中文English
ISSN 1001-5256 (Print)
ISSN 2097-3497 (Online)
CN 22-1108/R
Volume 39 Issue 5
May  2023
Turn off MathJax
Article Contents

Value of combined baseline serum HBV markers in predicting HBeAg seroconversion in chronic hepatitis B patients treated by nucleos(t)ide analogues

DOI: 10.3969/j.issn.1001-5256.2023.05.011
Research funding:

National Science and Technology Key Project on "Major Infectious Diseases such as HIV/AIDS, Viral Hepatitis Prevention and Treatment" (2017ZX10302201-004);

National Science and Technology Key Project on "Major Infectious Diseases such as HIV/AIDS, Viral Hepatitis Prevention and Treatment" (2017ZX10202203-006);

National Science and Technology Key Project on "Major Infectious Diseases such as HIV/AIDS, Viral Hepatitis Prevention and Treatment" (2017ZX10201201);

National Science and Technology Key Project on "Major Infectious Diseases such as HIV/AIDS, Viral Hepatitis Prevention and Treatment" (2017ZX10203201-005)

More Information
  • Corresponding author: ZHENG Sujun, zhengsujun@ccmu.edu.cn (ORCID: 0000-0002-6367-5764)
  • Received Date: 2022-09-23
  • Accepted Date: 2022-12-22
  • Published Date: 2023-05-20
  •   Objective  To investigate the ability of combined baseline serum markers, i.e., HBV DNA, HBV RNA, HBsAg, and HBcrAg, to predict HBeAg seroconversion in patients with HBeAg-positive chronic hepatitis B (CHB) treated by nucleos(t)ide analogues.  Methods  A retrospective analysis was performed for 83 HBeAg-positive patients selected as subjects from the prospective CHB follow-up cohort established by Difficult & Complicated Liver Diseases and Artificial Liver Center, Beijing YouAn Hospital, Capital Medical University, from June 2007 to July 2008, and the baseline serum levels of HBV DNA, HBV RNA, HBsAg, and HBcrAg were analyzed. The t-test or the Mann-Whitney U test was used for comparison of continuous data between two groups, and the chi-square test was used for comparison of categorical data between two groups. The Spearman method was used for correlation analysis. A Cox regression model was established to calculate HBeAg seroconversion prediction score, and the time-dependent receiver operating characteristic curve was used to evaluate the ability of combined markers in predicting HBeAg seroconversion. The Kaplan-Meier method was used to calculate cumulative seroconversion rate in each group, and the Log-rank test was used for comparison between groups.  Results  For the 83 HBeAg-positive patients, the median follow-up time was 108 months, and 44.58%(37/83) of these patients achieved HBeAg seroconversion. Compared with the non-seroconversion group, the HBeAg seroconversion group had significantly lower baseline serum levels of HBV DNA [6.23(1.99-9.28) log10IU/mL vs 7.69(2.05-8.96) log10IU/mL, Z=-2.345, P=0.019] and HBV RNA [4.81(1.40-7.53) log10copies/mL vs 6.22(2.00-8.49) log10copies/mL, Z=-1.702, P=0.010], and there were no significant differences in the levels of HBsAg and HBcrAg between the two groups (P > 0.05). The Cox regression equation constructed based on the above serum markers showed a median score of 0.95(range 0.37-3.45) for predicting HBeAg seroconversion. In the total population, the combined score was negatively correlated with HBsAg, HBV DNA, HBV RNA, and HBcrAg (r=-0.697, -0.787, -0.990, and -0.819, all P < 0.001). Based on the median prediction score, the patients were divided into high HBeAg seroconversion group and low HBeAg seroconversion group; as for the prediction of HBeAg seroconversion rate at 36, 60, and 84 months, the high HBeAg seroconversion group had a seroconversion rate of 43.90%, 51.20%, and 63.10%, respectively, while the low HBeAg seroconversion group had a seroconversion rate of 9.60%, 17.00%, and 19.8%, respectively, and there was a significant difference between the two groups (χ2=11.6, P < 0.001).  Conclusion  The combined prediction score based on baseline serum HBV markers can predict HBeAg seroconversion in CHB patients treated by nucleos(t)ide analogues.

