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Abstract

Hepatitis B infection is a major public health issue with a high mortality rate. It is caused by hepatitis B virus (HBV), a small incomplete hepadnavirus with several open reading frames (ORF). High mutation rates of the HBV ORFs due to the virus’ replicating strategy are associated with the development and emergence of mutant strains, which may result in occult infections that are undetectable by conventional diagnostic assays. In this study, we first investigated the presence and prevalence of hepatitis B surface antigen (HBsAg) and HBV DNA among 204 patients visiting the specialist hospital in Osogbo, Nigeria, by using the Acumen diagnostic test strip kit and PCR amplification of the surface antigen gene. Then, we compared the positive results detected by both assays. The mean age of the participants was 30.5 years. Twenty-two (10.78%) cases were positive in the HBsAg test, and 69 (33.82%) cases were positive for HBV DNA. Fifty-four false-negatives (26.47%) and four false-positives (1.96%) were detected by HBsAg. The rapid diagnostic test kit is less sensitivity and has lower detection capability compared with the PCR-based assay, which indicates the presence of mutant HBV strain(s). The results of this work demonstrate that HBsAg is endemic in Nigeria and that HBV DNA is highly prevalent among the population. Our findings highlight the need for immediate action to prevent the further spread of infection.

References

[1] Block, T.M., Guo, H., Guo, J. 2007. Molecular virology of hepatitis B virus for clinicians. Clin Liver Dis. 11(4): 685–706, https://doi.org/10.101 6/j.cld.2007.08.002.

[2] Glebe, D., König, A. 2014. Molecular virology of hepatitis B virus and targets for antiviral intervention. Intervirol. 57: 134–140, https://doi.or g/10.1159/000360946.

[3] Gerlich, W.H. 2013. Medical virology of hepatitis B: How it began and where we are now. Virol. J. 10(239): 1–25, https://doi.org/10.1186/1743-422X-10-239.

[4] Brooks, G.F., Carroll, K.C., Butel, J.S., Morse, S.A., Mietzner, T.A. 2014. Jawetz, Melnick and Adelberg’s Medical Microbiology, 26th ed. Singapore: McGraw Hill Education. pp. 521.

[5] World Health Organization. 2019. Hepatitis B Key Facts. https://www.who.int/en/news-room/fact-shee ts/detail/hepatitis-b.

[6] Arora, D.R., Arora, B.B. 2016. Textbook of Microbiology, 5th ed. New Delhi, India: CBS Publishers and Distributors. Pp. 535–547.

[7] Song, J.E., Kim, D.Y. 2016. Diagnosis of hepatitis B. Ann. Transl. Med. 4(18): 1–6, https://doi.org/1 0.21037/atm.2016.09.11.

[8] Torbenson, M., Thomas, D.L. 2002. Occult hepatitis B. Lancet Infect. Dis. 2(8): 479–486, https://doi.o rg/10.1016/s1473-3099(02)00345-6.

[9] Ghosh, M., Nandi, S., Dutta, S., Saha, M.K. 2015. Detection of hepatitis B virus infection: A systematic review. World J. Hepatol. 7(23): 2482–2491, https://doi.org/10.4254/wjh.v7.i23.2482.

[10] Ghouri, Y.A., Mian, I., Rowe, J.H. 2017. Review of hepatocellular carcinoma: Epidemiology, etiology and carcinogenesis. J. Carcinog. 16(1), https://doi.org/10.4103/jcar.JCar_9_16.

[11] Raimondo, G., Allain, J.P., Brunetto, M.R., Buendia, M.A., Chen, D.S., Colombo, M., Craxì, A., Donato, F., Ferrari, C., Gaeta, G.B., Gerlich, W.H., Levrero, M., Locarnini, S., Michalak, T., Mondelli, M.U., Pawlotsky, J.M., Pollicino, T., Prati, D., Puoti, M., Samuel, D., Shouval, D., Smedile, A., Squadrito, G., Trépo, C., Villa, E., Will, H., Zanetti, A.R., Zoulim, F. 2008. Statements from the Taormina expert meeting on occult hepatitis B virus infection. J. Hepatol. 49: 652–657, https://doi.org/10.1016/j.jh ep.2008.07.014.

