Hepatitis B virus (HBV) is a global public health concern, and China continues to face a high burden of HBV cases. Vaccination plays a critical role in controlling and eradicating HBV. However, studies have shown that some individuals may experience waning immunity over time, highlighting the importance of enhanced immunization strategies. This study aimed to investigate the relationship between age, gender, and anti-HBs antibody levels, as well as the prevalence of serum hepatitis B surface antigen (HBsAg)/HBV e antigen (HBeAg) positivity. This retrospective study included 43,609 pediatric patients who visited the outpatient department between January 2013 and December 2022. Serum biomarkers (HBsAg, anti-HBs, HBeAg, anti-HBe, and anti-HBc) were measured using Roche Cobas 8000. There is a significant difference in anti-HBs titer between genders and across different age groups (p < 0.05). The serological markers HBsAg/HBeAg exhibited the highest positivity rate in the age group of 15–18 years. The findings demonstrate a gradual decrease in anti-HBs levels following HBV vaccination. The prevalence of serum markers HBsAg/HBeAg is higher among adolescents aged 15–18 years, which should be a matter of concern and attention.
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References
1.
AghakhaniA, BanifazlM, IzadsiN, et al.Persistence of antibody to hepatitis B surface antigen among vaccinated children in a low hepatitis B virus endemic area. World J Pediatr, 2011; 7(4):358–360; doi: 10.1007/s12519-011-0286-4
2.
BauerT, JilgW. Hepatitis B surface antigen-specific T and B cell memory in individuals who had lost protective antibodies after hepatitis B vaccination. Vaccine, 2006; 24(5):572–577; doi: 10.1016/j.vaccine.2005.08.058
3.
BeranJ, Van Der MeerenO, LeyssenM, et al.Immunity to hepatitis A and B persists for at least 15 years after immunisation of adolescents with a combined hepatitis A and B vaccine. Vaccine, 2016; 34(24):2686–2691; doi: 10.1016/j.vaccine.2016.04.033
4.
BruceMG, BrudenD, HurlburtD, et al.Antibody levels and protection after hepatitis B vaccine: Results of a 30-year follow-up study and response to a booster dose. J Infect Dis, 2016; 214(1):16–22; doi: 10.1093/infdis/jiv748
5.
Brunskole HummelI, HuberB, WenzelJJ, et al.Markers of protection in children and adolescents six to fourteen years after primary hepatitis B vaccination in real life: A pilot study. Pediatr Infect Dis J, 2016; 35(3):286–291; doi: 10.1097/inf.0000000000000994
6.
CuiF, WoodringJ, ChanP, et al.Considerations of antiviral treatment to interrupt mother-to-child transmission of hepatitis B virus in China. Int J Epidemiol, 2018; 47(5):1529–1537; doi: 10.1093/ije/dyy077
7.
Dabrowska-LeonikN, Sawicka-PowierzaJ, BernatowskaE, et al.Lack of relationship between 25-hydoxyvitamin D concentration and a titer of antibodies to hepatitis B surface antigen in children under 12 years of age. PLoS One, 2022; 17(11):e0277473; doi: 10.1371/journal.pone.0277473
8.
DoiH, KantoT. Factors influencing the durability of hepatitis B vaccine responses. Vaccine, 2021; 39(36):5224–5230; doi: 10.1016/j.vaccine.2021.07.017
9.
FischingerS, BoudreauCM, ButlerAL, et al.Sex differences in vaccine-induced humoral immunity. Semin Immunopathol, 2019; 41(2):239–249; doi: 10.1007/s00281-018-0726-5
10.
FloreaniA, BaldoV, CristofolettiM, et al.Long-term persistence of anti-HBs after vaccination against HBV: An 18 year experience in health care workers. Vaccine, 2004; 22(5–6):607–610; doi: 10.1016/j.vaccine.2003.09.001
11.
Giefing-KröllC, BergerP, LepperdingerG, et al.How sex and age affect immune responses, susceptibility to infections, and response to vaccination. Aging Cell, 2015; 14(3):309–321; doi: 10.1111/acel.12326
12.
HadziyannisSJ. Natural history of chronic hepatitis B in Euro-Mediterranean and African countries. J Hepatol, 2011; 55(1):183–191; doi: 10.1016/j.jhep.2010.12.030
13.
HammittLL, HennessyTW, FioreAE, et al.Hepatitis B immunity in children vaccinated with recombinant hepatitis B vaccine beginning at birth: A follow-up study at 15 years. Vaccine, 2007; 25(39–40):6958–6964; doi: 10.1016/j.vaccine.2007.06.059
14.
HouJ, CuiF, DingY, et al.Management algorithm for interrupting mother-to-child transmission of hepatitis B virus. Clin Gastroenterol Hepatol, 2019; 17(10):1929–1936.e1921; doi: 10.1016/j.cgh.2018.10.007
15.
