among children in Mongolia: results of a nationwide survey.
      ,
      • Davaalkham D
      • Ojima T
      • Uehara R
      • Watanabe M
      • Oki I
      • Wiersma S
      • Nymadawa P
      • Nakamura Y.
      Impact of the universal hepatitis B immunization program in Mongolia: achievements and challenges.
      ;
      • Ochirbat T
      • Ali M
      • Pagbajab N
      • Erkhembaatar LO
      • Budbazar E
      • Sainkhuu N
      • Tudevdorj E
      • Kuroiwa C.
      Assessment of hepatitis B vaccine-induced seroprotection among children 5–10 years old in Ulaanbaatar, Mongolia.
      )
      7–12 years5.2%2004National
      5–10 years1.1%2006City
      Papua New Guinea1 (
      • Kitau R
      • Datta SS
      • Patel MK
      • Hennessey K
      • Wannemuehler K
      • Sui G
      • Lagani W.
      Hepatitis B surface antigen seroprevalence among children in Papua New Guinea, 2012–2013.
      )
      4–6 years1.4%2012–2013National
      Philippines1 (
      • Lopez AL
      • Ylade M
      • Daag JV
      • Tandoc AO
      • Bonifacio J
      • Sylim PG
      • Sy AK
      • Centeno R
      • Roque Jr, V
      • Ducusin MJ
      Hepatitis B seroprevalence among 5 to 6 years old children in the Philippines born prior to routine hepatitis B vaccination at birth.
      )
      4–5 years0.5%2013National
      5–6 years1.2%
      Solomon Islands1 (
      • Breakwell L
      • Anga J
      • Cooley G
      • Ropiti L
      • Gwyn S
      • Wannemuehler K
      • Woodring J
      • Ogaoga D
      • Martin D
      • Patel M
      • Tohme RA.
      Seroprevalence of chronic hepatitis B virus infection and immunity to measles, rubella, tetanus and diphtheria among schoolchildren aged 6–7 years old in the Solomon Islands, 2016.
      )
      6–7 years3.1%2016National
      Taiwan1 (
      • Hsu HM
      • Lu CF
      • Lee SC
      • Lin SR
      • Chen DS.
      Seroepidemiologic survey for hepatitis B virus infection in Taiwan: the effect of hepatitis B mass immunization.
      )
      6 years6.3%1991National
      1.7%1993
      Tonga1 (
      • Wilson N
      • Ruff TA
      • Rana BJ
      • Leydon J
      • Locarnini S.
      The effectiveness of the infant hepatitis B immunisation program in Fiji, Kiribati, Tonga and Vanuatu.
      )
      12–24 months3.8%1998National
      10–13 years11.1%
      Vanuatu1 (
      • Wilson N
      • Ruff TA
      • Rana BJ
      • Leydon J
      • Locarnini S.
      The effectiveness of the infant hepatitis B immunisation program in Fiji, Kiribati, Tonga and Vanuatu.
      )
      12–24 months3.0%1998National
      10–13 years16.3%
      Vietnam1 (
      • Nguyen TH
      • Vu MH
      • Nguyen VC
      • Nguyen LH
      • Toda K
      • Nguyen TN
      • Dao S
      • Wannemuehler KA
      • Hennessey KA.
      A reduction in chronic hepatitis B virus infection prevalence among children in Vietnam demonstrates the importance of vaccination.
      )
      3–4 years1.6%2011National
      5–7 years2.1%
      8–11 years3.6%
      a Only prevalence data from nationally representative studies are presented due to the large number of included studies from China. All studies are presented in Supplementary Table S8. HBsAg, hepatitis B surface antigen.
      Studies with the objective of comparing HBsAg seroprevalence in cohorts of children born before and after the nationwide introduction of HBV vaccination were reported from Bangladesh, China, Fiji, Kiribati, Nepal, Thailand, Tonga, and Vanuatu (Figure 2). A study in 1998 of infants aged 12-24 months and children aged 10-13 years (born before the vaccination era) in Fiji, Kiribati, Tonga, and Vanuatu demonstrated lower seroprevalence in the 12-24 month-old age group (0.7% vs 6.9% in Fiji, 3.8% vs 27.4% in Kiribati, 3.8% vs 11.1% in Tonga, and 3.0% vs 16.3% in Vanuatu) (
      • Wilson N
      • Ruff TA
      • Rana BJ
      • Leydon J
      • Locarnini S.
      The effectiveness of the infant hepatitis B immunisation program in Fiji, Kiribati, Tonga and Vanuatu.
      ). Similar results were found in China (0.64% in 2014 vs 10.5% in 1992) (
      • Wang FZ
      • Zhang GM
      • Shen LP
      • Zheng H
      • Wang F
      • Miao N
      • Yuan QL
      • Sun XJ
      • Bi SL
      • Liang XF
      • Wang HQ.
      [Comparative analyze on hepatitis B seroepidemiological surveys among population aged 1–29 years in different epidemic regions of China in 1992 and 2014].
      ).
      Figure 2
      Figure 2Hepatitis B surface antigen seroprevalence in children, in studies comparing pre- and postvaccine era cohort.
      HBV MTCT rates were reported by 38 studies; 26 from China (
      • Chen T
      • Wang J
      • Qiu H
      • Yu Q
      • Yan T
      • Qi C
      • Cao F
      • Tian Z
      • Guo D
      • Yao N
      • Yang Y
      • He Y
      • Zhao Y
      • Liu J.
      Different interventional criteria for chronic hepatitis B pregnant women with HBeAg (+) or HBeAg (-): epidemiological data from Shaanxi.
      ;
      • Choi KC
      • Wong CL
      • Ieong KM.
      Effectiveness of Macau hepatitis B vaccination programme for newborns from hepatitis B carrier mother.
      ;
      • Ding Y
      • Sheng Q
      • Ma L
      • Dou X.
      Chronic HBV infection among pregnant women and their infants in Shenyang, China.
      ;
      • Evans AA
      • Cohen C
      • Huang P
      • Qian L
      • London WT
      • Block JM
      • Chen G.
      Prevention of perinatal hepatitis B transmission in Haimen City, China: results of a community public health initiative.
      ;
      • Guo Y
      • Liu J
      • Meng L
      • Meina H
      • Du Y.
      Survey of HBsAg-positive pregnant women and their infants regarding measures to prevent maternal-infantile transmission.
      ;
      • Hu N
      • Xu JN
      • Li F
      • Fu T
      • Wang HR
      • Gao J
      • Zhang L.
      Epidemiology study of intrauterine transmission of HBV in HBsAg-positive parturients in Xi'an.
      ;
      • Kang W
      • Ding Z
      • Shen L
      • Zhao Z
      • Huang G
      • Zhang J
      • Xiong Q
      • Zhang S
      • Zhang S
      • Wang F.
      Risk factors associated with immunoprophylaxis failure against mother to child transmission of hepatitis B virus and hepatitis B vaccination status in Yunnan Province, China.
      ;
      • Kang W
      • Li Q
      • Shen L
      • Zhang L
      • Tian Z
      • Xu L
      • Qiu F
      • Wang F.
      Risk factors related to the failure of prevention of hepatitis B virus mother-to-child transmission in Yunnan, China.
      ;
      • Liu J
      • Xu B
      • Chen T
      • Chen J
      • Feng J
      • Xu C
      • Liu L
      • Hu Y
      • Zhou YH.
      Presence of hepatitis B virus markers in umbilical cord blood: exposure to or infection with the virus?.
      ;
      • 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.
      ;
      • Li F
      • Wang Q
      • Zhang L
      • Su H
      • Zhang J
      • Wang T
      • Huang D
      • Wu J
      • Yan Y
      • Fan D.
      The risk factors of transmission after the implementation of the routine immunization among children exposed to HBV infected mothers in a developing area in northwest China.
      ;
      • Peng TT
      • Cai QE
      • Yang M
      • Chen SP
      • Chen F
      • Wang M
      • Peng L
      • Wong G
      • Shen CG
      • Cheng WB
      • Liu SY
      • Peng YB
      • Peng JH
      • Chen CM
      • Yang LQ
      • Tang YM
      • Xu ZX
      • Liu YX.
      Epidemiological trends and virological traits of hepatitis B virus infection in pregnant women and neonates.
      ;
      • Qiao YP
      • Su M
      • Song Y
      • Wang XY
      • Li Z
      • Li YL
      • Dou LX
      • Wang Q
      • Hann K
      • Zhang GM
      • Huang XN
      • Yang YN
      • Jin X
      • Wang AL
      Outcomes of the national programme on prevention of mother-to-child transmission of hepatitis B virus in China, 2016–2017.
      ;
      • Shao ZJ
      • Zhang L
      • Xu JQ
      • Xu DZ
      • Men K
      • Zhang JX
      • Cui HC
      • Yan YP.
      Mother-to-infant transmission of hepatitis B virus: a Chinese experience.
      ;
      • Su H
      • Zhang Y
      • Xu D
      • Wang B
      • Zhang L
      • Li D
      • Xiao D
      • Li F
      • Zhang J
      • Yan Y
      Occult hepatitis B virus infection in anti-HBs-positive infants born to HBsAg-positive mothers in China.
      ;
      • Wang F
      • Zheng H
      • Zhang G
      • Ding Z
      • Li F
      • Zhong G
      • Chen Y
      • Jia Y
      • Miao N
      • Wu Z
      • Sun X
      • Li L
      • Liang X
      • Cui F.
      Effectiveness of prevention of mother-to-child transmission practice in three provinces of Southern China.
      ,
      • Wang F
      • Zhang G
      • Zheng H
      • Miao N
      • Shen L
      • Wang F
      Post-vaccination serologic testing of infants born to hepatitis B surface antigen positive mothers in 4 provinces of China.
      ;
      • Wang Z
      • Zhang J