     

  • loading
  • [1]
    REVILL PA, CHISARI FV, BLOCK JM, et al. A global scientific strategy to cure hepatitis B[J]. Lancet Gastroenterol Hepatol, 2019, 4(7): 545-558. DOI: 10.1016/S2468-1253(19)30119-0.
    [2]
    Polaris Observatory Collaborators. Global prevalence, treatment, and prevention of hepatitis B virus infection in 2016: a modelling study[J]. Lancet Gastroenterol Hepatol, 2018, 3(6): 383-403. DOI: 10.1016/S2468-1253(18)30056-6.
    [3]
    ZHOU WW, HUANG J, PAN FM. Research progress in epidemiological characteristics and therapeutic drugs of chronic hepatitis B[J]. J Changchun Univ Chin Med, 2022, 38(12): 1420-1424. DOI: 10.13463/j.cnki.cczyy.2022.12.028.

    周薇薇, 黄俊, 潘发明. 慢性乙型肝炎流行病学特点和治疗药物研究进展[J]. 长春中医药大学学报, 2022, 38(12): 1420-1424. DOI: 10.13463/j.cnki.cczyy.2022.12.028.
    [4]
    LU F, WANG J, CHEN X, et al. Potential use of serum HBV RNA in antiviral therapy for chronic hepatitis B in the era of nucleos(t)ide analogs[J]. Front Med, 2017, 11(4): 502-508. DOI: 10.1007/s11684-017-0590-z.
    [5]
    LI H, XU WT, DENG BC, et al. Progress in the functional treatment of chronic hepatitis B with nucleos(t)ide analogues and pegylated interferon[J]. Clin J Med Offic, 2022, 50(9): 890-893. DOI: 10.16680/j.1671-3826.2022.09.04.

    李卉, 许文涛, 邓宝成, 等. 核苷(酸)类似物联合聚乙二醇干扰素功能性治愈慢性乙型肝炎研究进展[J]. 临床军医杂志, 2022, 50(9): 890-893. DOI: 10.16680/j.1671-3826.2022.09.04.
    [6]
    JANSEN L, KOOTSTRA NA, VAN DORT KA, et al. Hepatitis B virus pregenomic RNA is present in virions in plasma and is associated with a response to pegylated interferon alfa-2a and nucleos(t)ide analogues[J]. J Infect Dis, 2016, 213(2): 224-232. DOI: 10.1093/infdis/jiv397.
    [7]
    van BÖMMEL F, BARTENS A, MYSICKOVA A, et al. Serum hepatitis B virus RNA levels as an early predictor of hepatitis B envelope antigen seroconversion during treatment with polymerase inhibitors[J]. Hepatology, 2015, 61(1): 66-76. DOI: 10.1002/hep.27381.
    [8]
    WANG Y, LIAO H, DENG Z, et al. Serum HBV RNA predicts HBeAg clearance and seroconversion in patients with chronic hepatitis B treated with nucleos(t)ide analogues[J]. J Viral Hepat, 2022, 29(6): 420-431. DOI: 10.1111/jvh.13671.
    [9]
    WANG B, CAREY I, BRUCE M, et al. HBsAg and HBcrAg as predictors of HBeAg seroconversion in HBeAg-positive patients treated with nucleos(t)ide analogues[J]. J Viral Hepat, 2018, 25(8): 886-893. DOI: 10.1111/jvh.12889.
    [10]
    LUO H, ZHANG XX, CAO LH, et al. Serum hepatitis B virus RNA is a predictor of HBeAg seroconversion and virological response with entecavir treatment in chronic hepatitis B patients[J]. World J Gastroenterol, 2019, 25(6): 719-728. DOI: 10.3748/wjg.v25.i6.719.
    [11]
    Chinese Society of Hepatology and Chinese Society of Infectious Diseases, Chinese Medical Association. Guidelines for the prevention and treatment of chronic hepatitis B[J]. J Clin Hepatol, 2006, 22(1): 3-15. DOI: 10.3969/j.issn.1001-5256.2006.01.001.