[12] Makvandi, M. 2016. Update on occult hepatitis B virus infection. World J. Gastroenterol. 22(39): 8720–8734, https://doi.org/10.3748/wjg.v22.i39.8720.

[13] Nishikawa, H., Osaki, Y. 2013. Clinical significance of occult hepatitis B infection in progression of liver disease and carcinogenesis. J. Cancer. 4(6): 473–480, https://doi.org/10.7150/jca.6609.

[14] Pollicino, T., Saitta, C. 2014. Occult hepatitis B virus and hepatocellular carcinoma. World J. Gastroenterol. 20(20): 5951–5961, https://doi.org/ 10.374 8/wjg.v20.i20.5951.

[15] Biswas, A., Panigrahi, R., Chandra, P.K., Banerjee, A., Datta, S., Pal, M., Chakraborty, S., Bhattacharya, P., Chakrabarti, S., Chakravarty, R. 2013. characterization of the occult hepatitis B virus variants circulating among the blood donors from Eastern India. Sci. World J. 2013: 1–7, https://doi.org/ 10.1155/2013/212704.

[16] Elkady, A., Iijima, S., Aboulfotuh, S., Ali, E.M., Sayed, D., Abdel-Aziz, N.M., Ali, A.M., Murakami, S., Isogawa, M., Tanaka, Y. 2017. Characteristics of escape mutations from occult hepatitis B virus infected patients with hematological malignancies in South. Egypt World J. Hepatol. 9(9): 477–486, https://doi.org/10.4254/wjh.v9.i9.477.

[17] Diarra, B., Yonli,, A.T., Sorgho, P.A., Compaore, T.R., Ouattara, A.K., Zongo, W.A., Tao, I., Traore, L., Soubeiga, S.T., Djigma, F.W., Obiri-Yeboah, D., Nagalo, B., Pietra, V., Sanogo, R., Simpore, J. 2018. Occult Hepatitis B Virus Infection and Associated Genotypes among HBsAg-negative Subjects in Burkina Faso. Mediterr J. Hematol Infect. Dis. 10(1): e2018007, https://doi.org/10.4084/MJHID. 20 18.007.

[18] Caligiuri, P., Cerruti, R., Icardi, G., Bruzzone, B. 2016. Overview of hepatitis B virus mutations and their implications in the management of infection. World J. Gastroenterol. 22(1): 145–154, https://doi.o rg/10.3748/wjg.v22.i1.145.

[19] Kessler, H.H., Stelzl, E., Marth, E., Stauber, R.E. 2003. Detection of mutations in the hepatitis B virus polymerase gene. Clin. Chem. 49(6 Pt 1): 989–992, https://doi.org/10.1373/49.6.989.

[20] Tuteja, A., Siddiqui, A.B., Madan, K., Goyal, R., Shalimar, S.V., Kaur, N., Panda, S.K., Narayanasamy, K., Subodh, S., Acharya, S.K. 2014. Mutation profiling of the hepatitis B virus strains circulating in North Indian population. PLoS ONE. 9(3): e91150, https://doi.org/10.1371/journal. pone.0 091150.

[21] Saffioti, F., Raimondo, G. 2017. What do we know about occult hepatitis B virus infection? Atti della Accademia Peloritana dei Pericolanti-Classe di Scienze Medico-Biologiche. 105(2): 1–13, https://doi.o rg/10.6092/1828-6550.

[22] Nainan, O.V., Khristova, M.L., Byun, K., Xia, G., Taylor, P.E., Stevens, C.E., Margolis, H.S. 2002. Genetic variation of hepatitis B surface antigen coding region among infants with chronic hepatitis B virus infection. J Med Virol. 68: 319–327, https://doi.org/10.1002/jmv.10206.

[23] La’ulu, S.L., Roberts, W.L. 2006. The analytic sensitivity and mutant detection capability of six hepatitis B surface antigen assays. Am. J. Clin. Pathol. 125: 748–751, https://doi.org/10.1309/K5E M-795V-NGGF-GBXX.

[24] Vivekanandan, P., Kannangai, R, Ray, S.C., Thomas, D.L., Torbenson, M. 2008. Comprehensive genetic and epigenetic analysis of occulthepatitis B from liver tissue samples. Clin. Infect. Dis. 46(8): 1227–1236, https://doi.org/10.1086/529437.