      • Yang H
      • Li X
      • Wen S
      • Guo Y
      • Sun J
      • Hou J.
      Quantitative analysis of HBV DNA level and HBeAg titer in hepatitis B surface antigen positive mothers and their babies: HBeAg passage through the placenta and the rate of decay in babies.
      ;
      • Yin Y
      • Wu L
      • Zhang J
      • Zhou J
      • Zhang P
      • Hou H.
      Identification of risk factors associated with immunoprophylaxis failure to prevent the vertical transmission of hepatitis B virus.
      ;
      • Yin X
      • Han G
      • Zhang H
      • Wang M
      • Zhang W
      • Gao Y
      • et al.
      A real world, prospective cohort study on mother-to-child transmission of HBV in China (Shield 01).
      ;
      • Yonghao G
      • Pumei D
      • Jianhui Y
      • Jin X
      • Yanyang Z
      • Zhe W
      A retrospective study of hepatitis B mother-to-child transmission prevention and postvaccination serological test results of infants at risk of perinatal transmission in two counties of middle China.
      ;
      • Zhang L
      • Gui X
      • Fan J
      • Wang B
      • Ji H
      • Yisilafu R
      • Li F
      • Zhou Y
      • Tong Y
      • Kong X
      • Ye P
      • Zong L
      Breast feeding and immunoprophylaxis efficacy of mother-to-child transmission of hepatitis B virus.
      ,
      • Zhang L
      • Gui XE
      • Teter C
      • Zhong H
      • Pang Z
      • Ding L
      • Li F
      • Zhou Y
      • Zhang L.
      Effects of hepatitis B immunization on prevention of mother-to-infant transmission of hepatitis B virus and on the immune response of infants towards hepatitis B vaccine.
      ,
      • Zhang L
      • Gui X
      • Wang B
      • Ji H
      • Yisilafu R
      • Li F
      • et al.
      A study of immunoprophylaxis failure and risk factors of hepatitis B virus mother-to-infant transmission.
      ,
      • Zhang L
      • Gui XE
      • Wang B
      • Fan JY
      • Cao Q
      • Mullane K
      • Liang XL.
      Serological positive markers of hepatitis B virus in femoral venous blood or umbilical cord blood should not be evidence of in-utero infection among neonates.
      ;
      • Zhang XH
      • Wang Q
      • Zheng W
      • Li XH
      • Jiang QQ
      • Zhou CF
      • Qiu LQ.
      [Early physical growth and disease analysis among children born delivered by HBsAg-positive mothers].
      ); three from Japan (
      • Sasagawa Y
      • Yamada H
      • Morizane M
      • Deguchi M
      • Shirakawa T
      • Morioka I
      • Tanimura K.
      Hepatitis B virus infection: prevention of mother-to-child transmission and exacerbation during pregnancy.
      ;
      • Shirakawa T
      • Sasagawa Y
      • Deguchi M
      • Tanimura K
      • Morizane M
      • Morioka I
      • et al.
      Efficacy of maternal screening and perinatal prevention program for hepatitis B.
      ;
      • Sugiyama A
      • Ohisa M
      • Nagashima S
      • Yamamoto C
      • Chuon C
      • Fujii T
      • et al.
      Reduced prevalence of hepatitis B surface antigen positivity among pregnant women born after the national implementation of immunoprophylaxis for babies born to hepatitis B virus-carrier mothers in Japan.
      ); two from Lao People's Democratic Republic (
      • Jutavijittum P
      • Jiviriyawat Y
      • Yousukh A
      • Hayashi S
      • Toriyama K.
      Evaluation of a hepatitis B Vaccination Program in Chiang Mai.
      ;
      • Latthaphasavang V
      • Vanhems P
      • Ngo-Giang-Huong N
      • Sibounlang P
      • Paboriboune P
      • Malato L
      • Keoluangkhot V
      • Thammasack S
      • Salvadori N
      • Khamduang W
      • Steenkeste N
      • Trépo C
      • Dény P
      • Jourdain G.
      Perinatal hepatitis B virus transmission in Lao PDR: a prospective cohort study.
      ); two from Hong Kong (
      • Cheung KW
      • Seto MTY
      • Kan ASY
      • Wong D
      • Kou KO
      • So PL
      • Lau WL
      • Jalal K
      • Chee YY
      • Wong RMS
      • Lee CP
      • Ng EHY.
      Immunoprophylaxis failure of infants born to hepatitis B carrier mothers following routine vaccination.
      ;
      • Tse K
      • Siu SLY
      • Yip KT
      • Chan SM
      • Que TL
      • Lui WYS
      • Chan PS.
      Immuno-prophylaxis of babies borne to hepatitis B carrier mothers.
      ); and one study each from Australia (
      • 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.
      ), Indonesia (
      • Vranckx R
      • Alisjahbana A
      • Meheus A.
      Hepatitis B virus vaccination and antenatal transmission of HBV markers to neonates.
      ), Republic of Korea (
      • Kim JH
      • Kim JS
      • Lee JJ
      • Kim JH
      • Kim SY
      • Jung YK
      • Kwon OS
      • Kim YS
      • Choi DJ
      • Kim JH.
      Survey of perinatal hepatitis B virus transmission after Korean National Prevention Program in a tertiary hospital.
      ), Taiwan (
      • Chen HL
      • Lin LH
      • Hu FC
      • Lee JT
      • Lin WT
      • Yang YJ
      • Huang FC
      • Wu SF
      • Chen SCC
      • Wen WH
      • Chu CH
      • Ni YH
      • Hsu HY
      • Tsai PL
      • Chiang CL
      • Shyu MK
      • Lee PI
      • Chang FY
      • Chang MH.
      Effects of maternal screening and universal immunization to prevent mother-to-infant transmission of HBV.
      ), and Vietnam (
      • Khue PM
      • Thi Thuy Linh N
      • Hai Vinh V
      • Vu Dung L
      • Nguyen Van B.
      Hepatitis B Infection and Mother-to-Child Transmission in Haiphong, Vietnam: A Cohort Study with Implications for Interventions.
      ). When reported, 81-100% of infants in these studies received HBV vaccination, and some also benefited from HBIG. MTCT rates from all included studies, irrespective of maternal HBeAg status, are presented in Supplementary Table S9. In 23 studies, HBV transmission rates reported in infants of mothers who are HBeAg-positive ranged from 2.7-53.0% (Supplementary Table S10). In 18 studies, transmission rates reported in infants of mothers who are HBsAg-positive and HBeAg-negative ranged from 0.0-5.2% (Supplementary Table S11). In seven studies with 100% coverage for both HBV vaccinations, including a birth dose and HBIG, no MTCT was observed from mothers who are HBsAg-positive and HBeAg-negative (
      • Cheung KW
      • Seto MTY
      • Kan ASY
      • Wong D
      • Kou KO
      • So PL
      • Lau WL
      • Jalal K
      • Chee YY
      • Wong RMS
      • Lee CP
      • Ng EHY.
      Immunoprophylaxis failure of infants born to hepatitis B carrier mothers following routine vaccination.
      ;
      • Liu J
      • Xu B
      • Chen T
      • Chen J
      • Feng J
      • Xu C
      • Liu L
      • Hu Y
      • Zhou YH.
      Presence of hepatitis B virus markers in umbilical cord blood: exposure to or infection with the virus?.
      ;
      • Zhang L
      • Gui X
      • Fan J
      • Wang B
      • Ji H
      • Yisilafu R
      • Li F
      • Zhou Y
      • Tong Y
      • Kong X
      • Ye P
      • Zong L
      Breast feeding and immunoprophylaxis efficacy of mother-to-child transmission of hepatitis B virus.
      ,
      • Zhang L
      • Gui XE
      • Teter C
      • Zhong H
      • Pang Z
      • Ding L
      • Li F
      • Zhou Y
      • Zhang L.
      Effects of hepatitis B immunization on prevention of mother-to-infant transmission of hepatitis B virus and on the immune response of infants towards hepatitis B vaccine.
      ,
      • Zhang L
      • Gui X
      • Wang B
      • Ji H
      • Yisilafu R
      • Li F
      • et al.
      A study of immunoprophylaxis failure and risk factors of hepatitis B virus mother-to-infant transmission.
      ). Because there were very few MTCT studies identified outside China, and there was large heterogeneity between studies in terms of data collection period, vaccination coverage, HBIG coverage, and child age at assessment, a meta-analysis to pool the MTCT rates was not performed.
      The percentage of mothers who are HBeAg-positive included in the studies of HBV MTCT ranged from 22.1-67.1% (Supplementary Table S9). There was considerable heterogeneity in the study populations and data collection period, and few nationally representative studies were reported.
      The pragmatic search identified eight countries that changed vaccination schedules from a 1-month interval between the birth dose and the second dose (0-1 months) to a 2-month interval (0-2 months). Three of these countries, Australia, Brunei Darussalam, and Malaysia, changed the schedule when the hexavalent vaccine DTaP-IPV-HepB-Hib was introduced into the national vaccination program. The remaining five countries (Maldives, Marshall Islands, Mongolia, Myanmar, and Vietnam) altered the schedule when a DTwP-HepB-Hib pentavalent vaccine was introduced. The systematic review did not identify any study reporting HBsAg seroprevalence in children born after the change in vaccination schedule from 0-1 to 0-2 months in these countries.