    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[J]. 临床肝胆病杂志, 2006, 22(1): 3-15. DOI: 10.3969/j.issn.1001-5256.2006.01.001.
    [12]
    LIAO H, LIU Y, LI X, et al. Monitoring of serum HBV RNA, HBcrAg, HBsAg and anti-HBc levels in patients during long-term nucleoside/nucleotide analogue therapy[J]. Antivir Ther, 2019, 24(2): 105-115. DOI: 10.3851/IMP3280.
    [13]
    WANG J, SHEN T, HUANG X, et al. Serum hepatitis B virus RNA is encapsidated pregenome RNA that may be associated with persistence of viral infection and rebound[J]. J Hepatol, 2016, 65(4): 700-710. DOI: 10.1016/j.jhep.2016.05.029.
    [14]
    HUANG H, WANG J, LI W, et al. Serum HBV DNA plus RNA shows superiority in reflecting the activity of intrahepatic cccDNA in treatment-naçve HBV-infected individuals[J]. J Clin Virol, 2018, 99-100: 71-78. DOI: 10.1016/j.jcv.2017.12.016.
    [15]
    WANG J, YU Y, LI G, et al. Relationship between serum HBV-RNA levels and intrahepatic viral as well as histologic activity markers in entecavir-treated patients[J]. J Hepatol, 2018, 68(1): 16-24. DOI: 10.1016/j.jhep.2017.08.021.
    [16]
    HATAKEYAMA T, NOGUCHI C, HIRAGA N, et al. Serum HBV RNA is a predictor of early emergence of the YMDD mutant in patients treated with lamivudine[J]. Hepatology, 2007, 45(5): 1179-1186. DOI: 10.1002/hep.21581.
    [17]
    FAN R, ZHOU B, XU M, et al. Association between negative results from tests for HBV DNA and RNA and durability of response after discontinuation of nucles(t)ide analogue therapy[J]. Clin Gastroenterol Hepatol, 2020, 18(3): 719-727. DOI: 10.1016/j.cgh.2019.07.046.
    [18]
    WANG X, WANG Z, CHI X, et al. Efficacy of a combination of HBV RNA and HBeAg in predicting HBeAg seroconversion in patients treated with entecavir for 144 weeks[J]. Int J Infect Dis, 2020, 99: 171-178. DOI: 10.1016/j.ijid.2020.07.031.
    [19]
    CHEN EQ, WANG ML, TAO YC, et al. Serum HBcrAg is better than HBV RNA and HBsAg in reflecting intrahepatic covalently closed circular DNA[J]. J Viral Hepat, 2019, 26(5): 586-595. DOI: 10.1111/jvh.13061.
    [20]
    WANG J, DU M, HUANG H, et al. Reply to: "Serum HBV pgRNA as a clinical marker for cccDNA activity": Consistent loss of serum HBV RNA might predict the "para-functional cure" of chronic hepatitis B[J]. J Hepatol, 2017, 66(2): 462-463. DOI: 10.1016/j.jhep.2016.10.034.
    [21]
    BROUWER WP, XIE Q, SONNEVELD MJ, et al. Adding pegylated interferon to entecavir for hepatitis B e antigen-positive chronic hepatitis B: A multicenter randomized trial (ARES study)[J]. Hepatology, 2015, 61(5): 1512-1522. DOI: 10.1002/hep.27586.
    [22]
    CHI H, HANSEN BE, GUO S, et al. Pegylated interferon alfa-2b add-on treatment in hepatitis B virus envelope antigen-positive chronic hepatitis B patients treated with nucleos(t)ide analogue: a randomized, controlled trial (PEGON)[J]. J Infect Dis, 2017, 215(7): 1085-1093. DOI: 10.1093/infdis/jix024.
  • 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(2)

    Article Metrics

    Article views (413) PDF downloads(102) Cited by()
    Proportional views
    Related

    /

    DownLoad:  Full-Size Img  PowerPoint
    Return
    Return