HuduSA, HarmalNS, SaeedMI, et al.Naturally occurring hepatitis B virus surface antigen mutant variants in Malaysian blood donors and vaccinees. Eur J Clin Microbiol Infect Dis, 2015; 34(7):1349–1359; doi: 10.1007/s10096-015-2358-1
16.
JanCF, HuangKC, ChienYC, et al.Determination of immune memory to hepatitis B vaccination through early booster response in college students. Hepatology, 2010; 51(5):1547–1554; doi: 10.1002/hep.23543
17.
JingW, LiuJ, LiuM. Eliminating mother-to-child transmission of HBV: Progress and challenges in China. Front Med, 2020; 14(1):21–29; doi: 10.1007/s11684-020-0744-2
18.
JourdainG, Ngo-Giang-HuongN, HarrisonL, et al.Tenofovir versus placebo to prevent perinatal transmission of hepatitis B. N Engl J Med, 2018; 378(10):911–923; doi: 10.1056/NEJMoa1708131
19.
KaneMA, HadlerSC, LeeL, et al.The inception, achievements, and implications of the China GAVI Alliance Project on Hepatitis B Immunization. Vaccine, 2013; 31Suppl 9:J15–J20; doi: 10.1016/j.vaccine.2013.03.045
20.
KimMJ, NafzigerAN, HarroCD, et al.Revaccination of healthy nonresponders with hepatitis B vaccine and prediction of seroprotection response. Vaccine, 2003; 21(11–12):1174–1179; doi: 10.1016/s0264-410x(02)00626-6
21.
KleinSL, MarriottI, FishEN. Sex-based differences in immune function and responses to vaccination. Trans R Soc Trop Med Hyg, 2015; 109(1):9–15; doi: 10.1093/trstmh/tru167
22.
KlingerG, ChodickG, LevyI. Long-term immunity to hepatitis B following vaccination in infancy: Real-world data analysis. Vaccine, 2018; 36(17):2288–2292; doi: 10.1016/j.vaccine.2018.03.028
23.
KosinskaAD, Pishraft-SabetL, WuW, et al.Low hepatitis B virus-specific T-cell response in males correlates with high regulatory T-cell numbers in murine models. Hepatology, 2017; 66(1):69–83; doi: 10.1002/hep.29155
24.
LiM, ZhaoY, ChenX, et al.Contribution of sex-based immunological differences to the enhanced immune response in female mice following vaccination with hepatitis B vaccine. Mol Med Rep, 2019; 20(1):103–110; doi: 10.3892/mmr.2019.10231
25.
LinX, GuoY, ZhouA, et al.Immunoprophylaxis failure against vertical transmission of hepatitis B virus in the Chinese population: A hospital-based study and a meta-analysis. Pediatr Infect Dis J, 2014; 33(9):897–903; doi: 10.1097/inf.0000000000000315
26.
LiuF, GuoZ, DongC. Influences of obesity on the immunogenicity of Hepatitis B vaccine. Hum Vaccin Immunother, 2017; 13(5):1014–1017; doi: 10.1080/21645515.2016.1274475
27.
LiuJ, LiangW, JingW, et al.Countdown to 2030: Eliminating hepatitis B disease, China. Bull World Health Organ, 2019; 97(3):230–238; doi: 10.2471/blt.18.219469
28.
Liver EAftSot. EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection. J Hepatol, 2017; 67(2):370–398; doi: 10.1016/j.jhep.2017.03.021
29.
LuCY, NiYH, ChiangBL, et al.Humoral and cellular immune responses to a hepatitis B vaccine booster 15–18 years after neonatal immunization. J Infect Dis, 2008; 197(10):1419–1426; doi: 10.1086/587695
30.
MahmoodS, ShahKU, KhanTM. Immune persistence after infant hepatitis-B vaccination: A systematic review and meta-analysis. Sci Rep, 2018; 8(1):12550; doi: 10.1038/s41598-018-30512-8
31.
McMahonBJ, BrudenDL, PetersenKM, et al.Antibody levels and protection after hepatitis B vaccination: results of a 15-year follow-up. Ann Intern Med, 2005; 142(5):333–341; doi: 10.7326/0003-4819-142-5-200503010-00008
32.
MerikiHD, TufonKA, AnongDN, et al.Vaccine uptake and immune responses to HBV infection amongst vaccinated and non-vaccinated healthcare workers, household and sexual contacts to chronically infected HBV individuals in the South West Region of Cameroon. PLoS One, 2018; 13(7):e0200157; doi: 10.1371/journal.pone.0200157
33.
MormileR. Hepatitis B vaccine non response: A predictor of latent autoimmunity?. Med Hypotheses, 2017; 104:45–47; doi: 10.1016/j.mehy.2017.05.020
34.
PoovorawanY, ChongsrisawatV, TheamboonlersA, et al.Evidence of protection against clinical and chronic hepatitis B infection 20years after infant vaccination in a high endemicity region. J Viral Hepatitis, 2011; 18(5):369–375; doi: 10.1111/j.1365-2893.2010.01312.x
35.