[25] Hass, M., Hannoun, C., Kalinina, T., Sommer, G., Manegold, C., Guther, S. 2005. Functional analysis of hepatitis B virus reactivating in hepatitis B surface antigen-negative individuals. Hepatol. 42: 93–103, https://doi.org/10.1002/hep.20748.

[26] Samal, J., Kandal, M., Vivekananda, P. 2012. Molecular mechanisms underlying occult hepatitis B virus infection. Clin. Microbiol Rev. (25): 142–163.

[27] Foy, C., Thio, L., Hwang, S., Sauynas, M., Hamilton, P., Fine, M., Atta, G. 2012. False negative hepatitis B virus (HBV) Surface antigen in a vaccinated dialysis patient with a high level of HBV DNA in the United States. Clin. Vaccine Immunol. 19(5): 820–822, https://doi.org/10.1128/CVI.05696-11.

[28] Kwak, M., Kim, Y.J. 2014. Occult hepatitis B virus infection. World J. Hepatol. 6(12): 860–869, https://doi.org/10.4254/wjh.v6.i12.860.

[29] Oluyinka, O.O., Tong, H.V., Bui, T.S., Fagbami, A.H., Adekanle, O., Ojurongbe, O., Thomas, C.B., Kremsner, P.G., Velavan, T.P. 2015. Occult hepatitis B virus infection in Nigerian blood donors and hepatitis B virus transmission risks. PLoS ONE. 10(7): e0131912, https://doi.org/10.1371/journal.

[30] Faleye, C.O., Adewunmi, O.M., Ifeorah, M.I., Omoniyi, C.E., Bakarey, A.S., Akere, A., Awokunle, F., Ajibola, O.H., Makanjuola, O.D., Adeniji, A.J. 2015. Detection of hepatitis B virus isolates with mutations associated with immune escape mutants among pregnant women in Ibadan, South-western Nigeria, SpringerPlus. 4: 43, https://doi.org/10.1186/s40064-015-0813-1.0.

[31] World Health Organization. 2015. Guidelines for the prevention, care and treatment of persons with chronic Hepatitis B infection. http://www.who.int. hiv/topics/hepatitis/en/.

[32] Obi, R.K., Umeh, S.C., Okurede, O.H., Iroagba, I.I. 2006. Prevalence of hepatitis B virus infection among pregnant women in an antenatal clinic in Port Harcourt, Nigeria. Afr. J. Clin. Experiment Microbiol. 7: 78–82, https://doi.org/10.4314/ ajcem.v7i2.7 434.

[33] Olokoba, A.B., Salawu, F.K., Danburam, A. 2011. Hepatitis B virus infection amongst pregnant women in North-Eastern Nigeria- A call for action. Niger. J Clin. Pract. 14(1): 10–13, https://doi.org/ 10.4103/1119-3077.79232.

[34] Eke, A.C., Eke, U.A., Okafor, C.I., Ezebialu, I.U., Ogbuagu, C. 2011. Prevalence, correlates and pattern of hepatitis B surface antigen in a low resource setting. Virol. J. 8: 12, https://doi.org/10.1186/ 1743-422X-8-12.

[35] Lazarevic, I. 2014. Clinical implications of hepatitis B virus mutation: Recent advances. World J. Gastroenterol. 20(24): 7653–7664, https://doi.org/1 0.3748/wjg.v20.i24.7653.

[36] Erhabor, O., Kwaifa, I.K., Bayawa, A.M., Isaac, Z.I., Dorcas, I., Sani, I. 2014. Comparison of ELISA and rapid screening techniques for the detection of HBsAg among blood donors in Usmanu Danfodiyo University Teaching Hospital Sokoto, North Western Nigeria. J. Blood Lymph. 4: 124, https://doi.org/10.4172/2165-7831.1000124.

[37] Gish, R.G., Gutierrez, J.A., Navarro-Cazarez, N., Giang, K., Adler, D., Tran, B., Locarnini, S., Hammond, R., Bowden, S. 2014. A simple and inexpensive point-of-care test for hepatistis B surface antigen detection: Serological and molecular evaluation. J. Viral Hepatitis. 21(12): 905–908, https://doi.org/1 0.1111/jvh.12257.

