SEROLOGICAL STRUCTURE OF IMMUNE STATUS TO HEPATITIS B VIRUS UNDER LONG-TERM VACCINATION
Abstract
Background. A significant proportion of hepatitis B virus-related chronic liver diseases and their adverse outcomes remain a major global health challenge. Under implementation of long-term routine vaccination programs, population immune status assessment is crucial for epidemiological surveillance. Objective. To assess the structure of population immune status to hepatitis B virus (HBV) based on combinations of anti-HBs and anti-HBc markers under implementation of long-term vaccination programs. Material and methods. A cross-sectional seroepidemiological study with a retrospective analysis of HBV immune status was conducted among the population of the Republic of Belarus. Serological markers were determined using an enzyme-linked immunosorbent assay (ELISA) for detection of HBsAg, antibodies to the viral surface antigen (anti-HBs), and total antibodies to the HB-core antigen (anti-HBc). The primary endpoints were the presence of anti-HBs and anti-HBc, while the secondary endpoints were their combination and association with age and vaccination status. A serum anti-HBs concentration of 10 mIU/mL or higher was considered seroprotective. Results. In the total cohort of 1,548 individuals examined, protective anti-HBs levels were detected in 54.26% (95% CI 51.77–56.73), reflecting the proportion of individuals in the population with signs of established immunity. Additionally, the proportion of individuals with signs of exposure to the virus (anti-HBc+, including those combined with anti-HBs) accounted to 15.65% (95% CI 13.77–17.63), significantly exceeding the proportion of post-infection immunity and reflecting the presence of a group of individuals with isolated anti-HBc. This indicates a significant contribution of natural circulation of the virus to the immunity formation. Conclusion. Serological heterogeneity of population immunity has been established in the population of the Republic of Belarus across different age groups, administrative territories, and vaccination statuses. The population immune structure regarding HBV includes post-vaccination and post-infection components, as well as a group of individuals with uncertain immune status, which should be considered in hepatitis B surveillance.
References
World Health Organization. Hepatitis B [Internet]. Available from: https://www.who.int/publications/i/item/9789240103986
Cui F, Blach S, Manzengo Mingiedi C, Gonzalez MA, Sabry Alaama A, Mozalevskis A, Séguy N, Rewari BB, Chan PL, Le LV, Doherty M, Luhmann N, Easterbrook P, Dirac M, de Martel C, Nayagam S, Hallett TB, Vickerman P, Razavi H, Lesi O, Low-Beer D. Global reporting of progress towards elimination of hepatitis B and hepatitis C. Lancet Gastroenterol Hepatol. 2023;8(4):332-342. https://doi.org/10.1016/S2468-1253(22)00386-7.
World Health Organization. Global hepatitis report, 2017 [Internet]. Available from: https://www.who.int/publications/i/item/9789241565455
World Health Organization. Guidelines on hepatitis B and C testing. Geneva: WHO; 2017. 204 p.
United Nations Office for Disaster Risk Reduction (UNDRR); International Science Council (ISC). UNDRR-ISC Hazard Information Profiles – 2025 Update: BI0212 Hepatitis B United Nations Office for Disaster Risk Reduction; International Science Council [Internet]. Available from: https://www.undrr.org/terms/hips/BI0212
Pattyn J, Hendrickx G, Vorsters A, Van Damme P. Hepatitis B Vaccines. J Infect Dis. 2021;224(12 Suppl 2):S343-S351. https://doi.org/10.1093/infdis/jiaa668.
Kolomiets ND, Vysotskaya VS, Glinskaya IN, Dashkevich AM, Romanova ON, Gasich EL. Vlijanie universalnoj vakcinacii na rasprostranjonnost gepatita B sredi naselenija Respubliki Belarus [Influence of universal vaccination on the prevalence of hepatitis B among the population of the Republic of Belarus]. In: Akimkin VG, editor. Virusnyje gepatity – dostizhenija i novyje perspektivy. Sbornik tezisov XIV Vserosijskoj konferencii s mezhdunarodnym uchastiem; 2024 Sent. 12-13; Moskva. Moskva : FBUN CNII Epidemiologii Rospotrebnadzora; 2024. p. 53. (Russian).
Vysotskaya V, Kolomiets N, Glinskaya I, Romanova O, Gasich E, Samoilovich E. Ocenka vozdejstvija vakcinacii v Respublike Belarus na jepidemicheskij process gepatita В [Assessment of the impact of vaccination in the republic of Belarus on the epidemic process of hepatitis B]. Gepatologija i gastroenterologija [Hepatology and Gastroenterology]. 2023;7(1):48-56. https://doi.org/10.25298/2616-5546-2023-7-1-48-56. https://www.elibrary.ru/pdfidc. (Russian).