      Discussion

      This review presents a comprehensive overview of the seroprevalence of HBsAg in children in the SEAR and WPR regions over the last 30 years. In the 17 countries with temporal studies or comparisons of different age groups, prevalence of HBV in children tended to decline over time, irrespective of the timing of HBV vaccination programs. A comparison of pre and postvaccine-era cohorts of children, as reported by eight countries, all showed a lower prevalence of HBsAg in the postvaccine-era cohorts than the prevaccine-era cohorts, independent of the HBV vaccination schedule. Similarly, studies assessing change of HBsAg prevalence over time demonstrated a decreasing trend over time, and stratification of children by age or age groups nearly always demonstrated a decrease in younger children. A total of 45 studies reporting HBsAg prevalence in children were identified from China. A clear decrease from high to low prevalence was observed in the included studies; in nationally representative studies, seroprevalence in children aged 1-15 years decreased from 10.4% in 1992 (
      • Xia G
      • Liu C
      • Cao H
      • Bi S
      • Zhan M
      • Su C
      • 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.
      ) to 0.8% in 2014 (
      • 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.
      ).
      It can be assumed that infant vaccination programs have largely driven this decrease in HBV infection; over the time period assessed by this review, estimates of HBV vaccination coverage rates, including that of the birth dose, have increased (
      • UNICEF
      UNICEF Immunization Coverage Data.
      ). These findings imply that the successful implementation of HBV vaccination is key to effectively reducing the HBsAg seroprevalence in children, which should lead to achieving the WHO's global HBV elimination goals by 2030.
      Chronic HBV infection has been largely preventable by vaccination since 1982 (

