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ISSN 2097-3497 (Online)
CN 22-1108/R
Volume 37 Issue 6
Jun.  2021
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Article Navigation >  Journal of Clinical Hepatology  > 2021  >  37(6): 1299-1303

Expression of HBcAg in hepatocytes and its association with the efficacy of antiviral therapy

DOI: 10.3969/j.issn.1001-5256.2021.06.017
  • 1.

    Department of Infectious Diseases, Panyu Central Hospital, Guangzhou 511400, China

  • 2.

    Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China

  • 3.

    Department of Prevention and Treatment of Liver Diseases, Jiujiang Third People's Hospital, Jiujiang, Jiangxi 332000, China

  • Received Date: 2020-11-05
  • Accepted Date: 2020-12-22
  • Published Date: 2021-06-20
    Abstract
  •   Objective  To investigate the effect of the expression of HBcAg in hepatocytes on the serum level of HBcAb and seroconversion of HBeAg after antiviral therapy with nucleos(t)ide analogues (NUCs).  Methods  Serum samples and liver tissue paraffin sections were collected from 101 chronic hepatitis B (CHB) patients who received antiviral therapy with NUCs in Nanfang Hospital and Panyu Central Hospital from January 2015 to June 2018. ELISA was used to measure the serum level of HBcAb, and immunohistochemistry was used to measure the expression of HBcAg in the liver. The GEO database (GSE96851) was analyzed to obtain differentially expressed genes in the liver of patients with HBcAg-positive hepatitis. The two-independent-samples t test was used for comparison of continuous data between two groups; the multiple-independent-samples nonparametric Kruskal-Wallis H test was used for comparison of continuous data between multiple groups, and Dunnett method was used for further comparisons; the chi-square test was used for comparison of categorical data between groups.  Results  The expression pattern of HBcAg in hepatocytes was classified as absent expression, nuclear expression, cytoplasmic expression, and nuclear/cytoplasmic expression, and according to expression level, HBcAg expression was classified as grades Ⅰ, Ⅱ, Ⅲ, and Ⅳ expression. HBeAg seroconversion rates after 96 weeks of antiviral therapy were 5.88%, 16.67%, 22.73%, and 24.24%, respectively, in the patients with absent expression, nuclear expression, cytoplasmic expression, and nuclear/cytoplasmic expression (χ2=4.753, P=0.037), and HBeAg seroconversion rates after 96 weeks of antiviral therapy were 5.88%, 13.04%, 27.59%, and 26.67%, respectively, in the patients with grade Ⅰ, Ⅱ, Ⅲ, and Ⅳ expression (χ2=6.580, P=0.016). There were significant differences in the serum levels of HBcAb-IgM and total HBcAb between the patients with absent expression, nuclear expression, cytoplasmic expression, and nuclear/cytoplasmic expression of HBcAg (HBcAb-IgM: H=9.760, P=0.021; total HBcAb: H=21.46, P < 0.001), and there were also significant differences in the serum levels of HBcAb-IgM and total HBcAb between the patients with grade Ⅰ, Ⅱ, Ⅲ, and IV expression of HBcAg (HBcAb-IgM: H=18.80, P < 0.001; total HBcAb: H=26.03, P < 0.001). The analysis of differentially expressed genes in the liver showed that the expression of antibody-related genes was upregulated in the liver of patients with HBcAg-positive acute liver failure.  Conclusion  The expression pattern and level of HBcAg in the cytoplasm of hepatocytes are associated with serum HBcAb, and the measurement of HBcAg may help to predict the efficacy of antiviral therapy with NUCs.

     

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    • References(17)
  • [1]
    Chinese Society of Hepatology and Chinese Society of Infectious Diseases Chinese, Medical Association. The guideline of prevention and treatment for chronic hepatitis B: A 2015 update[J]. J Clin Hepatol, 2015, 31(12): 1941-1960. DOI: 10.3969/j.issn.1001-5256.2015.12.002.