[38] Allen, L., Deslauriers, M., Andrew, S.W., Triples, A., Walters, K., Tyrell, J., Brown, N., Lynn, D. 1998. Identification and characterization of mutation is hepatitis B virus Resistant to lamivudine. Hepatol. 27(6): 1670–1677.

[39] Anjum, Q. 2014. False positive hepatitis B surface antigen due to recent vaccination. Int. J. Health Sci. (Qassim). 8(2): 189–193, https://www.ncbi.nlm.ni h.gov/pmc/articles/PMC4166991/.

[40] Mair, D.C., Brecher, M.E., Hom, E., Owen, H.G., Shea, T.C. 1996. False-positive hepatitis B surface antigen screening test results in patients receiving granulocyte-colony-stimulating factor. Transfusion. 36(11–12): 948–951, https://doi.org/10.1046/j.153 7-2995.1996.36111297091735.x.

[41] Tang, D.M., Heller, T., Koh, C. 2016. The many faces of positive hepatitis B surface antigen hepatol. 64(4): 1379–1381, https://doi.org/10.1002/ hep.285 03.

[42] Gatti,S., Gramegna, M., Bisoffi, Z., Raglio, A., Gulletta, M., Klersy, C., Bruno, A., Maserati, R., Madama, S., Scaglia, M., Gispi Study Group. 2007. A comparison of three diagnostic techniques for malaria: A rapid diagnostic test (NOW Malaria), PCR and microscopy. Ann. Trop. Med. Parasitol. 101(3): 195–204, https://doi.org/10.1179/ 136485907X1569 97.

[43] Alam, M.S., Mohon, A.N., Mustafa, S., Khan, W.A., Islam, N., Karim, M.J., Khanum, H., Sullivan Jr, D.J., Haque, R. 2011. Real-time PCR assay and rapid diagnostic tests for the diagnosis of clinically suspected malaria patients in Bangladesh. Malar. J. 10(175), https://doi.org/10.1186/1475-2875-10-175.

[44] Mishra, R.K., Tiwari, Y.K., Pundir, S., Saraf, G., Pawan, K., Dashora, D., Pokra, M., Patidar, V., Rana, J. 2017. A comparison of rapid card test with Enzyme-linked immunosorbent assay for the detection of hepatitis B surface antigen [HBsAg] in tertiary care hospital. Res. Rev. J. Microbiol Virol. 7(3): 27–31, www.stmjournals.com.

[45] Wei, Z., Zhang, X., Wei, C., Yao, L., Li, Y., Zhang, X., Xu, H., Jia, Y., Guo, R., Wu, Y., Yang, K., Gao, X. 2019. Diagnostic accuracy of in-house real-time PCR assay for Mycobacterium tuberculosis: a systematic review and meta-analysis. BMC Infect. Dis. 19(701), https://doi.org/10.1186/s12879-019-4273-z.

[46] Cai, H.X., Zhang, X. 2020. Landscape Coronavirus Disease 2019 test (COVID-19 test) in vitro–A comparison of PCR vs Immunoassay vs Crispr-Based test. 1–13, https://doi.org/10.31219/osf.io/6e agn.

[47] Maignan, M., Viglino, D., Hablot, M., Termoz, Masson, N., Lebeugle, A., Muret, R.C., Makele, P.M., Guglielmetti, V., Morand, P., Lupo, J., Forget, V., Lanndelle, C., Larrat, S. 2019. Diagnostic accuracy of a rapid RT-PCR assay for point-of-care detection of influenza A/B virus at emergency department admission: A prospective evaluation during the 2017/2018 influenza season. PLOS ONE. 14(5): e0216308, https://doi.org/10.1371/journal. pone.021 6308.

[48] Shen, X., Qiu, F., Shen, L., Yan, T., Zhao, M., Qi, J., Chen, C., Zhao, L., Wang, L., Feng, Z., Ma, X. 2019. A rapid and sensitive recombinase aided amplification assay to detect hepatitis B virus without DNA extraction. BMC Infect. Dis. 19(229), https://doi.org/10.1186/s12879-019-3814-9.

[49] Vashist, S.K. 2020. In vitro diagnostic assays for covid-19: Recent advances and emerging trends. Diagn. 10(202): 1–7, https://doi.org/10.3390/diagnos tics10040202.

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