      World Health Organization. Global hepatitis report. https://www.who.int/publications/i/item/global-hepatitis-report-2017, 2017 (accessed 4 November 2020).

      ). Vaccines currently in use include monovalent, DTaP and DTwP pentavalent, and DTaP hexavalent vaccines; the latter two enable synchronization of the HBV vaccination schedule with the infant vaccination schedule for other childhood diseases. The availability of combination vaccines has led to increased vaccination coverage rates, fewer health care worker visits, and fewer injections required by children to achieve timely immunity to common childhood diseases (
      • Dolhain J
      • Janssens W
      • Dindore V
      • Mihalyi A.
      Infant vaccine co-administration: review of 18 years of experience with GSK's hexavalent vaccine co-administered with routine childhood vaccines.
      ). A study on the integration of the HBV vaccine into the ‘Expanded Programme on Immunization’ in Thailand demonstrated that HBV immunization can be successfully integrated without an adverse effect on coverage rates of other antigens and resulted in a marked reduction in the rate of chronic carriage of HBV in preschool age children (
      • Chunsuttiwat S
      • Biggs BA
      • Maynard J
      • Thamapalo S
      • Laoboripat S
      • Bovornsin S
      • Charanasri U
      • Pinyowiwat W
      • Kunasol P.
      Integration of hepatitis B vaccination into the expanded programme on immunization in Chonburi and Chiangmai provinces, Thailand.
      ).
      Differences between the two WHO regions were apparent. Nationwide immunization was introduced earlier in the WPR, with 21 of 27 countries having a program in place before the year 2000. This region also includes all 10 high-income countries in the study. Countries that do not routinely administer an HBV vaccine birth dose are all in the SEAR. A greater proportion of countries in the SEAR have vaccination coverage rates below 90% for both birth-dose and third-dose HBV vaccination.
      A secondary objective of this review was to explore whether a change in vaccination schedule from an HBV vaccine dose at birth and at 1 month to a schedule of a dose at birth and another at 2 months had any impact on HBsAg seroprevalence in children. Although vaccination schedules in some countries have changed to align with the DTP schedule, this review did not identify any study in those countries that included children born after the schedule change and therefore, no comparison in seroprevalence could be made.
      There is very little published literature comparing HBV vaccination schedules. In a study conducted in infants born from HBsAg-positive mothers of Asian-American ethnicity receiving different types of HBV vaccines with HBIG in different schedules, there was no evidence that the risk of immunoprophylaxis failure was higher with the 0-2 months regimen than with the 0-1 months regimen (odds ratio 0.77, 95% confidence interval 0.39-1.51) (
      • Stevens CE
      • Toy P
      • Kamili S
      • Taylor PE
      • Tong MJ
      • Xia GL
      • Vyas GN.
      Eradicating hepatitis B virus: the critical role of preventing perinatal transmission.
      ). A 2016 WHO systematic review assessed the impact of different intervals between doses on the rate of seroprotection in children. The review did not identify any study specifically comparing the interval between the birth dose and the second dose; however, for other intervals, it did not identify any evidence that different intervals affect the seroprotection rates in children (e.g., 0, 1, and 2 months vs 0, 1, and 6 months). Nevertheless, care must be taken to interpret these results because of a high level of uncertainty owing to the limited number of studies and the high risk of bias in the studies (
      The Cochrane Collaboration
      Optimizing the hepatitis B vaccination schedules. Systematic review of safety and efficacy of childhood schedules using of hepatitis B containing vaccines.
      ).
      The national HBV surveillance in Australia reveals that the prevalence of HBsAg in children has continued to decline since the introduction of HBV vaccination through changes in its schedule from 0, 1, 6 months to 0, 2, 4, 6 months in 2000, and the introduction of a hexavalent DTaP-Hib-HepB-IPV vaccine in 2009 (Supplementary Figure 1).
      HBV MTCT has been defined as HBsAg or viral HepB DNA seropositivity at age 6-12 months in an infant born to an infected mother (
      • Gentile I
      • Borgia G.
      Vertical transmission of hepatitis B virus: challenges and solutions.
      ); although, it is more commonly recommended that this screening is performed no earlier than 9 months to avoid detection of passive antigenemia due to recent vaccination or HBIG (

      Mast E, Margolis H, Fiore A, Brin E, Goldstein S, Wang S, Moyer LA, Bell BP, Alter MJ. A comprehensive immunization strategy to eliminate transmission of hepatitis B virus infection in the United States. https://www.cdc.gov/mmwr/preview/mmwrhtml/rr5416a1.htm, 2005 (accessed 6 June 2022).

      ;
      • Schillie S
      • Murphy TV
      • Fenlon N
      • Ko S
      • Ward JW.
      Update: shortened interval for postvaccination serologic testing of infants born to hepatitis B-infected mothers. Morbiditiy and Mortality Weekly Report.
      ).
      Perinatal MTCT is currently the main mode of HBV transmission worldwide (
      • Gentile I
      • Borgia G.
      Vertical transmission of hepatitis B virus: challenges and solutions.
      ;
      • Mavilia MG
      • Wu GY.
      Mechanisms and prevention of vertical transmission in chronic viral hepatitis.
      ;
      • Nayagam StM
      • Thursz M
      • Sicuri E
      • Conteh L
      • Wiktor S
      • Low-Beer D
      • Hallett T.
      Requirements for global elimination of hepatitis B: a modelling study.
      ). Identification of pregnant women who are HBsAg-positive and risk stratification by HBeAg-positivity or viral HepB DNA levels to determine the women's eligibility for antenatal antiviral prophylaxis is key to further reducing MTCT (
      • Boucheron P
      • Lu Y
      • Yoshida K
      • Zhao T
      • Funk AL
      • Lunel-Fabiani F
      • Guingané A
      • Tuaillon E
      • van Holten J
      • Chou R
      • Bulterys M
      • Shimakawa Y.
      Accuracy of HBeAg to identify pregnant women at risk of transmitting hepatitis B virus to their neonates: a systematic review and meta-analysis.
      ;
      • Funk AL
      • Lu Y
      • Yoshida K
      • Zhao T
      • Boucheron P
      • van Holten J
      • Chou R
      • Bulterys M
      • Shimakawa Y.
      Efficacy and safety of antiviral prophylaxis during pregnancy to prevent mother-to-child transmission of hepatitis B virus: a systematic review and meta-analysis.
      ). Comparison of MTCT rates between countries with different vaccination schedules was not possible due to the low number of studies from countries with 0 and 2-month or 0 and 6-week schedules to compare against those with a 0 and 1-month schedule. High heterogeneity between studies, particularly regarding the vaccination status of children and the use of HBIG in newborns, would also limit any comparison.
      In this review, it was observed that there is a substantial risk of MTCT in children born to mothers who are HBeAg-positive. This indicates the need for additional preventive strategies, such as antenatal antiviral prophylaxis, as recently recommended by the WHO (
      World Health Organization
      Prevention of mother-to-child transmission of hepatitis B virus: guidelines on antiviral prophylaxis in pregnancy.
      ).
      This systematic review has various limitations. The nationally representative studies of HBsAg seroprevalence in children and MTCT were not available for many countries, and wide geographical differences mean that the identified seroprevalence and MTCT rates are not reflective of the entire country. A comparison between pre and postvaccination child HBsAg prevalence in one country might be susceptible to the following confounding factors that could not be adequately addressed in our study: a change in maternal HBsAg prevalence over time, an increase in maternal age at first childbirth, leading to decrease in the risk of MTCT (
      • Moutchia J
      • Njouom R
      • Rumpler E
      • Besombes C
      • Texier G
      • Tejiokem M
      • Crépey P
      • Fontanet A
      • Shimakawa Y.
      Maternal age at first childbirth and geographical variation in HBV prevalence in Cameroon: important role of mother-to-child transmission.
      ), the impact of migrants from countries highly endemic for HBV, and the change in prevalence of HIV infection and the proportion treated with antiretroviral therapy effective against HBV.
      The exclusion of studies where the population was entirely rural or of studies exclusively of tribal or indigenous populations from this review means that HBV seroprevalence may be underestimated for some countries. The prevalence of chronic HBV infection is often higher in these populations than the national average, with higher seroprevalence and lower vaccination coverage rates due to geographical remoteness, lack of access to health care services, and low socioeconomic status.

