Despite access to efficient hepatitis B virus (HBV) vaccine and universal immunization schedules, HBV infection remains a global health concern. HBV infection has decreased by this program. Nevertheless, breakthrough infections occur due to generation of occult HBV infection (OBI) and surface gene mutants in the immunized population. We aimed to determine the presence of OBI in a population born after initiation of nationwide HBV vaccination in Tehran, Iran. A HBV mass vaccination schedule was launched in Iran in 1993. For this study, we enrolled 1120 cases younger than 24 years. ELISA was applied to evaluate the presence of HBsAg, anti-HBs and anti-HBc. HBV-DNA presence was determined in all HBsAg-negative cases using nested polymerase chain reaction. The prevalence of HBsAg, anti-HBc and anti-HBs was 0.1, 0.54 and 39.9% respectively. Out of 6 anti-HBc-positive individuals, 4 cases also had anti-HBs. One case revealed HBsAg co-existence and the other one showed isolated anti-HBc. HBV-DNA was not detected in HBsAg-negative specimens. A very low prevalence of HBsAg and isolated anti-HBc was observed and no occult HBV infection was detected. It seems that evasion mutants are not a potential threat for HBV universal immunization efficacy in the vaccinated population.
This is a preview of subscription content, access via your institution.
Buy single article
Instant access to the full article PDF.
Tax calculation will be finalised during checkout.
El-Seraq HB. Hepatocellular carcinoma. N Engl J Med. 2011;365(12):1118–27. https://doi.org/10.1056/NEJMra1001683.
van der Sande MA, Waight PA, Mendy M, Zaman S, Kaye S, Sam O et al. Long-term protection against HBV chronic carriage of Gambian adolescents vaccinated in infancy and immune response in HBV booster trial in adolescence. PLoS One. 2007;2(8):e753. https://doi.org/10.1371/journal.pone.0000753.
Chang MH. Breakthrough HBV infection in vaccinated children in Taiwan. Surveillance for HBV mutants. Antivir Ther. 2010;15:463–9. https://doi.org/10.3851/IMP1555.
McMahon BJ, Bruden DL, Petersen KM, Bulkow LR, Parkinson AJ, et al. Antibody levels and protection after hepatitis B vaccination: results of a 15-year follow up. Ann Intern Med. 2005;142:333–41. https://doi.org/10.7326/0003-4819-142-5-200503010-00008.
Ngui SL, Andrews NJ, Underhill GS, Heptonstall J, Teo CG. Failed postnatal immunoprophylaxis for hepatitis B: characteristics of maternal hepatitis B virus as risk factors. Clin Infect Dis. 1998;27:100–6.
Raimondo G, Locarnini S, Pollicino T, Levrero M, Zoulim F, et al. Update of the statements on biology and clinical impact of occult hepatitis B virus infection. J Hepatol. 2019;71(2):397–408.
Aghakhani A, Mohraz M, Aghasadeghi MR, Banifazl M, Vahabpour R, et al. Occult hepatitis B virus infection and S gene escape mutants in HIV-infected patients after hepatitis B virus vaccination. Int J STD Aids. 2016;27(11):967–72. https://doi.org/10.1177/0956462415602419.
Aghakhani A, Banifazl M, Kalantar E, Eslamifar A, Ahmadi F, Razeghi E, et al. Occult hepatitis B virus infection in hemodialysis patients with isolated hepatitis B core antibody. A multicenter study. Ther Apher Dial. 2010;14(3):349–53. https://doi.org/10.1111/j.1744-9987.2009.00798.x.
Azadmanesh K, Mohraz M, Aghakhani A, Edalat R, Jam S, Eslamifar A et al. Occult hepatitis B virus infection in HIV-infected patients with isolated hepatitis B core antibody. Intervirology. 2008;51(4):270–4. https://doi.org/10.1159/000160217.
Seto WK, Chan TS, Hwang YY, Wong DK, Fung J, Liu KS, et al. Hepatitis B reactivation in occult viral carriers undergoing hematopoietic stem cell transplantation: a prospective study. Hepatology. 2017;65:1451–61.
Hsu HY, Chang MH, Ni YH, Chiang CL, Wu JF, Chen HL. Universal infant immunization and occult hepatitis B virus infection in children and adolescents: a population-based study. Hepatology. 2015;61:1183–91.
Ramezani A, Aghasadeghi MR, Ahmadi F, Razeghi E, Eslamifar A, Banifazl M, et al. Isolated anti-hbc and occult HBV infection in dialysis patients. Nephrourol Mon. 2014;7(1):e22674. https://doi.org/10.5812/numonthly.22674.
Saitta C, Tripodi G, Barbera A, Bertuccio A, Smedile A, Ciancio A, et al. Hepatitis B virus (HBV) DNA integration in patients with occult HBV infection and hepatocellular carcinoma. Liver Int. 2015;35:2311–7.