Vysotskaya V, Gassowski M, Kasper A, Gasich E, Kolomiets N, Dashkevich A, Wannemuehler K, Dubovik O, Mosina L. Hepatitis B serosurvey to validate the achievement of regional hepatitis B control targets in Belarus. Vaccine. 2025;55:127058. https://doi.org/10.1016/j.vaccine.2025.127058
Immunization Action Coalition (IAC). Ask the Experts: Hepatitis B [Internet]. Available from: https://www.immunize.org/ask-experts/topic/hepb/
Leuridan E, Van Damme P. Hepatitis B and the need for a booster dose. Clin Infect Dis. 2011;53(1):68-75. https://doi.org/10.1093/cid/cir270.
Fitzsimons D, François G, Hall A, McMahon B, Meheus A, Zanetti A, Duval B, Jilg W, Böcher WO, Lu SN, Akarca U, Lavanchy D, Goldstein S, Banatvala J, Damme PV. Long-term efficacy of hepatitis B vaccine, booster policy, and impact of hepatitis B virus mutants. Vaccine. 2005;23(32):4158-66. https://doi.org/10.1016/j.vaccine.2005.03.017.
Thomas B, Mohandas A, Jayadev VK, Bindu V. Hepatitis B Surface Antibody Levels among Health-Care Personnel Vaccinated against Hepatitis B in a Teaching Hospital in South India. Indian J Community Med. 2022;47(2):262-265. https://doi.org/10.4103/ijcm.ijcm_600_21.
Conners EE, Panagiotakopoulos L, Hofmeister MG, Spradling PR, Hagan LM, Harris AM, Rogers-Brown JS, Wester C, Nelson NP. Screening and Testing for Hepatitis B Virus Infection: CDC Recommendations – United States, 2023. MMWR Recomm Rep. 2023;72(1):1-25. https://doi.org/10.15585/mmwr.rr7201a1.
Gish RG, Basit SA, Ryan J, Dawood A, Protzer U. Hepatitis B Core Antibody: Role in Clinical Practice in 2020. Curr Hepatology Rep. 2020;19:254-265. https://doi.org/10.1007/s11901-020-00522-0.
Makvandi M. Update on occult hepatitis B virus infection. World J Gastroenterol. 2016;22(39):8720-8734. https://doi.org/10.3748/wjg.v22.i39.8720.
Raimondo G, Locarnini S, Pollicino T, Levrero M, Zoulim F, Lok AS; Taormina Workshop on Occult HBV Infection Faculty Members. Update of the statements on biology and clinical impact of occult hepatitis B virus infection. J Hepatol. 2019;71(2):397-408. https://doi.org/10.1016/j.jhep.2019.03.034.
Chang JJ, Mohtashemi N, Bhattacharya D. Significance and Management of Isolated Hepatitis B Core Antibody (Anti-HBc) in HIV and HCV: Strategies in the DAA Era. Curr HIV/AIDS Rep. 2018;15(2):172-181. https://doi.org/10.1007/s11904-018-0379-y.
Magomedova NA, Kostinov MP, Khrapunova IA, Linok AV, Loktionova MN, Polishchuk VB, Yastrebova NE, Poddubikov AA. Chastota vstrechaemosti anti-HBc v gruppah medicinskih rabotnikov, neprivityh i vakcinirovannyh protiv gepatita B bez predvaritelnogo testirovanija na markery VGV [The prevalence of anti-HBc antibodies in groups of medical workers who were either unvaccinated or vaccinated against hepatitis B without prior testing for HBV markers]. Infekcija i immunitet [Russian Journal of Infection and Immunity]. 2025;15(5):955-964. https://doi.org/10.15789/2220-7619-TPO-17857. (Russian).
Hyun CS, Lee S, Ventura WR. The prevalence and significance of isolated hepatitis B core antibody (anti-HBc) in endemic population. BMC Res Notes. 2019;12(1):251. https://doi.org/10.1186/s13104-019-4287-z.
Wang C, Li X, Zhang C, Xiao L, Xian J. Prevalence and influential factors of isolated hepatitis B core antibody positivity in a Chinese adult population. Sci Rep. 2024;14(1):693. https://doi.org/10.1038/s41598-023-50907-6.
1.png)