      Conclusion

      This systematic review examined HBsAg seroprevalence and the risk of MTCT in 38 countries in the SEAR and WPR. We found a decreasing trend in HBsAg seroprevalence in children over time in those studies assessing temporal or age trends, regardless of the vaccination type or schedule used. MTCT of HBV can be effectively prevented by infant immunoprophylaxis; although, the residual higher risk of transmission from mothers who are HBeAg-positive emphasizes the importance of screening to identify high-risk pregnant women who may benefit from antenatal antiviral treatment, as well as their children, who would benefit from receiving neonatal HBIG and HBV vaccine.
      The systematic review did not identify any study allowing us to evaluate whether the risk of HBV infection differs when the second dose after the birth dose was given at the age of 1 month or 2 months. Because of the potential benefits of a combination vaccine synchronized to the DTP schedule to improve vaccination coverage with an efficient use of resources, compared with the historical schedule using monovalent vaccines only at 0, 1, and 6 months, a study directly comparing the risk of HBV infection and the kinetics of the immune response between these two vaccination intervals is highly warranted.
      Countries are encouraged to carry out a comprehensive, prospective collection of HBV seroprevalence data of infants at age 9 months or 2-3 months after completion of vaccination to provide an accurate reflection of the efficacy of HBV vaccination, especially if there has been a change in vaccination schedule. This information can also be used to fine tune the local policy to optimize an HBV eradication program, including incorporation of antiviral treatment for highly viremic women, to achieve the WHO global HBV elimination goals by 2030.

      Funding

      The review was funded by Sanofi. The funder had a role in its design, data interpretation, and drafting the manuscript. All authors had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

      Ethical approval

      Concerning ethical aspects, this study was conducted through a literature review, without subject identification, ensuring individual confidentiality and anonymity.

      Author contributions

      ZM, NP, EV, and JCVZ conceived and designed this study. NP, ZM, and CW performed initial screening, a review of full texts for eligibility and extracted the data. ZM, NP, and CW conducted the data analysis. ZM, NP, JCZV, EV, CW, YS, and KC conducted the data interpretation. ZM and CW drafted the final manuscript and prepared the tables and figures. YS, KC, JCZV, and EV provided critical analysis and made revisions of the manuscript and important intellectual contributions. All authors reviewed the manuscript before final submission.

      Data sharing

      Data is available upon reasonable request to the corresponding author.

      Declaration of competing interests

      KC declares no competing interests. YS received research grants from Gilead Sciences. ZM, NP, and CW received consulting fees from Sanofi. JCVZ and EV are Sanofi employees, a manufacturer, and distributor of many hepatitis B-containing combination vaccines and may hold shares and/or stock options in the company.

      Acknowledgments

      The authors would like to thank Rebecca Harris (Sanofi employee) and Nadia Minarovic (a Sanofi employee at the time of the review) for their assistance with the protocol for the systematic literature review. The authors are grateful to Sheila Harvey (Maverex) for her assistance in conducting the quality assessment.

      References

        • Achwan WA
        • Muttaqin Z
        • Zakaria E
        • Depamede SA
        • Mulyanto SS
        • Tsuda F
        • Takahashi K
        • Abe N
        • Mishiro S.
        Epidemiology of hepatitis B, C, and E viruses and human immunodeficiency virus infections in Tahuna, Sangihe-Talaud archipelago, Indonesia.
        Intervirology. 2007; 50: 408-411
        • Bairwa M
        • Pilania M
        • Rajput M
        • Khanna P
        • Kumar N
        • Nagar M
        • Chawla S.
        Pentavalent vaccine: a major breakthrough in India's Universal Immunization Program.
        Hum Vaccin Immunother. 2012; 8: 1314-1316
        • Bialek SR
        • Helgenberger L
        • Fischer GE
        • Bower WA
        • Konelios M
        • Chaine JP
        • Armstrong G
        • Williams IT
        • Bell BP
        Impact of routine hepatitis B immunization on the prevalence of chronic hepatitis B virus infection in the Marshall Islands and the Federated States of Micronesia.
        Pediatr Infect Dis J. 2010; 29: 18-22
        • Black AP
        • Nouanthong P
        • Nanthavong N
        • Souvannaso C
        • Vilivong K
        • Jutavijittum P
        • Samountry B
        • Lütteke N
        • Hübschen JM
        • Goossens S
        • Quet F
        • Buisson Y
        • Muller CP.
        Hepatitis B virus in the Lao People's Democratic Republic: a cross sectional serosurvey in different cohorts.
        BMC Infect Dis. 2014; 14: 457
        • Boucheron P
        • Lu Y
        • Yoshida K
        • Zhao T
        • Funk AL
        • Lunel-Fabiani F
        • Guingané A
        • Tuaillon E
        • van Holten J
        • Chou R
        • Bulterys M
        • Shimakawa Y.
        Accuracy of HBeAg to identify pregnant women at risk of transmitting hepatitis B virus to their neonates: a systematic review and meta-analysis.
        Lancet Infect Dis. 2021; 21: 85-96
        • Breakwell L
        • Anga J
        • Cooley G
        • Ropiti L
        • Gwyn S
        • Wannemuehler K
        • Woodring J
        • Ogaoga D
        • Martin D
        • Patel M
        • Tohme RA.
        Seroprevalence of chronic hepatitis B virus infection and immunity to measles, rubella, tetanus and diphtheria among schoolchildren aged 6–7 years old in the Solomon Islands, 2016.
        Vaccine. 2020; 38: 4679-4686
        • Burgess MA
        • McIntosh EDG
        • Allars HM
        • Kenrick KG.
        Hepatitis B in urban Australian schoolchildren. No evidence of horizontal transmission between high-risk and low-risk groups.
        Med J Aust. 1993; 159: 315-319
      1. California dental association Foundation Polaris Observatory. Polaris global HBV prevalence estimate for 2016. https://cdafound.org/polaris-regions-dashboard/, 2020 (accessed 4 November 2020).