Lusida M, Juniastuti, Yano Y. Current hepatitis B virus infection situation in Indonesia and its genetic diversity. World J Gastroenterol. 2016;22(32):7264–74. https://doi.org/10.3748/wjg.v22.i32.7264.
Ponde RA. Molecular mechanisms underlying HBsAg negativity in occult HBV infection. Eur J Clin Microbiol Infect Dis. 2015;34:1709–31.
Torbenson M, Thomas DL. Occult hepatitis B. Lancet Infect Dis. 2002;2:479–86. https://doi.org/10.1016/S1473-3099(02)00345-6.
Kim H, Kim BJ. Association of preS/S mutations with occult hepatitis B virus (HBV) infection in South Korea. Transmission potential of distinct occult HBV variants. Int J Mol Sci. 2015;16(6):13595–609. https://doi.org/10.3390/ijms160613595.
Teo CG, Locarnini S. Potential threat of drug-resistant and vaccine-escape HBV mutants to public health. Antivir Ther. 2010;15:445–9.
Huang C‑H, Yuan Q, Chen PJ, Zhang YL, Chen CR, Zheng QB, et al. Influence of mutations in hepatitis B virus surface protein on viral antigenicity and phenotype in occult HBV strains from blood donors. J Hepatol. 2012;57(4):720–9.
World Health Organization. Expanded programme on immunization. Global advisory group. Wkly Epidemiol Rec. 1992;67:11–6.
Luo Z, Li L, Ruan B. Impact of the implementation of a vaccination strategy on hepatitis B virus infections in China over a 20-year period. Int J Infect Dis. 2012;16(2):e82–8. https://doi.org/10.1016/j.ijid.2011.10.009.
Lavanchy D. Hepatitis B virus epidemiology, disease burden, treatment, and current and emerging prevention and control measures. J Viral Hepat. 2004;11(2):97–107.
Nelson NP, Easterbrook PJ, McMahon BJ. Epidemiology of hepatitis B virus infection and impact of vaccination on disease. Clin Liver Dis. 2016;20(4):607–28.
Chen CJ, Wang LY, Yu MW. Epidemiology of hepatitis B virus infection in the Asia–Pacific region. J Gastroenterol Hepatol. 2000;15:E3–E6.
Basuni AA, Butterworth L, Cooksley G, Locarnini S, Carman WF. Prevalence of HBsAg mutants and impact of hepatitis B infant immunisation in four Pacific Island countries. Vaccine. 2004;22:2791–9. https://doi.org/10.1016/j.vaccine.2004.01.046.
Fitzsimons D, François G, Hall A, McMahon B, Meheus A, et al. Long-term efficacy of hepatitis B vaccine, booster policy, and impact of hepatitis B virus mutants. Vaccine. 2005;23:4158–66. https://doi.org/10.1016/j.vaccine.2005.03.017.
Viviani S, Jack A, Hall AJ, Maine N, Mendy M, et al. Hepatitis B vaccination in infancy in The Gambia: protection against carriage at 9 years of age. Vaccine. 1999;17:2946–50. https://doi.org/10.1016/S0264-410X(99)00178-4.
Komas NP, Vickos U, Hübschen JM, Béré A, Manirakiza A, et al. Cross-sectional study of hepatitis B virus infection in rural communities, Central African Republic. BMC Infect Dis. 2013;13:286.
Lee KM, Kim YS, Ko YY, Yoo BM, Lee KJ, et al. Emergence of vaccine-induced escape mutant of hepatitis B virus with multiple surface gene mutations in a Korean child. J Korean Med Sci. 2001;16(3):359–62. https://doi.org/10.3346/jkms.2001.16.3.359.
Lin YM, Jow GM, Mu SC, Chen BF. Naturally occurring hepatitis B virus B‑cell and T‑cell epitope mutants in hepatitis B vaccinated children. ScientificWorldJournal. 2013;2013:571875. https://doi.org/10.1155/2013/571875.
Kabir A, Alavian SM, Ahanchi N, Malekzadeh R. Combined passive and active immunoprophylaxis for preventing perinatal transmission of the hepatitis B virus in infants born to HBsAg positive mothers in comparison with vaccine alone. Hepatol Res. 2006;36(4):265–71. https://doi.org/10.1016/j.hepres.2006.08.001.
Esteghamati A, Keshtkar AA, Nadjafi L, Gouya MM, Salaramoli M, Roshandel G, et al. Hepatitis B vaccination coverage among Iranian children aged 15–26 months in 2006. East Mediterr Health J. 2011;17(2):93–100.
Alavian SM, Fallahian F, Lankarani KB. The changing epidemiology of viral hepatitis B in Iran. J Gastrointestin Liver Dis. 2007;16(4):403–6. https://doi.org/10.1111/j.1542-4758.2008.00284.x.