QinY, LiaoP. Hepatitis B virus vaccine breakthrough infection: Surveillance of S gene mutants of HBV. Acta Virol, 2018; 62(2):115–121; doi: 10.4149/av_2018_210
36.
RuggieriA, AnticoliS, D'AmbrosioA, et al.The influence of sex and gender on immunity, infection and vaccination. Ann Ist Super Sanita, 2016; 52(2):198–204; doi: 10.4415/ann_16_02_11
37.
SacoTV, StraussAT, LedfordDK. Hepatitis B vaccine nonresponders: Possible mechanisms and solutions. Ann Allergy Asthma Immunol, 2018; 121(3):320–327; doi: 10.1016/j.anai.2018.03.017
38.
SchillieS, MurphyTV, SawyerM, et al.CDC guidance for evaluating health-care personnel for hepatitis B virus protection and for administering postexposure management. MMWR Recomm Rep, 2013; 62(Rr-10):1–19.
39.
SchillieS, VellozziC, ReingoldA, et al.Prevention of hepatitis B virus infection in the United States: Recommendations of the Advisory Committee on Immunization Practices. MMWR Recomm Rep, 2018; 67(1):1–31; doi: 10.15585/mmwr.rr6701a1
40.
SuFH, ChenJD, ChengSH, et al.Seroprevalence of hepatitis-B infection amongst Taiwanese university students 18years following the commencement of a national Hepatitis-B vaccination program. J Med Virol, 2007a;79(2):138–143; doi: 10.1002/jmv.20771
41.
SuFH, ChengSH, LiCY, et al.Hepatitis B seroprevalence and anamnestic response amongst Taiwanese young adults with full vaccination in infancy, 20 years subsequent to national hepatitis B vaccination. Vaccine, 2007b;25(47):8085–8090; doi: 10.1016/j.vaccine.2007.09.013
42.
TrevisanA, GiulianiA, ScapellatoML, et al.Sex disparity in response to hepatitis B vaccine related to the age of vaccination. Int J Environ Res Public Health, 2020; 17(1):327; doi: 10.3390/ijerph17010327
43.
Van Der MeerenO, BehreU, CrastaP. Immunity to hepatitis B persists in adolescents 15–16 years of age vaccinated in infancy with three doses of hepatitis B vaccine. Vaccine, 2016; 34(24):2745–2749; doi: 10.1016/j.vaccine.2016.04.013
44.
WangFS, FanJG, ZhangZ, et al.The global burden of liver disease: The major impact of China. Hepatology, 2014; 60(6):2099–2108; doi: 10.1002/hep.27406
45.
WeiKP, ZhuFC, LiuJX, et al.The efficacy of two different dosages of hepatitis B immunoglobulin combined with hepatitis B vaccine in preventing mother-to-child transmission of hepatitis B virus: A prospective cohort study. Vaccine, 2018; 36(2):256–263; doi: 10.1016/j.vaccine.2017.11.037
46.
XuY, LiuH, WangY, et al.The next step in controlling HBV in China. BMJ, 2013; 347:f4503; doi: 10.1136/bmj.f4503
47.
YanZ, TanW, DanY, et al.Estrogen receptor alpha gene polymorphisms and risk of HBV-related acute liver failure in the Chinese population. BMC Med Genet, 2012; 13:49; doi: 10.1186/1471-2350-13-49
48.
YueT, ZhangQ, CaiT, et al.Trends in the disease burden of HBV and HCV infection in China from 1990–2019. Int J Infect Dis, 2022; 122:476–485; doi: 10.1016/j.ijid.2022.06.017
49.
ZhuCL, LiuP, ChenT, et al.Presence of immune memory and immunity to hepatitis B virus in adults after neonatal hepatitis B vaccination. Vaccine, 2011; 29(44):7835–7841; doi: 10.1016/j.vaccine.2011.07.098
50.
ZhuL, YeK, ZhengY, et al.Effects of hepatitis B vaccine boosters in different levels of epidemic areas on anti-HBs-negative children after primary vaccination. J Med Microbiol, 2021; 70(2); doi: 10.1099/jmm.0.001274.
51.
ZimmermannP, CurtisN. Factors that influence the immune response to vaccination. Clin Microbiol Rev, 2019; 32(2):e00084–18; doi: 10.1128/cmr.00084-18
52.
ZouH, ChenY, DuanZ, et al.Virologic factors associated with failure to passive-active immunoprophylaxis in infants born to HBsAg-positive mothers. J Viral Hepatitis, 2012; 19(2):e18–e25; doi: 10.1111/j.1365-2893.2011.01492.x
53.
ZuckermanJN. Protective efficacy, immunotherapeutic potential, and safety of hepatitis B vaccines. J Med Virol, 2006; 78(2):169–177; doi: 10.1002/jmv.20524