        • Chen HL
        • Lin LH
        • Hu FC
        • Lee JT
        • Lin WT
        • Yang YJ
        • Huang FC
        • Wu SF
        • Chen SCC
        • Wen WH
        • Chu CH
        • Ni YH
        • Hsu HY
        • Tsai PL
        • Chiang CL
        • Shyu MK
        • Lee PI
        • Chang FY
        • Chang MH.
        Effects of maternal screening and universal immunization to prevent mother-to-infant transmission of HBV.
        Gastroenterology. 2012; 142 (e2): 773-781
        • Chen T
        • Wang J
        • Qiu H
        • Yu Q
        • Yan T
        • Qi C
        • Cao F
        • Tian Z
        • Guo D
        • Yao N
        • Yang Y
        • He Y
        • Zhao Y
        • Liu J.
        Different interventional criteria for chronic hepatitis B pregnant women with HBeAg (+) or HBeAg (-): epidemiological data from Shaanxi.
        China. Medicien (Baltimore). 2018; 97: e11406
        • Cheng JQ
        • Ma HW
        • Xie X
        • Lu Y
        • Zhang YB
        • Dong SX
        • Wang T
        • Liu Y
        • Ling W
        • Hao Y.
        Sero-epidemiological investigation on hepatitis B among permanent residents in Shenzhen area.
        Zhonghua Liu Xing Bing Xue Za Zhi. 2013; 34: 1179-1182
        • Cheung KW
        • Seto MTY
        • Kan ASY
        • Wong D
        • Kou KO
        • So PL
        • Lau WL
        • Jalal K
        • Chee YY
        • Wong RMS
        • Lee CP
        • Ng EHY.
        Immunoprophylaxis failure of infants born to hepatitis B carrier mothers following routine vaccination.
        Clin Gastroenterol Hepatol. 2018; 16: 144-145
        • Choi KC
        • Wong CL
        • Ieong KM.
        Effectiveness of Macau hepatitis B vaccination programme for newborns from hepatitis B carrier mother.
        Hong Kong J Pediatr. 2019; 24: 76-79
        • Chunsuttiwat S
        • Biggs BA
        • Maynard J
        • Thamapalo S
        • Laoboripat S
        • Bovornsin S
        • Charanasri U
        • Pinyowiwat W
        • Kunasol P.
        Integration of hepatitis B vaccination into the expanded programme on immunization in Chonburi and Chiangmai provinces, Thailand.
        Vaccine. 1997; 15: 769-774
        • 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: 765-772
        • Davaalkham D
        • Ojima T
        • Nymadawa P
        • Tsend N
        • Lkhagvasuren T
        • Wiersma S
        • Uehara R
        • Watanabe M
        • Oki I
        • Nakamura Y.
        Seroepidemiology of hepatitis B virus infection among children in Mongolia: results of a nationwide survey.
        Pediatr Int. 2007; 49: 368-374
        • Davaalkham D
        • Ojima T
        • Uehara R
        • Watanabe M
        • Oki I
        • Wiersma S
        • Nymadawa P
        • Nakamura Y.
        Impact of the universal hepatitis B immunization program in Mongolia: achievements and challenges.
        J Epidemiol. 2007; 17: 69-75
        • Ding Y
        • Sheng Q
        • Ma L
        • Dou X.
        Chronic HBV infection among pregnant women and their infants in Shenyang, China.
        Virol J. 2013; 10: 17
        • Dodd D.
        Benefits of combination vaccines: effective vaccination on a simplified schedule.
        Am J Manag Care. 2003; 9: S6-12
        • Dolhain J
        • Janssens W
        • Dindore V
        • Mihalyi A.
        Infant vaccine co-administration: review of 18 years of experience with GSK's hexavalent vaccine co-administered with routine childhood vaccines.
        Expert Rev Vaccines. 2020; 19: 419-443
        • Dong Y
        • Liu SL
        • Zhai XJ
        • Zhu FC
        • Pan H
        • Yu JX
        • Chen YZ
        • Xie YR
        • Zhang XY
        • Zhang HM
        • Li LJ
        • Wang H
        • Ruan B.
        A serological and molecular survey of hepatitis B in children 15 years after inception of the national hepatitis B vaccination program in eastern China.
        J Med Virol. 2009; 81: 1517-1524
        • Du F
        • Liu QL
        • Fu QP
        • Sun L
        • Ao R
        • Guan XJ
        • et al.
        A seroepidemiologic analysis of hepatitis B in Sichuan province.
        Zhonghua Liu Xing Bing Xue Za Zhi. 2009; 30: 139-143
        • Evans AA
        • Cohen C
        • Huang P
        • Qian L
        • London WT
        • Block JM
        • Chen G.
        Prevention of perinatal hepatitis B transmission in Haimen City, China: results of a community public health initiative.
        Vaccine. 2015; 33: 3010-3015
        • Funk AL
        • Lu Y
        • Yoshida K
        • Zhao T
        • Boucheron P
        • van Holten J
        • Chou R
        • Bulterys M
        • Shimakawa Y.
        Efficacy and safety of antiviral prophylaxis during pregnancy to prevent mother-to-child transmission of hepatitis B virus: a systematic review and meta-analysis.
        Lancet Infect Dis. 2021; 21: 70-84
        • Gao P
        • Wang H
        • Chen WX
        • Sun YN
        • Zhang W
        • Pang XH
        • He X
        • Wu J.
        A sero-epidemiological study of hepatitis B among general population in Beijing.
        Zhonghua Liu Xing Bing Xue Za Zhi. 2016; 37: 658-662
        • Gentile I
        • Borgia G.
        Vertical transmission of hepatitis B virus: challenges and solutions.
        Int J Womens Health. 2014; 6: 605-611
        • Gong XH
        • Liu LR
        • Jia L
        • Li YH
        • Xing YL
        • Wang QY.
        [Epidemiological effect of hepatitis B immunization among newborn babies in Beijing].
        Zhonghua Gan Zang Bing Za Zhi. 2003; 11: 201-202
        • Gong XH
        • Wang FZ
        • Li H
        • Liu LR
        • Li YH
        • Wang BL
        • Li LQ
        • Zhang Z
        • Han QY
        • Tang TW.
        Observation on effects of hepatitis B vaccine immunization for 12 years in children in Beijing.
        Zhonghua Yu Fang Yi Xue Za Zhi (Zhonghua Yu Fang Yi Xue Za Zhi). 2005; 39: 265-268
        • Guo Y
        • Liu J
        • Meng L
        • Meina H
        • Du Y.
        Survey of HBsAg-positive pregnant women and their infants regarding measures to prevent maternal-infantile transmission.
        BMC Infect Dis. 2010; 10: 26
        • Hsu HM
        • Lu CF
        • Lee SC
        • Lin SR
        • Chen DS.
        Seroepidemiologic survey for hepatitis B virus infection in Taiwan: the effect of hepatitis B mass immunization.
        J Infect Dis. 1999; 179: 367-370
        • Hu N
        • Xu JN
        • Li F
        • Fu T
        • Wang HR
        • Gao J
        • Zhang L.
        Epidemiology study of intrauterine transmission of HBV in HBsAg-positive parturients in Xi'an.
        Zhonghua Liu Xing Bing Xue Za Zhi. 2019; 40: 1059-1064
        • Huang P
        • Zhu LG
        • Zhu YF
        • Yue M
        • Su J
        • Zhu FC
        • Yang HT
        • Zhang Y
        • Shen HB
        • Yu RB
        • Zhai XJ
        • Peng ZH.
        Seroepidemiology of hepatitis B virus infection and impact of vaccination.
        World J Gastroenterol. 2015; 21: 7842-7850
        • Ji Z
        • Wang T
        • Shao Z
        • Huang D
        • Wang A
        • Guo Z
        • Long Y
        • Zhang L
        • Su H
        • Zhang Q
        • Yan Y
        • Fan D.
        A population-based study examining hepatitis B virus infection and immunization rates in Northwest China.
        PLOS ONE. 2014; 9: e97474
        • Jutavijittum P
        • Jiviriyawat Y
        • Yousukh A
        • Hayashi S
        • Toriyama K.
        Evaluation of a hepatitis B Vaccination Program in Chiang Mai.
        Thailand. Southeast Asian J Trop Med Public Health. 2005; 36: 207-212
        • Kang W
        • Ding Z
        • Shen L
        • Zhao Z
        • Huang G
        • Zhang J
        • Xiong Q
        • Zhang S
        • Zhang S
        • Wang F.
        Risk factors associated with immunoprophylaxis failure against mother to child transmission of hepatitis B virus and hepatitis B vaccination status in Yunnan Province, China.
        Vaccine. 2014; 32: 3362-3366
        • Kang W Y
        • Tian Z
        • Li Q
        • Zhang L
        • Xu L.
        Sero-epidemiological survey on hepatitis B virus in Yunnan Province, between 2006 and 2014.
        Chin J Endemiology. 2017; 38: 518-521
        • Kang W
        • Li Q
        • Shen L
        • Zhang L
        • Tian Z
        • Xu L
        • Qiu F
        • Wang F.
        Risk factors related to the failure of prevention of hepatitis B virus mother-to-child transmission in Yunnan, China.
        Vaccine. 2017; 35: 605-609
        • Khue PM
        • Thi Thuy Linh N
        • Hai Vinh V
        • Vu Dung L
        • Nguyen Van B.
        Hepatitis B Infection and Mother-to-Child Transmission in Haiphong, Vietnam: A Cohort Study with Implications for Interventions.
        Biomed Res Int. 2020; 4747965
        • Kim JH
        • Kim JS
        • Lee JJ
        • Kim JH
        • Kim SY
        • Jung YK
        • Kwon OS
        • Kim YS
        • Choi DJ
        • Kim JH.
        Survey of perinatal hepatitis B virus transmission after Korean National Prevention Program in a tertiary hospital.
        Korean J Intern Med. 2014; 29: 307-314
        • Kitau R
        • Datta SS
        • Patel MK
        • Hennessey K
        • Wannemuehler K
        • Sui G
        • Lagani W.
        Hepatitis B surface antigen seroprevalence among children in Papua New Guinea, 2012–2013.
        Am J Trop Med Hyg. 2015; 92: 501-506
        • Ko K
        • Takahashi K
        • Nagashima S
        • Yamamoto C
        • Ork V
        • Sugiyama A
        • Akita T
        • Ohisa M
        • Chuon C
        • Hossain MS
        • Mao B
        • Tanaka J.
        Existence of hepatitis B virus surface protein mutations and other variants: demand for hepatitis B infection control in Cambodia.
        BMC Infect Dis. 2020; 20: 305
        • Komada K
        • Sugiyama M
        • Vongphrachanh P
        • Xeuatvongsa A
        • Khamphaphongphane B
        • Kitamura T
        • Kiyohara T
        • Wakita T
        • Oshitani H
        • Hachiya M.
        Seroprevalence of chronic hepatitis B, as determined from dried blood spots, among children and their mothers in central Lao People's Democratic Republic: A multistage, stratified cluster sampling survey.
        Int J Infect Dis. 2015; 36: 21-26
        • Latthaphasavang V
        • Vanhems P
        • Ngo-Giang-Huong N
        • Sibounlang P
        • Paboriboune P
        • Malato L
        • Keoluangkhot V
        • Thammasack S
        • Salvadori N
        • Khamduang W
        • Steenkeste N
        • Trépo C
        • Dény P
        • Jourdain G.
        Perinatal hepatitis B virus transmission in Lao PDR: a prospective cohort study.
        PLoS One. 2019; 14e0215011
        • Li F
        • Wang Q
        • Zhang L
        • Su H
        • Zhang J
        • Wang T
        • Huang D
        • Wu J
        • Yan Y
        • Fan D.
        The risk factors of transmission after the implementation of the routine immunization among children exposed to HBV infected mothers in a developing area in northwest China.
        Vaccine. 2012; 30: 7118-7122
        • Li L
        • He J
        • Zhao L.
        Epidemiologic features of viral hepatitis in Fujian.
        Zhonghua Liu Xing Bing Xue Za Zhi. 1998; 19: 89-92
        • Li X
        • Zheng Y
        • Liau A
        • Cai B
        • Ye D
        • Huang F
        • et al.
        Hepatitis B virus infections and risk factors among the general population in Anhui Province, China: an epidemiological study.
        BMC Public Health. 2012; 12: 272
        • Li YC
        • Zhu XJ
        • Zhang ZL.
        [Study on the status of HBV infection and influencing factors in a population aged 1 to 59 years old in Tianjin].
        Zhonghua Liu Xing Bing Xue Za Zhi. 2009; 30: 652
        • Liang X
        • Bi S
        • Yang W
        • Wang L
        • Cui G
        • Cui F
        • et al.
        Epidemiological serosurvey of hepatitis B in China—declining HBV prevalence due to hepatitis B vaccination.
        Vaccine. 2009; 27: 6550-6557
        • 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: 39-47
        • Liang XF
        • Chen YS
        • Wang XJ
        • He X
        • Chen LJ
        • Wang J
        • Lin C
        • Bai H
        • Yan J
        • Cui G
        • Yu J.
        [A study on the sero-epidemiology of hepatitis B in Chinese population aged over 3-years old].
        Zhonghua Liu Xing Bing Xue Za Zhi. 2005; 26: 655-658
        • Liu J
        • Lv J
        • Yan B
        • Feng Y
        • Song L
        • Xu A
        • Zhang L
        • Yan Y.
        Comparison between two population-based hepatitis B serosurveys with an 8-year interval in Shandong Province, China.
        Int J Infect Dis. 2017; 61: 13-19
        • Liu J
        • Xu B
        • Chen T
        • Chen J
        • Feng J
        • Xu C
        • Liu L
        • Hu Y
        • Zhou YH.
        Presence of hepatitis B virus markers in umbilical cord blood: exposure to or infection with the virus?.
        Dig Liver Dis. 2019; 51: 864-869
        • Liu XJ
        • Li WL
        • Peng YY
        • Wang J
        • Ren T
        • Wang LP
        • Yuan P.
        Prevalence of hepatitis B surface antigens and hepatitis B surface antibodies in 1–12 years-old children in Mianyang, Sichuan.
        Sichuan Da Xue Xue Bao Yi Xue Ban. 2018; 49: 304-308
        • Lopez AL
        • Ylade M
        • Daag JV
        • Tandoc AO
        • Bonifacio J
        • Sylim PG
        • Sy AK
        • Centeno R
        • Roque Jr, V
        • Ducusin MJ
        Hepatitis B seroprevalence among 5 to 6 years old children in the Philippines born prior to routine hepatitis B vaccination at birth.
        Hum Vaccin Immunother. 2018; 14: 2491-2496
        • Lu J
        • Li H
        • Tian R
        • Jiang Y
        • Xu Y
        • Yu D
        • Jiang J
        • Bi S.
        Hepatitis viruses infection situation in human population of the Gansu province.
        Zhonghua Shi Yan He Lin Chuang Bing Du Xue Za Zhi. 2009; 23: 349-351
        • Lu J
        • Zhou Y
        • Lin X
        • Jiang Y
        • Tian R
        • Zhang Y
        • Wu J
        • Zhang F
        • Zhang Y
        • Wang Y
        • Bi S.
        General epidemiological parameters of viral hepatitis A, B, C, and E in six regions of China: a cross-sectional study in 2007.
        PLoS One. 2009; 4: e8467
        • Mao B
        • Patel MK
        • Hennessey K
        • Duncan RJ
        • Wannemuehler K
        • Soeung SC.
        Prevalence of chronic hepatitis B virus infection after implementation of a hepatitis B vaccination program among children in three provinces in Cambodia.
        Vaccine. 2013; 31: 4459-4464
      2. Mast E, Margolis H, Fiore A, Brin E, Goldstein S, Wang S, Moyer LA, Bell BP, Alter MJ. A comprehensive immunization strategy to eliminate transmission of hepatitis B virus infection in the United States. https://www.cdc.gov/mmwr/preview/mmwrhtml/rr5416a1.htm, 2005 (accessed 6 June 2022).

