中文English
ISSN 1001-5256 (Print)
ISSN 2097-3497 (Online)
CN 22-1108/R
Volume 39 Issue 1
Jan.  2023
Turn off MathJax
Article Contents

Serum levels of soluble programmed death-1 and soluble programmed death-ligand 1 in chronic hepatitis B patients with clinical cure and their clinical features

DOI: 10.3969/j.issn.1001-5256.2023.01.008
Research funding:

Beijing Municipal Science and Technology Commission of Major Projects (D171100003117005);

Beijing Municipal Science and Technology Commission of Major Projects (D161100002716003)

More Information
  • Corresponding author: XU Xiaoyuan, xiaoyuanxu6@163.com (ORCID: 0000-0002-1759-4330)
  • Received Date: 2022-09-06
  • Published Date: 2023-01-20
  •   Objective  To investigate the serum levels of soluble programmed death-1 (sPD-1) and soluble programmed death-ligand 1 (sPD-L1) in chronic hepatitis B (CHB) patients with clinical cure, the correlation between programmed death-1 (PD-1) and lymphocytes by flow cytometry, and the recovery of hepatitis B virus (HBV)-specific immunity.  Methods  A total of 26 CHB patients with clinical cure, 26 treatment-naïve CHB patients, and 26 healthy controls who were diagnosed at the outpatient service of Peking University First Hospital from January to May of 2022 were enrolled, and related clinical data and peripheral blood samples were collected. ELISA was used to measure the serum levels of sPD-1 and sPD-L1, and flow cytometry was used to measure the expression of PD-1 in peripheral blood lymphocytes. CHB patients with clinical cure were compared with the treatment-naïve CHB patients and the healthy controls. The Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between three groups, and the chi-square test was used for comparison of categorical data between groups. The Pearson correlation analysis or the Spearman correlation analysis was used to investigate the correlation between two continuous variables.  Results  For the 26 CHB patients with clinical cure, the mean time of antiviral therapy was 8.33 years, with entecavir as the antiviral drug. The CHB patients with clinical cure had significantly higher levels of sPD-1 and sPD-L1 than the healthy controls (P < 0.05) and significantly lower percentages of PD-1+ cells/lymphocytes and PD-1+CD8+ T cells/lymphocytes than the treatment-naïve CHB patients (P < 0.05). In the treatment-naïve CHB patients, the serum levels of sPD-1 and sPD-L1 were moderately negatively correlated with HBsAg level (r=-0.524 and -0.583, both P < 0.05). The serum levels of sPD-1 and sPD-L1 were moderately positively correlated with PD-1+CD8+ T cells/lymphocytes (r=0.535 and 0.419, both P < 0.05). In the CHB patients with clinical cure, the serum levels of sPD-1 and sPD-L1 were not correlated with age, sex, alanine aminotransferase, T cells/lymphocytes, CD8+ T cells/lymphocytes, PD-1+ T cells/lymphocytes or PD-1+CD8+ T cells/lymphocytes (all P > 0.05).  Conclusion  The serum levels of sPD-1 and sPD-L1 in treatment-naïve CHB patients are mainly associated with exhausted CD8+ T cells in peripheral blood, while there is no significant correlation between serum sPD-1/sPD-L1 and exhausted CD8+ T cells in peripheral blood in CHB patients with clinical cure.

     

  • loading
  • [1]
    European Association for the Study of the Liver. EASL 2017 clinical practice guidelines on the management of hepatitis B virus infection[J]. J Hepatol, 2017, 67(2): 370-398. DOI: 10.1016/j.jhep.2017.03.021.
    [2]
    TERRAULT NA, LOK ASF, MCMAHON BJ, et al. Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance[J]. Hepatology, 2018, 67(4): 1560-1599. DOI: 10.1002/hep.29800.
    [3]
    ZHANG WH, ZHANG DZ, DOU XG. Consensus on pegylated interferon alpha in treatment of chronic hepatitis B[J]. Chin J Hepatol, 2017, 25(9): 678-686. DOI: 10.3760/cma.j.issn.1007-3418.2017.09.007.

    张文宏, 张大志, 窦晓光, 等. 聚乙二醇干扰素α治疗慢性乙型肝炎专家共识[J]. 中华肝脏病杂志, 2017, 25(9): 678-686. DOI: 10.3760/cma.j.issn.1007-3418.2017.09.007.
    [4]
    BUTI M, TSAI N, PETERSEN J, et al. Seven-year efficacy and safety of treatment with tenofovir disoproxil fumarate for chronic hepatitis B virus infection[J]. Dig Dis Sci, 2015, 60(5): 1457-1464. DOI: 10.1007/s10620-014-3486-7.
    [5]
    Chinese Society of Infectious Diseases, Chinese Medical Association, Chinese Society of Hepatology, Chinese Medical Association. Guidelines for the prevention and treatment of chronic hepatitis B (version 2019)[J]. J Clin Hepatol, 2019, 35(12): 2648-2669. DOI: 10.3969/j.issn.1001-5256.2019.12.007.

