Occult hepatitis B virus infection in people with haemophilia in South Africa

O Kgotleng; N Msomi; LD Mthethwa; J Potgieter; JN Mahlangu; M Karodia; NL Ntabeni

doi:10.2478/jhp-2025-0009

Abstract

Abstract Background

Occult hepatitis B virus (HBV) infection (OBI) is defined as the presence of HBV DNA in the absence of HBV surface antigen (HBsAg) serological markers. Despite the high prevalence of HBV infection in many communities, OBI prevalence among people with haemophilia (PWH) remains poorly characterised in South Africa.

Aims

The aim of the study was to determine the prevalence of OBI and characterise viral complications of patients attending haemophilia clinics in three tertiary hospitals in Gauteng, namely, the Steve Biko Academic Hospital (SBAH), Charlotte Maxeke Johannesburg Academic Hospital (CMJAH) and Dr George Mukhari Academic Hospital (DGMAH).

Methods

This descriptive cross-sectional study was approved by the ethics committees of each participant centre. Haemophilia patients of any severity or inhibitor status with positive serological markers of HBV infection and immunity were excluded from the study. We measured Hepatitis B DNA of those with negative serological markers using a quantitative hepatitis B PCR assay.

Results

Of the 76 patients screened, 66 male patients were included in the study. The median age was 29 years. Haemophilia A and haemophilia B comprised 89% and 11% of the cohort, respectively. The majority of patients were taking prophylactic factor replacement therapy (72%) as opposed to episodic therapy (28%). A total of 10 patients (15%) had inhibitors. Five patients (8%) were HIV seropositive. Ten patients (15%) had no documented evidence of being vaccinated against hepatitis B infection. Anti-hepatitis B core antibodies were positive in 5 patients (8%). All patients had a negative hepatitis B surface antigen result. All patients demonstrated negative hepatitis B PCR results.

Conclusion

In this cohort of PWH from 3 centres, none showed evidence of occult HBV infection.