    中华医学会肝病学分会, 中华医学会感染病学分会. 慢性乙型肝炎防治指南(2015年更新版)[J]. 临床肝胆病杂志, 2015, 31(12): 1941-1960. DOI: 10.3969/j.issn.1001-5256.2015.12.002.
    [2]
    YEO YH, HO HJ, YANG HI, et al. Factors associated with rates of HBsAg seroclearance in adults with chronic HBV infection: A systematic review and Meta-analysis[J]. Gastroenterology, 2019, 156(3): 635-646. e9. DOI: 10.1053/j.gastro.2018.10.027.
    [3]
    LOK AS, MCMAHON BJ. Chronic hepatitis B: Update 2009[J]. Hepatology, 2009, 50(3): 661-662. DOI: 10.1002/hep.23190.
    [4]
    LIAW YF, KAO JH, PIRATVISUTH T, et al. Erratum to: Asian-Pacific consensus statement on the management of chronic hepatitis B: A 2012 update[J]. Hepatol Int, 2012, 6(4): 809-810. DOI: 10.1007/s12072-012-9386-z.
    [5]
    LIAW YF, LAU GK, KAO JH, et al. Hepatitis B e antigen seroconversion: A critical event in chronic hepatitis B virus infection[J]. Dig Dis Sci, 2010, 55(10): 2727-2734. DOI: 10.1007/s10620-010-1179-4.
    [6]
    FAN R, SUN J, YUAN Q, et al. Baseline quantitative hepatitis B core antibody titre alone strongly predicts HBeAg seroconversion across chronic hepatitis B patients treated with peginterferon or nucleos(t)ide analogues[J]. Gut, 2016, 65(2): 313-320. DOI: 10.1136/gutjnl-2014-308546.
    [7]
    YUAN Q, SONG LW, LIU CJ, et al. Quantitative hepatitis B core antibody level may help predict treatment response in chronic hepatitis B patients[J]. Gut, 2013, 62(1): 182-184. DOI: 10.1136/gutjnl-2012-302656.
    [8]
    CHI H, LI Z, HANSEN BE, et al. Serum level of antibodies against hepatitis B core protein is associated with clinical relapse after discontinuation of nucleos(t)ide analogue therapy[J]. Clin Gastroenterol Hepatol, 2019, 17(1): 182-191. e1. DOI: 10.1016/j.cgh.2018.05.047.
    [9]
    WANG X, DONG Q, LI Q, et al. Dysregulated response of follicular helper t cells to hepatitis B surface antigen promotes HBV persistence in mice and associates with outcomes of patients[J]. Gastroenterology, 2018, 154(8): 2222-2236. DOI: 10.1053/j.gastro.2018.03.021.
    [10]
    LIU XJ, ZHANG Z. Functional cure of chronic hepatitis B from the perspective of specific immune cells for hepatitis B virus[J]. J Clin Hepatol, 2020, 36(5): 977-979. DOI: 10.3969/j.issn.1001-5256.2020.05.004.

    刘小菊, 张政. 从HBV特异性免疫细胞角度谈慢性乙型肝炎功能性治愈[J]. 临床肝胆病杂志, 2020, 36(5): 977-979. DOI: 10.3969/j.issn.1001-5256.2020.05.004.
    [11]
    SALIMZADEH L, LE BERT N, DUTERTRE CA, et al. PD-1 blockade partially recovers dysfunctional virus-specific B cells in chronic hepatitis B infection[J]. J Clin Invest, 2018, 128(10): 4573-4587. DOI: 10.1172/JCI121957.
    [12]
    MILICH DR, MCLACHLAN A. The nucleocapsid of hepatitis B virus is both a T-cell-independent and a T-cell-dependent antigen[J]. Science, 1986, 234(4782): 1398-1401. DOI: 10.1126/science.3491425.
    [13]
    CHU CM, LIAW YF. Intrahepatic distribution of hepatitis B surface and core antigens in chronic hepatitis B virus infection. Hepatocyte with cytoplasmic/membranous hepatitis B core antigen as a possible target for immune hepatocytolysis[J]. Gastroenterology, 1987, 92(1): 220-225. DOI: 10.1016/0016-5085(87)90863-8.
    [14]
    CHU CM, LIAW YF. Immunohistological study of intrahepatic expression of hepatitis B core and e antigens in chronic type B hepatitis[J]. J Clin Pathol, 1992, 45(9): 791-795. DOI: 10.1136/jcp.45.9.791.
    [15]
    SAITO T, KAMIMURA T, ISHIBASHI M, et al. Electron microscopic study of hepatitis B virus-associated antigens on the infected liver cell membrane in relation to analysis of immune target antigens in chronic hepatitis B[J]. Gastroenterol Jpn, 1992, 27(6): 734-744. DOI: 10.1007/BF02806526.
    [16]
    CHEN HS, WU JF, SU TH, et al. Baseline level of hepatitis B core antibody predicts spontaneous hepatitis B e antigen (HBeAg) seroconversion in HBeAg-positive children with a normal alanine aminotransferase level[J]. Hepatology, 2019, 70(6): 1903-1912. DOI: 10.1002/hep.30788.
    [17]
    VANWOLLEGHEM T, GROOTHUISMINK Z, KREEFFT K, et al. Hepatitis B core-specific memory B cell responses associate with clinical parameters in patients with chronic HBV[J]. J Hepatol, 2020, 73(1): 52-61. DOI: 10.1016/j.jhep.2020.01.024.
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