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Volume 41 Issue 7
Jul.  2025
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Article Navigation >  Journal of Clinical Hepatology  > 2025  >  41(7): 1313-1318

Changing trend of serum tumor necrosis factor-alpha level during pegylated interferon-alpha treatment in inactive HBsAg carriers and its association with HBsAg clearance

DOI: 10.12449/JCH250714

  • Department of Infectious Diseases，The Second Affiliated Hospital of Xi’an Jiaotong University，Xi’an 710004，China

Research funding:

Youth Program of the Shaanxi Provincial Natural Science Basic Research Program (2024JC-YBQN-0928);

Fund of the Second Affiliated Hospital of Xi’an Jiaotong University (YJ（QN）202309);

IIT Clinical Research Fund of the Second Affiliated Hospital of Xi’an Jiaotong University (M094)

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  • Corresponding author: DANG Shuangsuo， dang212@126.com （ORCID： 0000-0003-0918-9535）
  • Received Date: 2024-11-05
  • Accepted Date: 2025-04-14
  • Published Date: 2025-07-25
    Abstract
  •   Objective  To observe the changes in the serum level of tumor necrosis factor-α （TNF-α） during pegylated interferon-alpha （PEG-IFN-α） treatment in inactive HBsAg carriers （IHCs）， to investigate the association between the dynamic changes of TNF-α and HBsAg clearance， and to assess the value of TNF-α as a potential biomarker for predicting the therapeutic efficacy of PEG-IFN-α.  Methods  A prospective study was conducted among 455 IHCs who attended our hospital from January 2018 to March 2023， and they were divided into treatment group and IHC control group. The 210 IHCs in the treatment group voluntarily received PEG-IFNα-2b treatment for 48 weeks， followed by follow-up for 24 weeks， and the 245 IHCs in the IHC control group were followed up for 72 weeks without treatment. The serum level of TNF-α was measured at baseline （week 0） and at weeks 12， 24，48， and 72， and at week 72， the treatment group was further divided into HBsAg clearance group and non-clearance group. The serum level of TNF-α at different time points was compared between groups. The logistic regression analysis was used to assess the value of TNF-α in predicting HBsAg clearance. The t-test was used for comparison of normally distributed continuous data between two groups， and a one-way analysis of variance used for comparison between multiple groups； the repeated measures analysis of variance was used for comparison of normally distributed repeated measurement data within each group and between groups； the chi-square test or the Fisher’s exact test was used for comparison of categorical data between groups. Univariate and multivariate logistic regression analyses were used to investigate the predictive factors for HBsAg clearance， and the receiver operating characteristic （ROC） curve was used to determine the cut-off value of TNF-α in predicting HBsAg clearance.  Results  At week 72， compared with the IHC control group， the treatment group had significantly higher HBsAg clearance rate （46.2% vs 1.2%， χ2=133.333，P<0.001） and seroconversion rate （34.8% vs 0.8%， χ2=94.650，P<0.001）. The HBsAg clearance group and the non-clearance group had a significant increase in the serum level of TNF-α during treatment， which gradually returned to the baseline level after drug withdrawal （F=351.733 and 76.434， both P<0.001）. Comparisons between groups showed that the HBsAg clearance group had the highest serum level of TNF-α at weeks 12， 24， and 48， followed by the non-clearance group and the IHC control group （all P<0.001）. The multivariate logistic regression analysis showed that baseline HBsAg level （odds ratio ［OR］=0.329，95% confidence interval ［CI］：0.189‍ ‍—‍ ‍0.571，P<0.001）， baseline HBV DNA <20 IU/mL （OR=1.414，95%CI：1.057‍ ‍—‍ ‍1.787，P=0.045）， ALT≥2×upper limit of normal at week 12 （OR=1.127，95%CI：1.028‍ ‍—‍ ‍1.722，P=0.043）， TNF-α level at week 12 （OR=1.336，95%CI：1.018‍ ‍—‍ ‍1.754，P=0.037）， and TNF-α level at week 24 （OR=1.879，95%CI：1.477‍ ‍—‍ ‍2.391，P<0.001） were independent predictive factors for HBsAg clearance. The ROC analysis showed that TNF-α level at week 12 had an area under the ROC curve （AUC） of 0.846 （95%CI：0.814‍ ‍—‍ ‍0.889） in predicting HBsAg clearance at week 72， with a sensitivity of 76.3% and a specificity of 81.0%， while TNF-α level at week 24 had an AUC of 0.912 （95%CI：0.758‍ ‍—‍ ‍0.972）， with a sensitivity of 81.4% and a specificity of 96.2%.  Conclusion  PEG-IFN-α can increase the serum level of TNF-α in IHCs， and the serum level of TNF-α at weeks 12 and 24 can effectively predict HBsAg clearance induced by PEG-IFN-α.

