Dynamics of Hepatitis B Virus Surface Antigen Level with Peripheral Blood Lymphocytes in Chronic Hepatitis B Infection

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Shuaibu Abdullahi Hudu
Saadatu Haruna Shinkafi
Shuaibu Umar
Babazhitsu Makun


Background: Peripheral blood mononuclear cells containing an aggregate of immune competent cells, such as T lymphocytes, B cells and natural killer cells, play an important role in control or persistence of the hepatitis B virus (HBV) infection. Similarly, the expression of hepatitis B viral antigens on the surface of infected hepatocytes can invoke a cytotoxic T–cell response.

Objective: To investigate the dynamic changes in hepatitis B surface antigen (HBsAg) and peripheral lymphocyte subsets of healthy donors and chronic hepatitis B patients.

Methodology: Serum HBsAg was quantified by enzyme-linked immunosorbent assay according to the manufacturer’s guidelines. Peripheral blood lymphocyte cell phenotyping was carried out by flow cytometry for all chronic hepatitis B patients and healthy blood donors.

Results: The results of this study showed a significant correlation between HBsAg level and percentage of T and NK cells (r=0.366; P=0.01, r=-0.462; P=0.01, respectively). On the other hand, significance variation in peripheral blood lymphocyte percentage of T lymphocyte subsets in patients were found to be directly proportional to T cell subsets CD4+and CD8+ (P=0.001) compared with healthy blood donor controls.

Conclusion: In conclusion this study highlighted the role of the HBsAg level in supressing the immune cells of the innate and adaptive immune system. Understanding the interactions between HBsAg and peripheral blood cells serves as a basis for development of HBV therapeutic vaccines and a prognostic biomarker in persistent HBV infection.

Therapeutic vaccine, prognostic biomarker, chronic HBV infection, HBsAg

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How to Cite
Hudu, S. A., Shinkafi, S. H., Umar, S., & Makun, B. (2020). Dynamics of Hepatitis B Virus Surface Antigen Level with Peripheral Blood Lymphocytes in Chronic Hepatitis B Infection. Journal of Advances in Medicine and Medical Research, 32(7), 1-9. https://doi.org/10.9734/jammr/2020/v32i730443
Original Research Article


Maity SN, Kumar S, Vijayaraghavan R, Polavarapu R. An update on hepatitis B virus. International Research in Medical and Health Science. 2018;1(1):8-11.

Ugwuja E, Ugwu N. Seroprevalence of hepatitis B surface antigen and liver function tests among adolescents in Abakaliki, South Eastern Nigeria. The Internet Journal of Tropical Medicine. 2010;6(2):1726-32.

Ndako JA, Echeonwu G, Nwankiti O, Onovoh E, Ujah A, Ikani P, et al. Hepatitis B virus sero-prevalence among pregnant females in northern Nigeria. Res J Med Sci. 2012;6(3):129-133.

Musa B, Bussell S, Borodo M, Samaila A, Femi O. Prevalence of hepatitis B virus infection in Nigeria, 2000-2013:A systematic review and meta-analysis. Niger J Clin Pract. 2015;18(2):163-72.

Zhao H, Zhou YH. Revaccination against hepatitis B in late teenagers who received vaccination during infancy: Yes or no? Hum Vaccin Immunother. 2018;14(2):456-63.

Indolfi G, Easterbrook P, Dusheiko G, Siberry G, Chang M-H, Thorne C, et al. Hepatitis B virus infection in children and adolescents. Lancet Gastroenterol Hepatol. 2019;4(6):466-76.

Chisari FV, Isogawa M, Wieland SF. Pathogenesis of hepatitis B virus infection. Pathol Biol (Paris). 2010;58(4):258-66.

Bertoletti A, Gehring AJ. The immune response during hepatitis B virus infection. J Gen Virol. 2006;87(6):1439-49.

Bertoletti A, Ferrari C, Fiaccadori F. Role of the cell-mediated immune response in the pathogenesis of hepatitis B virus infection: Possible immune-therapeutic strategies. Acta Biomed Ateneo Parmense Parma: Società di medicina e scienze naturali di Parma. 1996;67(3-4):87.

