INTRODUCTION: The immune response against Hepatitis B virus (HBV) represents a key factor for infection outcome. However, the relation between viral replication and host immune reactivity is still a matter of investigation.
AIM: To investigate whether the cellular immune response of newly diagnosed treatment naïve chronic hepatitis B (CHB) patients may be influenced by the replicative status of HBV.
MATERIALS AND METHODS: A total of 45 (17 female and 28 male) newly diagnosed untreated CHB patients aged 42.48±13.19 years (19÷71 years) were enrolled in this study. The patients were divided in two groups according to the viral load: >0÷≤104 copies/ml (n=25) and >10 4÷<108 copies/ml (n=17). Flowcytometric immunophenotyping was performed for evaluation of the cellular immunity. Serum HBV DNA load was assessed by quantitative real-time polymerase chain reaction.
RESULTS: Similar alterations were observed in both patients` groups in comparison with healthy controls which could be summarized as follows: decreased total T cells (CD3+) due to low helper-inducer (CD3+CD4+) and suppressor-cytotoxic (CD3+CD8+) subpopulations; reduced effector cytotoxic (CD8+CD11b-; CD8+CD28+) and activated (CD3+HLA-DR+, CD8+CD38+) T-cell subsets; increased CD57+CD8- cells; elevated percentage of B lymphocytes. No significant differences in the studied immune parameters were detected between both patients` groups except the significantly elevated CD4/CD8 ratio in individuals with higher in comparison to those with lower HBV DNA levels.
CONCLUSION: Alterations in the cellular immune repertoire of CHB patients were observed resulting mainly in significantly decreased T-cell subpopulations, particularly those with effector cell immune phenotype regardless of the viral load.
World Health Organization, `Hepatitis B,` 2012, World Health Organization Fact Sheet, http://www.who.int/mediacentre/ factsheets/fs204/en.
Lavanch D. Hepatitis B virus epidemiology, disease burden, treatment, and current and emerging prevention and control measures. J Viral Hepat. 2004;11:97-107.
Kojuharova М. Prevention of viral hepatitis B in Bulgaria. Department of epidemiology and communicable disease surveillance. National Center of Infectious and Parasitic Diseases, 2011.
Maini MK, Boni C, Lee CK 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;191:1269-1280.
Bertoletti A and Maini MK. Protection or damage: a dual role for the virus specific cytotoxic T lymphocyte response in hepatitis B and C infection? Cur Opin Microbiol. 2000;3:387-392.
Bertoletti A and Gehring A. Immune response and tolerance during hepatitis B virus infection. Hepatol Res. 2007;37,Suppl 3:S331-S338.
Bertoletti A and Gehring A. The immune response during hepatitis B infection. J Gen Virol. 2006;87(6):1439-1449.
Boni C, Penna A, Ogg GS, Bertoletti A, Pilli M, Cavallo C, et al. Lamivudine treatment can overcome cytotoxic T-cell hyporesponsiviness in chronic hepatis B: new perspectives for immune therapy. Hepatology. 2001;33:963-971.
Mukherjee R, Reddy PB, Arava J, Rao P, Mitnala S, Gupta R, Reddy D. Relationship between serum HBsAg level, HBV DNA level, and peripheral immune cells in patients with chronic hepatitis B infection. Hepatic Medicine: Evidence and Research. 2010;2:157-162.
Xibing G, Xiaojuan Y, Zhonghua L, Juanhua W. Alteration in cellular immunity after chronic hepatitis B deteriorated into severe hepatitis and its significance. Hepat Mon. 2011;11(10):810-815.
You J, Sriplung H, Geater A, Chongsuvivatwong V, Zhuang L, Chen HY, et al. Effect of viral load on T-lymphocyte failure in patients with T-lymphocyte B. World J Gastroenterol. 2008;14 (7):1112-1119.
You J, Zhuang L, Zhang YF, Chen HY, Sriplung H, Geater A, et al. Peripheral T-lymphocyte subpopulations in different clinical stages of chronic HBV infection correlate with HBV load. World J Gastroenterol. 2009;15(27):3382-3393.
Sun XH, Liu QL, Li M, Gao YQ. [The study of CD4+ and CD8+ T subsets in chronic hepatitis B patients]. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi (Article in Chinese). 2011;27(5):545-547, 550.
Li X, Kong H, Tian L, Zhu Q, Wang Y, Dong Y, et al. Changes of costimulatory molecule CD28 on circulating CD8+ T cells correlate with disease pathogenesis of chronic hepatitis B. Biomed Res Int. 2014:423181. doi: 10.1155/2014/423181.
Cao W, Qiu ZF, Li TS. Parallel decline of CD8+CD38+ lymphocytes and viremia in treated hepatitis B patients. World J Gastroenterol. 2011;17(17):2191-2198.
Nikolova M, Petrova M, Muhtarova M, Nikolovska D, Krastev Z, Taskov H. Circulating CD8+ T cell subsets and CD39+ T regulatory cells in patients with HBeAg-negative chronic hepatitis B. Probl Infect Parasit Dis. 2001;39(1):34-39.
Ye Y, Liu J, Lai Q, Zhao Q, Peng L, Xie C, et al. Decreases in activated CD8+ T cells in patients with severe hepatitis B are related to outcomes. Dig Dis Sci. 2015;60(1):136-145.
Tan G, Zhao W, Liu X, Wang J, Wu Y. Immunophenotypic profile of intrahepatic and circulating lymphocytes in chronic hepatitis B patients. Hepatogastroenterology. 2012;59(117):1516-1521.
Sun H, Lv J, Tu Z, Hu X, Yan H, Pan Y, et al. Antiviral treatment improves disrupted peripheral B lymphocyte homeostasis in chronic hepatitis B virus-infected patients. Exp Biol Med (Maywood). 2013;238(11):1275-1283.
Zhao PW, Jia FY, Shan YX, Ji HF, Feng JY, Niu JQ, Ayana DA, Jiang YF. Downregulation and altered function of natural killer cells in hepatitis B virus patients treated with entecavir. Clin Exp Pharmacol Physiol. 2013;40(3):190-196.
Diao H, He J, Zheng Q, Chen J, Cui G, Wei Y, et al. A possible role for NKT-like cells in patients with chronic hepatitis B during telbivudine treatment. Immunol Lett. 2014;160:66-71.