Alavian SM, Hajariazdeh B, Ahmadzad Asl M, Kabir A, Bagheri Lankarani KB. Hepatitis B virus infection in Iran: a systematic review. Hepat Mon. 2008;8(4):281–94.
Li T, Fu Y, Allain J‑P, Li C. Chronic and occult hepatitis B virus infections in the vaccinated Chinese population. Ann Blood. 2017; https://doi.org/10.21037/aob.2017.04.02.
Fortuin M, Karthigesu V, Allison L, Howard C, Hoare S, et al. Breakthrough infections and identification of a viral variant in Gambian children immunized with hepatitis B vaccine. J Infect Dis. 1994;169:1374–6.
Paul S, Saxena A, Terrin N, Viveiros K, Balk EM, Wong JB. Hepatitis B virus reactivation and prophylaxis during solid tumor chemotherapy: a systematic review and meta-analysis. Ann Intern Med. 2016;164:30–40.
Yokoyama K, Kumagai H, Takahashi M, Nagashima S, Okamoto H, Yamagata T. Occult hepatitis B virus infection in immunized children born to carrier mothers. Pediatr Int. 2017;59(9):1010–6.
Amponsah-Dacosta E, Lebelo RL, Rakgole JN, Selabe SG, Gededzha MP, et al. Hepatitis B virus infection in postvaccination South Africa: occult HBV infection and circulating surface gene variants. J Clin Virol. 2015;63:12–7. https://doi.org/10.1016/j.jcv.2014.11.032.
Mu SC, Lin YM, Jow GM, Chen BF. Occult hepatitis B virus infection in hepatitis B vaccinated children in Taiwan. J Hepatol. 2009;50(2):264–72. https://doi.org/10.1016/j.jhep.2008.09.017.
Hsu HY, Chang MH, Ni YH, Chen HL. Survey of hepatitis B surface variant infection in children 15 years after a nationwide vaccination program in Taiwan. Gut. 2004;53(10):1499–503. https://doi.org/10.1136/gut.2003.034223.
Hsu HY, Chang MH, Liaw SH, Ni YH, Chen HL. Changes of hepatitis B surface antigen variants in carrier children before and after universal vaccination in Taiwan. Hepatology. 1999;30(5):1312–7. https://doi.org/10.1002/hep.510300511.
Ni YH, Chang MH, Wu JF, Hsu HY, Chen HL, Chen DS. Minimization of hepatitis B infection by a 25-year universal vaccination program. J Hepatol. 2012;57(4):730–5. https://doi.org/10.1016/j.jhep.2012.05.021.
Darmawan E, Turyadi, El-Khobar KE, Nursanty NK, Thedja MD, Muljono DH. Seroepidemiology and occult hepatitis B virus infection in young adults in Banjarmasin, Indonesia. J Med Virol. 2015;87(2):199–207. https://doi.org/10.1002/jmv.24045.
Elrashidy H, El-Didamony G, Elbahrawy A, Hashim A, Alashker A, et al. Absence of occult hepatitis B virus infection in sera of diabetic children and adolescents following hepatitis B vaccination. Hum Vaccin Immunother. 2014;10(8):2336–41. https://doi.org/10.4161/hv.29521.
Lai MW, Lin TY, Tsao KC, Huang CG, Hsiao MJ, et al. Increased seroprevalence of HBV DNA with mutations in the S gene among individuals greater than 18 years old after complete vaccination. Gastroenterology. 2012;143(2):400–7. https://doi.org/10.1053/j.gastro.2012.05.002.
Aghasadeghi MR, Velayati AA, Mamishi S, Nabavi M, Aghakhani A, et al. Low prevalence of hepatitis B vaccine escape mutants among individuals born after the initiation of a nationwide vaccination program in Iran. Arch Virol. 2016;161(12):3405–11. https://doi.org/10.1007/s00705-016-3050-1.
The authors are grateful to Pasteur Institute of Iran for financial support of this study.
This study was financially supported by Pasteur Institute of Iran, Tehran, Iran
Conflict of interest
M.R. Aghasadeghi, A. Aghakhani, S. Mamishi, F. Bidari-Zerehpoosh, M.-T.H. Ashtiani, S. Sabeti, M. Banifazl, A. Karami, A. Bavand, and A. Ramezani declare that they have no competing interests.
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
About this article
Cite this article
Aghasadeghi, M.R., Aghakhani, A., Mamishi, S. et al. No evidence of occult HBV infection in population born after mass vaccination. Wien Med Wochenschr 170, 218–223 (2020). https://doi.org/10.1007/s10354-020-00748-z
- Expanded program of immunization
- Chronic hepatitis B
- Occult HBV