Maier H, Isogawa M, Freeman GJ, Chisari FV. PD-1: PD-L1 interactions contribute to the functional suppression of virus-specific CD8+ T lymphocytes in the liver. J Immunol. 2007;178(5):2714-20.

Alireza K, Mohsen A, Sudabeh A, Hiedeh D, Farideh B, Mohammad-Hossein A. Compositional changes of PBL population in patients with chronic hepatitis B virus infection. Braz J Infect Dis. 2001;5(6):345-51.

Liu B, Li J, Han Y, Liu Y, Kong L, Cao Y, et al. Dynamic analysis of lymphocyte subsets of peripheral blood in patients with acute self-limited hepatitis B. Health. 2010; 2(7):736-41.

Ciupe SM, Ribeiro RM, Nelson PW, Dusheiko G, Perelson AS. The role of cells refractory to productive infection in acute hepatitis B viral dynamics. Proc Natl Acad Sci. 2007;104(12):5050-5.

Maini M, Bertoletti A. How can the cellular immune response control hepatitis B virus replication? J Viral Hepat. 2000;7(5):321-6.

Penna A, Chisari FV, Bertoletti A, Missale G, Fowler P, Giuberti T, et al. Cytotoxic T lymphocytes recognize an HLA-A2-restricted epitope within the hepatitis B virus nucleocapsid antigen. J Exp Med. 1991;174(6):1565-70.

Alexander G, Mondelli M, Naumov N, Nouriaria K, Vergani D, Lowe D, et al. Functional characterization of peripheral blood lymphocytes in chronic HBsAg carriers. Clin Exp Immunol. 1986;63(3): 498.

Regenstein FG, Roodman ST, Perrillo RP. Immunoregulatory T cell subsets in chronic hepatitis B virus infection: The influence of homosexuality. Hepatology. 1983;3(6): 951-4.

Robayes G, De Groote J, Vandeputte M. Suppressor cell function in liver disease. Lancet. 1983;2:342.

Milich DR, Chen MK, Hughes JL, Jones JE. The secreted hepatitis B precore antigen can modulate the immune response to the nucleocapsid: A mechanism for persistence. J Immunol. 1998;160(4):2013-21.

Chen MT, Billaud JN, Sällberg M, Guidotti LG, Chisari FV, Jones J, et al. A function of the hepatitis B virus precore protein is to regulate the immune response to the core antigen. Proc Natl Acad Sci USA. 2004; 101(41):14913-8.

Chan HLY, Wong VWS, Tse AML, Tse CH, Chim AML, Chan HY, et al. Serum hepatitis B surface antigen quantitation can reflect hepatitis B virus in the liver and predict treatment response. Clin Gastro-enterol Hepatol. 2007;5(12):1462-8.

Moucari R, Mackiewicz V, Lada O, Ripault MP, Castelnau C, Martinot‐Peignoux M, et al. Early serum HBsAg drop: A strong predictor of sustained virological response to pegylated interferon alfa‐2a in HBeAg‐negative patients. Hepatology. 2009;49(4):1151-7.

Seeger C, Mason WS. Hepatitis B virus biology. Microbiol Mol Biol Rev. 2000;64 (1):51-68.

Op den Brouw ML, Binda RS, Van Roosmalen MH, Protzer U, Janssen HL, Van Der Molen RG, et al. Hepatitis B virus surface antigen impairs myeloid dendritic cell function: A possible immune escape mechanism of hepatitis B virus. Immunology. 2009;126(2):280-9.

Carey I, D'Antiga L, Bansal S, Longhi MS, Ma Y, Mesa IR, et al. Immune and viral profile from tolerance to hepatitis B surface antigen clearance: A longitudinal study of vertically hepatitis B virus-infected children on combined therapy. J Virol. 2011;85(5): 2416-28.

Tuaillon E, Mondain A-M, Nagot N, Ottomani L, Kania D, Nogue E, et al. Comparison of serum HBsAg quantitation by four immunoassays and relationships of HBsAg level with HBV replication and HBV genotypes. PloS One. 2012;7(3):e32143.

Wherry EJ, Ha SJ, Kaech SM, Haining WN, Sarkar S, Kalia V, et al. Molecular signature of CD8+ T cell exhaustion during chronic viral infection. Immunity. 2007;27(4):670-84.