    中华医学会感染病学分会, 中华医学会肝病学分会. 慢性乙型肝炎防治指南(2019年版)[J]. 临床肝胆病杂志, 2019, 35(12): 2648-2669. DOI: 10.3969/j.issn.1001-5256.2019.12.007.
    [6]
    LAI CL, WONG D, IP P, et al. Reduction of covalently closed circular DNA with long-term nucleos(t)ide analogue treatment in chronic hepatitis B[J]. J Hepatol, 2017, 66(2): 275-281. DOI: 10.1016/j.jhep.2016.08.022
    [7]
    LIU J, YANG HI, LEE MH, et al. Spontaneous seroclearance of hepatitis B seromarkers and subsequent risk of hepatocellular carcinoma[J]. Gut, 2014, 63(10): 1648-1657. DOI: 10.1136/gutjnl-2013-305785.
    [8]
    BERTOLETTI A, FERRARI C. Adaptive immunity in HBV infection[J]. J Hepatol, 2016, 64(1 Suppl): S71-S83. DOI: 10.1016/j.jhep.2016.01.026.
    [9]
    CHAO DT, LIM JK, AYOUB WS, et al. Systematic review with meta-analysis: the proportion of chronic hepatitis B patients with normal alanine transaminase ≤ 40 IU/L and significant hepatic fibrosis[J]. Aliment Pharmacol Ther, 2014, 39(4): 349-358. DOI: 10.1016/j.jhep.2016.01.026.
    [10]
    NGUYEN LH, CHAO D, LIM JK, et al. Histologic changes in liver tissue from patients with chronic hepatitis B and minimal increases in levels of alanine aminotransferase: a meta-analysis and systematic review[J]. Clin Gastroenterol Hepatol, 2014, 12(8): 1262-1266. DOI: 10.1016/j.cgh.2013.11.038.
    [11]
    YE B, LIU X, LI X, et al. T-cell exhaustion in chronic hepatitis B infection: current knowledge and clinical significance[J]. Cell Death Dis, 2015, 6(3): e1694. DOI: 10.1038/cddis.2015.42.
    [12]
    XU P, CHEN YJ, CHEN H, et al. The expression of programmed death-1 in circulating CD4+ and CD8+ T cells during hepatitis B virus infection progression and its correlation with clinical baseline characteristics[J]. Gut Liver, 2014, 8(2): 186-195. DOI: 10.5009/gnl.2014.8.2.186.
    [13]
    ZHANG Z, ZHANG JY, WHERRY EJ, et al. Dynamic programmed death 1 expression by virus-specific CD8 T cells correlates with the outcome of acute hepatitis B[J]. Gastroenterology, 2008, 134(7): 1938-1949, 1949. e1-3. DOI: 10.1053/j.gastro.2008.03.037.
    [14]
    KASSEL R, CRUISE MW, IEZZONI JC, et al. Chronically inflamed livers up-regulate expression of inhibitory B7 family members[J]. Hepatology, 2009, 50(5): 1625-1637. DOI: 10.1002/hep.23173.
    [15]
    YANG S, ZENG W, ZHANG J, et al. Restoration of a functional antiviral immune response to chronic HBV infection by reducing viral antigen load: if not sufficient, is it necessary?[J]. Emerg Microbes Infect, 2021, 10(1): 1545-1554. DOI: 10.1080/22221751.2021.1952851.
    [16]
    XIA J, HUANG R, CHEN Y, et al. Profiles of serum soluble programmed death-1 and programmed death-ligand 1 levels in chronic hepatitis B virus-infected patients with different disease phases and after anti-viral treatment[J]. Aliment Pharmacol Ther, 2020, 51(11): 1180-1187. DOI: 10.1111/apt.15732.
    [17]
    ZHOU L, LI X, HUANG X, et al. Soluble programmed death-1 is a useful indicator for inflammatory and fibrosis severity in chronic hepatitis B[J]. J Viral Hepat, 2019, 26(7): 795-802. DOI: 10.1111/jvh.13055.
    [18]
    van BUUREN N, RAMIREZ R, TURNER S, et al. Characterization of the liver immune microenvironment in liver biopsies from patients with chronic HBV infection[J]. Jhep Rep, 2022, 4(1): 100388. DOI: 10.1016/j.jhepr.2021.100388.
    [19]
    LUCKHEERAM RV, ZHOU R, VERMA AD, et al. CD4+T cells: differentiation and functions[J]. Clin Dev Immunol, 2012, 2012: 925135. DOI: 10.1155/2012/925135.
    [20]
    RINKER F, ZIMMER CL, HÖNER ZU SIEDERDISSEN C, et al. Hepatitis B virus-specific T cell responses after stopping nucleos(t)ide analogue therapy in HBeAg-negative chronic hepatitis B[J]. J Hepatol, 2018, 69(3): 584-593. DOI: 10.1016/j.jhep.2018.05.004.
    [21]
    YUEN MF, WONG DK, FUNG J, et al. HBsAg seroclearance in chronic hepatitis B in Asian patients: replicative level and risk of hepatocellular carcinoma[J]. Gastroenterology, 2008, 135(4): 1192-1199. DOI: 10.1053/j.gastro.2008.07.008.
    [22]
    CHANG JJ, THOMPSON AJ, VISVANATHAN K, et al. The phenotype of hepatitis B virus-specific T cells differ in the liver and blood in chronic hepatitis B virus infection[J]. Hepatology, 2007, 46(5): 1332-1340. DOI: 10.1002/hep.21844.
  • 加载中

Catalog

    通讯作者: 陈斌, bchen63@163.com
    • 1. 

      沈阳化工大学材料科学与工程学院 沈阳 110142

    1. 本站搜索
    2. 百度学术搜索
    3. 万方数据库搜索
    4. CNKI搜索

    Tables(4)

    Article Metrics

    Article views (1719) PDF downloads(109) Cited by()
    Proportional views
    Related

    /

    DownLoad:  Full-Size Img  PowerPoint
    Return
    Return