        • Mavilia MG
        • Wu GY.
        Mechanisms and prevention of vertical transmission in chronic viral hepatitis.
        J Clin Transl Hepatol. 2017; 5: 119-129
        • Moher D
        • Liberati A
        • Tetzlaff J
        • Altman DG
        • Group PRISMA
        Preferred Reporting Items for Systematic Reviews and Meta-Analyses: the PRISMA statement.
        Ann Intern Med. 2009; 151: 264-269
        • Moutchia J
        • Njouom R
        • Rumpler E
        • Besombes C
        • Texier G
        • Tejiokem M
        • Crépey P
        • Fontanet A
        • Shimakawa Y.
        Maternal age at first childbirth and geographical variation in HBV prevalence in Cameroon: important role of mother-to-child transmission.
        Clin Infect Dis. 2022; 74: 836-845
        • Murhekar MV
        • Santhosh Kumar M
        • Kamaraj P
        • Khan SA
        • Allam RR
        • Barde P
        • Dwibedi B
        • Kanungo S
        • Mohan U
        • Mohanty SS
        • Roy S
        • Sagar V
        • Savargaonkar D
        • Tandale BV
        • Topno RK
        • Kumar CPG
        • Sabarinathan R
        • Bitragunta S
        • Grover GS
        • Lakshmi PVM
        • Mishra CM
        • Sadhukhan P
        • Sahoo PK
        • Singh SK
        • Yadav CP
        • Kumar R
        • Dutta S
        • Toteja GS
        • Gupta N
        • Mehendale SM
        ICMR – Serosurvey group. Hepatitis-B virus infection in India: findings from a nationally representative serosurvey, 2017–18.
        Int J Infect Dis. 2020; 100: 455-460
        • Nayagam StM
        • Thursz M
        • Sicuri E
        • Conteh L
        • Wiktor S
        • Low-Beer D
        • Hallett T.
        Requirements for global elimination of hepatitis B: a modelling study.
        Lancet Infect Dis. 2016; 16: 1399-1408
        • Ng KP
        • Saw TL
        • Baki A
        • Rozainah K
        • Pang KW
        • Ramanathan M.
        Impact of the Expanded Program of Immunization against hepatitis B infection in school children in Malaysia.
        Med Microbiol Immunol. 2005; 194: 163-168
        • Nguyen TH
        • Vu MH
        • Nguyen VC
        • Nguyen LH
        • Toda K
        • Nguyen TN
        • Dao S
        • Wannemuehler KA
        • Hennessey KA.
        A reduction in chronic hepatitis B virus infection prevalence among children in Vietnam demonstrates the importance of vaccination.
        Vaccine. 2014; 32: 217-222
        • Noto H
        • Terao T
        • Ryou S
        • Hirose Y
        • Yoshida T
        • Ookubo H
        • Mito H
        • Yoshizawa H
        Special Committee for Preventing Hepatitis B in Shizuoka. Combined passive and active immunoprophylaxis for preventing perinatal transmission of the hepatitis B virus carrier state in Shizuoka, Japan during 1980–1994.
        J Gastroenterol Hepatol. 2003; 18: 943-949
        • O'Sullivan BG
        • Gidding HF
        • Law M
        • Kaldor JM
        • Gilbert GL
        • Dore GJ.
        Estimates of chronic hepatitis B virus infection in Australia, 2000.
        Aust N Z J Public Health. 2004; 28: 212-216
        • Ochirbat T
        • Ali M
        • Pagbajab N
        • Erkhembaatar LO
        • Budbazar E
        • Sainkhuu N
        • Tudevdorj E
        • Kuroiwa C.
        Assessment of hepatitis B vaccine-induced seroprotection among children 5–10 years old in Ulaanbaatar, Mongolia.
        BioSci Trends. 2008; 2: 68-74
        • Ork V
        • Woodring J
        • Md Shafiqul Hossain
        • Wasley A
        • Nagashima S
        • Yamamoto C
        • Chuon C
        • Sugiyama A
        • Ohisa M
        • Akita T
        • Ko K
        • Mao B
        • Tanaka J
        Hepatitis B surface antigen seroprevalence among pre- and post-vaccine cohorts in Cambodia, 2017.
        Vaccine. 2019; 37: 5059-5066
        • Patel MK
        • Wannemuehler K
        • Tairi R
        • Tutai R
        • Moturi E
        • Tabwaia B
        • Nikuata AB
        • Etuale MF
        • Mokoia G.
        Progress towards achieving hepatitis B control in the Cook Islands, Niue, Tokelau, and Kiribati.
        Vaccine. 2016; 34: 4298-4303
        • Paul RC
        • Rahman M
        • Wiesen E
        • Patel M
        • Banik KC
        • Sharif AR
        • Sultana S
        • Rahman M
        • Liyanage J
        • Abeysinghe N
        • Kamili S
        • Murphy T
        • Luby SP
        • Mast EE.
        Hepatitis B surface antigen seroprevalence among prevaccine and vaccine era children in Bangladesh.
        Am J Trop Med Hyg. 2018; 99: 764-771
        • 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: 51-57
        • Peng TT
        • Cai QE
        • Yang M
        • Chen SP
        • Chen F
        • Wang M
        • Peng L
        • Wong G
        • Shen CG
        • Cheng WB
        • Liu SY
        • Peng YB
        • Peng JH
        • Chen CM
        • Yang LQ
        • Tang YM
        • Xu ZX
        • Liu YX.
        Epidemiological trends and virological traits of hepatitis B virus infection in pregnant women and neonates.
        Arch Virol. 2019; 164: 1335-1341
        • Posuwan N
        • Wanlapakorn N
        • Sa-Nguanmoo P
        • Wasitthankasem R
        • Vichaiwattana P
        • Klinfueng S
        • Vuthitanachot V
        • Sae-Lao S
        • Foonoi M
        • Fakthongyoo A
        • Makaroon J
        • Srisingh K
        • Asawarachun D
        • Owatanapanich S
        • Wutthiratkowit N
        • Tohtubtiang K
        • Yoocharoen P
        • Vongpunsawad S
        • Poovorawan Y.
        The success of a universal hepatitis B immunization program as part of Thailand's EPI after 22 years’ implementation.
        PLOS ONE. 2016; 11e0150499
        • Purwono PB
        • Juniastuti Amin M
        • Bramanthi R
        • Nursidah Resi EM
        • Wahyuni RM
        • Yano Y
        • Soetjipto Hotta H
        • Hayashi Y
        • Utsumi T
        • Lusida MI
        Hepatitis B virus infection in Indonesia 15 years after adoption of a universal infant vaccination program: possible impacts of low birth dose coverage and a vaccine-escape mutant.
        Am J Trop Med Hyg. 2016; 95: 674-679
        • Qiao YP
        • Su M
        • Song Y
        • Wang XY
        • Li Z
        • Li YL
        • Dou LX
        • Wang Q
        • Hann K
        • Zhang GM
        • Huang XN
        • Yang YN
        • Jin X
        • Wang AL
        Outcomes of the national programme on prevention of mother-to-child transmission of hepatitis B virus in China, 2016–2017.
        Infect Dis Poverty. 2019; 8: 65
        • Sasagawa Y
        • Yamada H
        • Morizane M
        • Deguchi M
        • Shirakawa T
        • Morioka I
        • Tanimura K.
        Hepatitis B virus infection: prevention of mother-to-child transmission and exacerbation during pregnancy.
        J Infect Chemother. 2019; 25: 621-625
        • Schillie S
        • Murphy TV
        • Fenlon N
        • Ko S
        • Ward JW.
        Update: shortened interval for postvaccination serologic testing of infants born to hepatitis B-infected mothers. Morbiditiy and Mortality Weekly Report.
        MMWR Morb Mortal Wkly Rep. 2015; 64: 1118-1120
        • Shao X
        • Wu C
        • Wang F
        • Liang J
        • Xie X
        • Zhu Q
        • Liu J
        • Hu P
        • Qiu Q
        • Liang X
        • Zheng H.
        Seroepidemiological analysis of hepatitis B among children aged 1–14 in 3 counties of Guangdong Province in 2013.
        Zhonghua Yu Fang Yi Xue Za Zhi. 2015; 49: 777-781
        • Shao ZJ
        • Zhang L
        • Xu JQ
        • Xu DZ
        • Men K
        • Zhang JX
        • Cui HC
        • Yan YP.
        Mother-to-infant transmission of hepatitis B virus: a Chinese experience.
        J Med Virol. 2011; 83: 791-795
        • Shirakawa T
        • Sasagawa Y
        • Deguchi M
        • Tanimura K
        • Morizane M
        • Morioka I
        • et al.
        Efficacy of maternal screening and perinatal prevention program for hepatitis B.
        J Obstet Gynaecol Res. 2018; 44: 1529-1530
        • Soeung SC
        • Rani M
        • Huong V
        • Sarath S
        • Kimly C
        • Kohei T
        Results from nationwide hepatitis B serosurvey in Cambodia using simple and rapid laboratory test: implications for national immunization program.
        Am J Trop Med Hyg. 2009; 81: 252-257
        • Stevens CE
        • Toy P
        • Kamili S
        • Taylor PE
        • Tong MJ
        • Xia GL
        • Vyas GN.
        Eradicating hepatitis B virus: the critical role of preventing perinatal transmission.
        Biologicals. 2017; 50: 3-19
        • Su H
        • Shao Z
        • Pu Z
        • Wang Y
        • Zhang L
        • Zhang W
        • Wang B
        • Wang A
        • Ji Z
        • Yan Y
        • Zhang Y
        Overt and occult hepatitis B virus infection among community children in Northwest China.
        J Viral Hepat. 2017; 24: 797-803
        • Su H
        • Zhang Y
        • Xu D
        • Wang B
        • Zhang L
        • Li D
        • Xiao D
        • Li F
        • Zhang J
        • Yan Y
        Occult hepatitis B virus infection in anti-HBs-positive infants born to HBsAg-positive mothers in China.
        PLOS ONE. 2013; 8: e70768
        • Sugiyama A
        • Ohisa M
        • Nagashima S
        • Yamamoto C
        • Chuon C
        • Fujii T
        • et al.
        Reduced prevalence of hepatitis B surface antigen positivity among pregnant women born after the national implementation of immunoprophylaxis for babies born to hepatitis B virus-carrier mothers in Japan.
        Hepatol Res. 2017; 14: 1329-1334
        • Tanaka J
        • Woodring JV
        • Ork V
        • Bunsoth M
        • Nagashima S
        • Yamamoto C
        • Choun C
        • Ko K
        • Hossain S.
        Sero-prevalence of hepatitis B surface antigen among 5–7 years old children and their mothers in Cambodia by nationwide multistage stratified random sampling strategy.
        J Hepatol. 2018; 68: S167-S168
        • Tao Y
        • Yan L
        • Wang C
        • Xu H
        • Zhang J
        • Yu JX.
        Seroprevalence of hepatitis B in populations at ages of 1–59 years in Changchun City, Jilin Province, China in 2006 and 2016.
        Chin J Biol. 2018; 31: 1114-1117
        • The Cochrane Collaboration
        Optimizing the hepatitis B vaccination schedules. Systematic review of safety and efficacy of childhood schedules using of hepatitis B containing vaccines.
        The Cochrane Collaboration, London2016
        • Tse K
        • Siu SLY
        • Yip KT
        • Chan SM
        • Que TL
        • Lui WYS
        • Chan PS.
        Immuno-prophylaxis of babies borne to hepatitis B carrier mothers.
        Hong Kong Med J. 2006; 12: 368-374
        • Tshering N
        • Dhakal GP
        • Wangchuk U
        • Wangdi S
        • Khandu L
        • Pelden S
        • Nogareda F
        • Patel MK
        • Hutin YJF
        • Wannemuehler K
        • Rewari BB
        • Wangchuk S.
        Prevalence of HBV and HCV infections, Bhutan, 2017: progress and next steps.
        BMC Infect Dis. 2020; 20: 485
        • UNICEF
        UNICEF Immunization Coverage Data.
        https://data.unicef.org/resources/dataset/immunization/
        Date: 2020
        Date accessed: November 4, 2020
        • Upreti SR
        • Gurung S
        • Patel M
        • Dixit SM
        • Krause LK
        • Shakya G
        • Wannemuehler K
        • Rajbhandari R
        • Bohara R
        • William Schluter W.
        Prevalence of chronic hepatitis B virus infection before and after implementation of a hepatitis B vaccination program among children in Nepal.
        Vaccine. 2014; 32: 4304-4309
        • Vranckx R
        • Alisjahbana A
        • Meheus A.
        Hepatitis B virus vaccination and antenatal transmission of HBV markers to neonates.
        J Viral Hepat. 1999; 6: 135-139
        • Wang F
        • Zhang G
        • Zheng H
        • Miao N
        • Shen L
        • Wang F
        Post-vaccination serologic testing of infants born to hepatitis B surface antigen positive mothers in 4 provinces of China.
        Vaccine. 2017; 35: 4229-4235
        • Wang F
        • Zheng H
        • Zhang G
        • Ding Z
        • Li F
        • Zhong G
        • Chen Y
        • Jia Y
        • Miao N
        • Wu Z
        • Sun X
        • Li L
        • Liang X
        • Cui F.
        Effectiveness of prevention of mother-to-child transmission practice in three provinces of Southern China.
        Hum Vaccin Immunother. 2015; 11: 2061-2067
        • Wang FZ
        • Zhang GM
        • Shen LP
        • Zheng H
        • Wang F
        • Miao N
        • Yuan QL
        • Sun XJ
        • Bi SL
        • Liang XF
        • Wang HQ.
        [Comparative analyze on hepatitis B seroepidemiological surveys among population aged 1–29 years in different epidemic regions of China in 1992 and 2014].
        Zhonghua Yu Fang Yi Xue Za Zhi. 2017; 51: 462-468
        • Wang FZ
        • Zhang GM
        • Shen LP
        • Liu JH
        • Zheng H
        • Wang F
        • Miao N
        • Sun XJ
        • Liang XF
        • Cui FQ.
        Epidemiological characteristics of children aged 1–4 years without timely birth dose of hepatitis B vaccine vaccination in China, 2014.
        Zhonghua Liu Xing Bing Xue Za Zhi. 2017; 38: 32-36
        • Wang FZ
        • Zheng H
        • Miao N
        • Sun XJ
        • Zhang GM
        • Liang XF
        • Cui FQ.
        [Analysis on sero-epidemiological characteristics of hepatitis B virus among people born during 1994–2001 before and after hepatitis B vaccine catch-up vaccination, China].
        Zhonghua Yu Fang Yi Xue Za Zhi (Zhonghua Yu Fang Yi Xue Za Zhi). 2017; 51: 469-474
        • Wang F
        • Kang W
        • Zhou W
        • Su Q
        • Bi S
        • Qiu F
        • Li Q.
        Investigation of the risk factors associated with the failure of hepatitis B vaccination of neonates in Yunnan Province, China.
        Int J Infect Dis. 2018; 77: 90-95
        • Wang H
        • Zhang W
        • Ma JX
        • Li LQ
        • Zhang XC
        • Li SM
        • Wu K
        • Li Q
        • Liu X
        • Pang X.
        [Survey on seroepidemiological status and vaccine coverage of hepatitis B among children in Chaoyang district of Beijing in 2010].
        Zhonghua Yu Fang Yi Xue Za Zhi (Zhonghua Yu Fang Yi Xue Za Zhi). 2013; 47: 223-226
        • Wang S
        • Tao Y
        • Tao Y
        • Jiang J
        • Yan L
        • Wang C
        • Ding Y
        • Yu J
        • Zhao D
        • Chi X
        • Wang X
        • Wu R
        • Gao X
        • Shi Y
        • Guan Y
        • Li Y
        • Xing Y
        • Sun H
        • Ta C
        • Wang C
        • Niu J
        • Meng J
        • Xu H
        Epidemiological study of hepatitis B and hepatitis C infections in northeastern China and the beneficial effect of the vaccination strategy for hepatitis B: a cross-sectional study.
        BMC Public Health. 2018; 18: 1088
        • Wang X
        • Ding D
        • Sun B.
        [Epidemiological feature of hepatitis B in Zaozhuang City, Shandong Province].
        Zhonghua Shi Yan He Lin Chuang Bing Du Xue Za Zhi. 2002; 16: 267-269
        • Wang Z
        • Zhang J
        • Yang H
        • Li X
        • Wen S
        • Guo Y
        • Sun J
        • Hou J.
        Quantitative analysis of HBV DNA level and HBeAg titer in hepatitis B surface antigen positive mothers and their babies: HBeAg passage through the placenta and the rate of decay in babies.
        J Med Virol. 2003; 71: 360-366
        • Wells G
        • Shea B
        • O'Connell D
        • Peterson J
        The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses.
        Hum Reprod. 2013; 28: 1943-1952
        • Wilson N
        • Ruff TA
        • Rana BJ
        • Leydon J
        • Locarnini S.
        The effectiveness of the infant hepatitis B immunisation program in Fiji, Kiribati, Tonga and Vanuatu.
        Vaccine. 2000; 18: 3059-3066
        • 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: 489-492
      3. World Health Organization. WHO hepatitis B fact sheet. https://www.who.int/news-room/fact-sheets/detail/hepatitis-b, 2021 (accessed 1 November 2020).