Kimura K, Kakimi K, Wieland S, Guidotti LG, Chisari FV. Activated intrahepatic antigen-presenting cells inhibit hepatitis B virus replication in the liver of transgenic mice. J Immunol. 2002;169(9):5188-95.

Ferrari C, Penna A, Bertoletti A, Valli A, Antoni AD, Giuberti T, et al. Cellular immune response to hepatitis B virus-encoded antigens in acute and chronic hepatitis B virus infection. J Immunol. 1990;145(10):3442-9.

Maini MK, Boni C, Lee CK, Larrubia JR, Reignat S, Ogg GS, et al. The role of virus-specific CD8+ cells in liver damage and viral control during persistent hepatitis B virus infection. J Exp Med. 2000;191(8): 1269-80.

Edwards M. Hepatitis B serology—help in interpretation. Pediatr Clin North Am. 1988;35(3):503.

Biswas R, Tabor E, Hsia CC, Wright DJ, Laycock ME, Fiebig EW, et al. Comparative sensitivity of HBV NATs and HBsAg assays for detection of acute HBV infection. Transfusion. 2003;43(6):788- 98.

Choong MU, Ton SH, Cheong SK. The cellular immune status of HBsAg positive carriers in Malaysia. Asian Pac J Allergy Immunol. 2011;14(1):19.

Rossol S, Marinos G, Carucci P, Singer MV, Williams R, Naoumov NV. Interleukin-12 induction of Th1 cytokines is important for viral clearance in chronic hepatitis B. J Clin Invest. 1997;99(12):3025.

Mukherjee RM, Reddy PB, Arava J, Rao P, Reddy D. Relationship between serum HBsAg level, HBV DNA level, and peripheral immune cells in patients with chronic hepatitis B virus infection. Hepat Med. 2010;2:157-62.

You J, Sriplung H, Geater A, Chongsuvivatwong V, Zhuang L, Chen H-Y, et al. Effect of viral load on T-lymphocyte failure in patients with chronic hepatitis B. World J Gastroenterol. 2008; 14(7):1112.

Kalams SA, Walker BD. The critical need for CD4 help in maintaining effective cytotoxic T lymphocyte responses. J Exp Med. 1998;188(12):2199-204.

Chu CM, Liaw YF. Peripheral Tcell subsets in asymptomatic hepatitis B-virus carriers. Cell Immunol. 1986;98(2):533-7.

Livingston BD, Alexander J, Crimi C, Oseroff C, Celis E, Daly K, et al. Altered helper T lymphocyte function associated with chronic hepatitis B virus infection and its role in response to therapeutic vaccination in humans. J Immunol. 1999; 162(5):3088-95.

Al-Kayat R, Ghadah MS, Muhammad AZ, Salih DS, Zqair AK. Study of t-lymphocytes subsets in patients with hbv chronic carriers. Journal of Al-Nahrain University-Science. 2007;10(1):130-5.

Barnaba V, Musca A, Cordova C, Levrero M, Ruocco G, Albertini-Petroni V, et al. Relationship between T cell subsets and suppressor cell activity in chronic hepatitis B virus (HBV) infection. Clin Exp Immunol. 1983;53(2):281.

Hyodo N, Tajimi M, Ugajin T, Nakamura I, Imawari M. Frequencies of interferon-γ and interleukin-10 secreting cells in peripheral blood mononuclear cells and liver infiltrating lymphocytes in chronic hepatitis B virus infection. Hepatol Res. 2003;27(2): 109-16.

Cooper S, Erickson AL, Adams EJ, Kansopon J, Weiner AJ, Chien DY, et al. Analysis of a successful immune response against hepatitis C virus. Immunity. 1999; 10(4):439-49.

Loggi E, Bihl FK, Cursaro C, Granieri C, Galli S, Brodosi L, et al. Virus-Specific Immune Response in HBeAg-Negative Chronic Hepatitis B: Relationship with Clinical Profile and HBsAg Serum Levels. PloS One. 2013;8(6):e65327.

Chen Y, Wei H, Sun R, Tian Z. Impaired function of hepatic natural killer cells from murine chronic HBsAg carriers. Int Immunopharmacol. 2005;5(13):1839-52.