     

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    • References(14)
  • [1]
    YAO KF, LIU JC, WANG J, et al. Distribution and clinical characteristics of patients with chronic hepatitis B virus infection in the grey zone[J]. J Viral Hepat, 2021, 28( 7): 1025- 1033. DOI: 10.1111/jvh.13511.
    [2]
    INVERNIZZI F, VIGANÒ M, GROSSI G, et al. The prognosis and management of inactive HBV carriers[J]. Liver Int, 2016, 36( S1): 100- 104. DOI: 10.1111/liv.13006.
    [3]
    YOU H, WANG FS, LI TS, et al. Guidelines for the prevention and treatment of chronic hepatitis B(version 2022)[J]. J Clin Transl Hepatol, 2023, 11( 6): 1425- 1442. DOI: 10.14218/JCTH.2023.00320.
    [4]
    WU FP, LU R, LIU YX, et al. Efficacy and safety of peginterferon alpha monotherapy in Chinese inactive chronic hepatitis B virus carriers[J]. Liver Int, 2021, 41( 9): 2032- 2045. DOI: 10.1111/liv.14897.
    [5]
    WONG GLH, GANE E, LOK ASF. How to achieve functional cure of HBV: Stopping NUCs, adding interferon or new drug development?[J]. J Hepatol, 2022, 76( 6): 1249- 1262. DOI: 10.1016/j.jhep.2021.11.024.
    [6]
    HE XJ, LONG YZ, ZHOU J, et al. Monitoring serum hepatitis B virus RNA to assess the efficacy of pegylated interferon therapy in nucleos(t)ide analog-experienced chronic hepatitis B patients with low viral load[J]. Clin J Med Offic, 2023, 51( 10): 1091- 1095. DOI: 10.16680/j.1671-3826.2023.10.27.

    贺潇瑾, 龙云铸, 周娟, 等. 血清乙型肝炎病毒RNA监测聚乙二醇干扰素治疗核苷(酸)类似物经治低病毒载量慢性乙型肝炎患者疗效[J]. 临床军医杂志, 2023, 51( 10): 1091- 1095. DOI: 10.16680/j.1671-3826.2023.10.27.
    [7]
    XIAO LX, TANG K, FU T, et al. Cytokine profiles and virological markers highlight distinctive immune statuses, and effectivenesses and limitations of NAs across different courses of chronic HBV infection[J]. Cytokine, 2024, 173: 156442. DOI: 10.1016/j.cyto.2023.156442.
    [8]
    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.
    [9]
    CAO ZH, LIU YL, MA LN, et al. A potent hepatitis B surface antigen response in subjects with inactive hepatitis B surface antigen carrier treated with pegylated-interferon alpha[J]. Hepatology, 2017, 66( 4): 1058- 1066. DOI: 10.1002/hep.29213.
    [10]
    ZENG QL, YU ZJ, SHANG J, et al. Short-term peginterferon-induced high functional cure rate in inactive chronic hepatitis B virus carriers with low surface antigen levels[J]. Open Forum Infect Dis, 2020, 7( 6): ofaa208. DOI: 10.1093/ofid/ofaa208.
    [11]
    WU FP, WANG YK, CUI D, et al. Short-term peg-IFN alpha-2b re-treatment induced a high functional cure rate in patients with HBsAg recurrence after stopping PEG-IFN alpha-based regimens[J]. J Clin Med, 2023, 12( 1): 361. DOI: 10.3390/jcm12010361.
    [12]
    BEKCIBASI M, DEVECI O, OGUZ A, et al. Serum TNF-alpha, IL-1beta, and IL-6 levels in chronic HBV-infected patients[J]. Int J Clin Pract, 2021, 75( 8): e14292. DOI: 10.1111/ijcp.14292.
    [13]
    LE BERT N, GILL US, HONG M, et al. Effects of hepatitis B surface antigen on virus-specific and global T cells in patients with chronic hepatitis B virus infection[J]. Gastroenterology, 2020, 159( 2): 652- 664. DOI: 10.1053/j.gastro.2020.04.019.
    [14]
    WU FP, YANG Y, LI M, et al. Add-on pegylated interferon augments hepatitis B surface antigen clearance vs continuous nucleos(t)ide analog monotherapy in Chinese patients with chronic hepatitis B and hepatitis B surface antigen≤1 500 IU/mL: An observational study[J]. World J Gastroenterol, 2020, 26( 13): 1525- 1539. DOI: 10.3748/wjg.v26.i13.1525.
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