      4. World Health Organization. Global hepatitis report. https://www.who.int/publications/i/item/global-hepatitis-report-2017, 2017 (accessed 4 November 2020).

        • World Health Organization
        Global health sector strategy on viral hepatitis 2016–2021.
        World Health Organization, Geneva2016
        • World Health Organization
        Prevention of mother-to-child transmission of hepatitis B virus: guidelines on antiviral prophylaxis in pregnancy.
        World Health Organization, Geneva2020
        • Wu J
        • Zhang W
        • Han L
        • Lin C
        • Lin H
        • Xing Y
        • Gao P
        • Gong X
        • Liu L
        • Huang F
        • Liu J
        • Liu L
        • Wang H
        • Yu H
        • Liu X
        • Tang Y
        • Pu Y
        • Zhao W
        • Wang C
        • Zhang Z
        • Ma L.
        A sero-epidemiologiecal study on hepatitis B among general population in Beijing.
        Zhonghua Liu Xing Bing Xue Za Zhi. 2007; 28: 555-557
        • Wu JN
        • Wen XZ
        • Zhou Y
        • Lin D
        • Zhang SY
        • Yan YS.
        Impact of the free-vaccine policy on timely initiation and completion of hepatitis B vaccination in Fujian.
        China. J Viral Hepat. 2015; 22: 551-560
        • Xeuatvongsa A
        • Komada K
        • Kitamura T
        • Vongphrachanh P
        • Pathammavong C
        • Phounphenghak K
        • Sisouk T
        • Phonekeo D
        • Sengkeopaseuth B
        • Som-Oulay V
        • Ishii K
        • Wakita T
        • Sugiyama M
        • Hachiya M.
        Chronic hepatitis B prevalence among children and mothers: results from a nationwide, population-based survey in Lao People's Democratic Republic.
        PLoS One. 2014; 9: e88829
        • Xi NN
        • Zuo ZL
        • Long SS
        • Ma YJ
        • Zhang JY.
        A cross-sectional study of hepatitis B virus infection in Mianyang, Sichuan Province.
        Sichuan Da Xue Xue Bao Yi Xue Ban. 2017; 48: 101-106
        • Xia G
        • Liu C
        • Cao H
        • Bi S
        • Zhan M
        • Su C
        • 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: 62-73
        • Xiao J
        • Zhang J
        • Wu C
        • Shao X
        • Peng G
        • Peng Z
        • Ma W
        • Zhang Y
        • Zheng H.
        Impact of hepatitis B vaccination among children in Guangdong Province, China.
        Int J Infect Dis. 2012; 16: e692-e696
        • Yin X
        • Han G
        • Zhang H
        • Wang M
        • Zhang W
        • Gao Y
        • et al.
        A real world, prospective cohort study on mother-to-child transmission of HBV in China (Shield 01).
        Hepatol Int. 2019; S20
        • Yin Y
        • Wu L
        • Zhang J
        • Zhou J
        • Zhang P
        • Hou H.
        Identification of risk factors associated with immunoprophylaxis failure to prevent the vertical transmission of hepatitis B virus.
        J Infect. 2013; 66: 447-452
        • Yonghao G
        • Jin X
        • Jun L
        • Pumei D
        • Ying Y
        • Xiuhong F
        • Yanyang Z
        • Wanshen G
        An epidemiological serosurvey of hepatitis B virus shows evidence of declining prevalence due to hepatitis B vaccination in central China.
        Int J Infect Dis. 2015; 40: 75-80
        • Yonghao G
        • Pumei D
        • Jianhui Y
        • Jin X
        • Yanyang Z
        • Zhe W
        A retrospective study of hepatitis B mother-to-child transmission prevention and postvaccination serological test results of infants at risk of perinatal transmission in two counties of middle China.
        J Viral Hepat. 2017; 24: 687-695
        • Zampino R
        • Boemio A
        • Sagnelli C
        • Alessio L
        • Adinolfi LE
        • Sagnelli E
        • Coppola N.
        Hepatitis B virus burden in developing countries.
        World J Gastroenterol. 2015; 21: 11941-11953
        • Zeng F
        • Guo P
        • Huang Y
        • Xin W
        • Du Z
        • Zhu S
        • Deng Y
        • Zhang D
        • Hao Y.
        Epidemiology of hepatitis B virus infection: results from a community-based study of 0.15 million residents in South China.
        Sci Rep. 2016; 6: 36186
        • Zhai RF
        • Guang M
        • Chang SY
        • An JH
        • Li TS
        • Zhao FM
        • Wang HJ
        • Li H
        • Wang XF.
        Serological survey on viral hepatitis B in the population of Shanxi province.
        Zhonghua Liu Xing Bing Xue Za Zhi. 2010; 31: 479-480
        • Zhang L
        • Gui X
        • Fan J
        • Wang B
        • Ji H
        • Yisilafu R
        • Li F
        • Zhou Y
        • Tong Y
        • Kong X
        • Ye P
        • Zong L
        Breast feeding and immunoprophylaxis efficacy of mother-to-child transmission of hepatitis B virus.
        J Matern Fetal Neonatal Med. 2014; 27: 182-186
        • Zhang L
        • Gui XE
        • Teter C
        • Zhong H
        • Pang Z
        • Ding L
        • Li F
        • Zhou Y
        • Zhang L.
        Effects of hepatitis B immunization on prevention of mother-to-infant transmission of hepatitis B virus and on the immune response of infants towards hepatitis B vaccine.
        Vaccine. 2014; 32: 6091-6097
        • Zhang L
        • Gui X
        • Wang B
        • Ji H
        • Yisilafu R
        • Li F
        • et al.
        A study of immunoprophylaxis failure and risk factors of hepatitis B virus mother-to-infant transmission.
        Eur J Pediatr. 2014; 173: 1161-1168
        • Zhang L
        • Gui XE
        • Wang B
        • Fan JY
        • Cao Q
        • Mullane K
        • Liang XL.
        Serological positive markers of hepatitis B virus in femoral venous blood or umbilical cord blood should not be evidence of in-utero infection among neonates.
        BMC Infect Dis. 2016; 16: 408
        • Zhang S
        • Li RT
        • Wang Y
        • Liu Q
        • Zhou YH
        • Hu Y.
        Seroprevalence of hepatitis B surface antigen among pregnant women in Jiangsu, China, 17 years after introduction of hepatitis B vaccine.
        Int J Gynaecol Obstet. 2010; 109: 194-197
        • Zhang T
        • Xiao Z
        • Ling H
        • Ge C
        • Ying L
        • Ding Q
        • Kai-Ling X
        • Yan-Ming M
        • Yue-He D
        • Ling-Yang Z
        A community-based sero-epidemiological study of hepatitis B infection in Lianyungang, China, 2010.
        West Pac Surveill Resp. 2012; 3: 69-75
        • Zhang XC
        • Pang XH
        • Zhang W
        • Han LL
        • Lin CY
        • Ma JX
        • Wu K
        • Li SM
        • Wang Q
        • Li L
        • Wang H
        • Gao P.
        [Prevalence of hepatitis B in Chaoyang district, Beijing in 2010].
        Zhonghua Yu Fang Yi Xue Za Zhi (Zhonghua Yu Fang Yi Xue Za Zhi). 2012; 46: 623-626
        • Zhang XH
        • Wang Q
        • Zheng W
        • Li XH
        • Jiang QQ
        • Zhou CF
        • Qiu LQ.
        [Early physical growth and disease analysis among children born delivered by HBsAg-positive mothers].
        Zhonghua Yu Fang Yi Xue Za Zhi (Zhonghua Yu Fang Yi Xue Za Zhi). 2017; 51: 496-500
        • Zhuo J
        • Tao G
        • Ebrahim SH
        • Wang S
        • Luo Z
        • Wang H.
        The relationship of hepatitis B virus infection between adults and their children in Guangxi Province.
        China. J Hepatol. 2000; 33: 628-631
        • Zhang ZB
        • Xue ZX
        • Han ZG
        • Yang QY
        • Zheng QY
        • Zulipikaer T
        • et al.
        Status of seroepidemiology of hepatitis A, B and C in primary and middle school students in Shufu county, Xinjiang Uygur Autonomous Region of China.
        Zhonghua Liu Xing Bing Xue Za Zhi. 2016; 37: 1592-1595
        • Zhou LH
        • Li XQ
        • Ye DQ
        • Zheng YJ
        • Ge FY
        • Cai B
        • Huang F.
        A cross-sectional survey on hepatitis B among general population in areas along Yangzi River in Anhui Province.
        Zhonghua Liu Xing Bing Xue Za Zhi. 2009; 30: 144-146
        • Zhou Y
        • He H
        • Deng X
        • Yan R
        • Tang X
        • Xie S
        • Yao J.
        Significant reduction in notification and seroprevalence rates of hepatitis B virus infection among the population of Zhejiang Province, China, aged between 1 and 29 years from 2006 to 2014.
        Vaccine. 2017; 35: 4355-4361