Article

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References

1. World Health Organization. Global hepatitis report 2024: Action for access in low-and middle-income countries. April 2024. Available from https://www.who.int/publications/i/item/9789240091672 (accessed May 2025).
2. World Health Organization. Hepatitis B. Available from https://www.who.int/en/news-room/fact-sheets/detail/hepatitis-b (accessed May 2025).
3. Zampino R, Boemio A, Sagnelli C, et al. 2015. Hepatitis B virus burden in developing countries. World J Gastroenterol 2015; 21(42):11941. doi: https://doi.org/10.3748/wjg.v21.i42.11941.
4. Schweitzer A, Horn J, Mikolajczyk RT, et al. Estimations of worldwide prevalence of chronic hepatitis B virus infection: A systematic review of data published between 1965 and 2013. Lancet 2015; 386(10003):1546–55. doi: https://doi.org/10.1016/S0140-6736(15)61412-X.
5. Kiire C. The epidemiology and prophylaxis of hepatitis B in sub-Saharan Africa: A view from tropical and subtropical Africa. Gut 1996; 38(Suppl 2): S5–12. doi: https://doi.org/10.1136/gut.38.suppl_2.s5.
6. Kew MC. Hepatitis B virus infection: The burden of disease in South Africa. Southern African Journal of Epidemiology and Infection 2008; 23(1): 4–8. doi: https://doi.org/10.1080/10158782.2008.11441293.
7. Shi Y, Zheng M. Hepatitis B virus persistence and reactivation. BMJ 2020; 370: m2200. doi: https://doi.org/10.1136/bmj.m2200
8. Yip TCF, Wong GLH. Current knowledge of occult hepatitis B infection and clinical implications. Semin Liver Dis 2019; 39(2): 249–60. doi: https://doi.org/10.1055/s-0039-1678728.
9. Raimondo G, Locarnini S, Pollicino T, et al. Update of the statements on biology and clinical impact of occult hepatitis B virus infection. J Hepatol 2019; 71(2):397–408. doi: https://doi.org/10.1016/j.jhep.2019.03.034
10. Ocana S, Casas ML, Buhigas I, Lledo JL. Diagnostic strategy for occult hepatitis B virus infection. World J Gastroenterol 2011; 17(12):1553. doi: https://doi.org/10.3748/wjg.v17.i12.1553.
11. Kramvis A. Molecular characteristics and clinical relevance of African genotypes and subgenotypes of hepatitis B virus. S Afr Med J 2018; 108(8):17–21. doi: https://doi.org/10.7196/samj.2018.v108i8.13495.
12. Hwang EW, Cheung R. Global epidemiology of hepatitis B virus (HBV) infection. North American Journal of Medicine and Science 2011; 4(1):7–13. Available from https://najms.com/index.php/najms/article/view/499 (accessed May 2025).
13. Im YR, Jagdish R, Leith D, et al. Prevalence of occult hepatitis B virus infection in adults: A systematic review and meta-analysis. Lancet Gastroenterol Hepatol 2022; 7(10): 932–42. doi: https://doi.org/10.1016/S2468-1253(22)00201-1.
14. Weusten J, Van Drimmelen H, Vermeulen M, Lelie N. A mathematical model for estimating residual transmission risk of occult hepatitis B virus infection with different blood safety scenarios. Transfusion 2017; 57(3pt2): 841–9. doi: https://doi.org/10.1111/trf.14050.
15. Candotti D, Boizeau L, Laperche S. Occult hepatitis B infection and transfusion-transmission risk. Transfus Clin Biol 2017; 24(3): 189–95. doi: https://doi.org/10.1016/j.tracli.2017.06.014.
16. Makris M, Preston F, Triger D, et al. Hepatitis c antibody and chronic liver disease in haemophilia. Lancet 1990; 335(8698): 1117–9. doi: https://doi.org/10.1016/0140-6736(90)91124-S.
17. Merritt EC. Infected blood scandal: Background, impacts, interim compensation and inquiry outcomes. [cited 2024; 2024/08/05]. Available from: https://lordslibrary.parliament.uk/infected-blood-scandal-background-impacts-interim-compensation-and-inquiry-outcomes.
18. Teitel JM. Viral safety of haemophilia treatment products. Ann Med 2000; 32(7):485–92. doi: https://doi.org/10.3109/07853890009002024.
19. Allain JO, Belkhiri D, Vermeulen M, et al. Characterization of occult hepatitis B virus strains in South African blood donors. Hepatology 2009; 49(6): 1868–76. doi: https://doi.org/10.1002/hep.22879.
20. Bell TG, Makondo E, Martinson NA, Kramvis A. Hepatitis B virus infection in human immunodeficiency virus infected southern African adults: Occult or overt–that is the question. PLoS One 2012; 7(10): e45750. doi: https://doi.org/10.1371/journal.pone.0045750.
21. Msomi N|, Ndlovu K, Gianhari J, et al. High rate of occult hepatitis B virus infection in hemodialysis units of KwaZulu-Natal, South Africa. J Med Virol 2019; 91(10): 1797–803. doi: https://doi.org/10.1002/jmv.25510.
22. Javanmard D, Namaei MH, Farahmand M, et al. Molecular and serological characterization of occult hepatitis B virus infection among patients with hemophilia. J Med Virol 2019; 91(8): 1519–27. doi: https://doi.org/10.1002/jmv.25470.
23. Toyoda H, Hayashi K, Murakami Y, et al. Prevalence and clinical implications of occult hepatitis b viral infection in hemophilia patients in Japan. J Med Virol 2004; 73(2): 195–9. doi: https://doi.org/10.1002/jmv.20075.
24. Varaklioti A, Kouramba A, Ioannidou P, Katsarou O. Occult hepatitis B virus infection in Greek patients with congenital bleeding disorders. Infect Genet Evol 2017; 54: 397–401. doi: https://doi.org/10.1016/j.meegid.2017.07.012.
25. Windyga J, Brojer E, Gronowska A, et al. Preliminary results of HBV DNA testing of Polish haemophilia patients–lack of occult HBV infection. Haemophilia 2006; 12(4): 380–3. doi: https://doi.org/10.1111/j.1365-2516.2006.01293.x.
26. Spearman CW, Afihene M, Ally R, et al. Hepatitis B in sub-Saharan Africa: Strategies to achieve the 2030 elimination targets. Lancet Gastroenterol Hepatol 2017; 2(12): 900–9. doi: https://doi.org/10.1016/S2468-1253(17)30295-9.
27. Vermeulen M, Swanevelder R, Van Zyl G, Lelie N, Murphy EL. An assessment of hepatitis B virus prevalence in South African young blood donors born after the implementation of the infant hepatitis B virus immunization program: Implications for transfusion safety. Transfusion 2021; 61(9): 2688–700. doi: https://doi.org/10.1111/trf.16559.
28. European Medicines Agency. Guideline on plasma-derived medicinal products. 21 July 2011. EMA/CHMP/BWP/706271/2010. Available from https://www.ema.europa.eu/en/documents/scientific-guideline/guideline-plasma-derived-medicinal-products_en.pdf (accessed June 2025).
29. Samal J, Kandpal M. Vivekandandan P. Molecular mechanisms underlying occult hepatitis B virus infection. Clin Microbiol Rev 2012; 25(1): 142–63. doi: https://doi.org/10.1128/CMR.00018-11.

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Authors

O Kgotleng

Department of Haematology, National Health Laboratory Service ; University of Pretoria, South Africa
N Msomi

Discipline of Virology, National Health Laboratory Service ; University of KwaZulu Natal, South Africa
LD Mthethwa

Discipline of Virology, National Health Laboratory Service ; University of KwaZulu Natal, South Africa
J Potgieter

Department of Haematology, National Health Laboratory Service ; University of Pretoria, South Africa
JN Mahlangu

Department of Molecular Medicine and Haematology, Faculty of Health Science, National Health Laboratory ; University of Witwatersrand, South Africa
M Karodia

Division of Clinical Haematology, Gauteng Department of Health ; University of Sefako Makgatho, South Africa
NL Ntabeni

lumka.ntabeni@up.ac.za

Department of Haematology, National Health Laboratory Service ; University of Pretoria, South Africa .