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ISSN 2097-3497 (Online)
CN 22-1108/R
Volume 41 Issue 8
Aug.  2025
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Article Navigation >  Journal of Clinical Hepatology  > 2025  >  41(8): 1525-1532

Analysis of influencing factors and construction of predictive model for HBsAg clearance in patients with HBeAg-negative chronic hepatitis B treated with PEG-IFN-α-2b

DOI: 10.12449/JCH250810
  • 1.

    Yunnan Infectious Disease Clinical Medical Center，Kunming Third People’s Hospital，Kunming 650041，China

  • 2.

    School of Public Health，Dali University，Dali，Yunnan 671000，China

Research funding:

Yunnan Province Science and Technology Plan Project (2017FH001-088)

More Information
  • Corresponding author: MOU Chunyan， 784652835@qq.com （ORCID： 0009-0000-7301-3302）; LIU Li， liuli197210@163.com （ORCID： 0000-0001-7712-4931）
  • Accepted Date: 2025-01-21
  • Published Date: 2025-08-25
    Abstract
  •   Objective  To investigate the predictive factors for the occurrence of HBsAg clearance in patients with HBeAg-negative chronic hepatitis B （CHB） receiving peginterferon alfa-2b （PEG-IFN-α-2b） treatment， analyze the effects of various indicators on the HBsAg clearance rate under different characteristics， and construct and evaluate a combined predictive model.  Methods  We included 125 patients with HBeAg-negative CHB at Kunming Third People’s Hospital from May 2021 to May 2023. After treatment with PEG-IFN-α-2b combined with nucleoside analogues for a course of 48 weeks， they were divided into HBsAg clearance group and HBsAg non-clearance group. Their general information and serological， biochemical， and virological indicators at different time points during treatment were recorded. Continuous data in normal distribution were compared using the t test. Continuous data in non-normal distribution were compared using the Mann-Whitney U test， and comparisons across different time points were performed using the multiple paired-sample Friedman test. Categorical data were compared using the χ2 test. A Logistic regression analysis was used to select variables to establish a combined multi-parameter predictive model. Receiver operating characteristic （ROC） curves were generated to evaluate the diagnostic value of individual indicators and the combined predictive model for HBsAg clearance.  Results  Before treatment， there were significant differences in baseline HBsAg level （Z=-3.997，P<0.05） and treatment history （χ2=8.221，P<0.05） between the two groups. During treatment， gradually decreasing trends were observed in white blood cell count （χ2=104.944）， neutrophil count （χ2=132.036）， platelet count （χ2=162.881）， and thyroid-stimulating hormone level （TSH，χ2=83.304，all P<0.05）， while alanine aminotransferase （ALT，χ2=157.618） and alpha fetoprotein （χ2=159.472） showed gradually increasing trends （both P<0.05）. At 48 weeks of treatment， treatment history （odds ratio ［OR］=0.232， 95% confidence interval ［CI］：0.071‍‍ — ‍‍‍ ‍0.753）， baseline HBsAg level （OR=13.423，95%CI：3.276‍ — ‍‍54.997）， the extent of decrease in HBsAg from baseline after 12 weeks of treatment （OR=0.143，95%CI：0.040‍ ‍— ‍‍‍ ‍0.515）， the maximum ALT level during treatment （OR=0.986，95%CI：0.980‍ — ‍‍0.993）， and the minimum TSH level during treatment （OR=3.281，95%CI：1.413‍‍‍ ‍— ‍‍‍7.619） were independent factors affecting HBsAg clearance （all P<0.05）. A combined predictive model for HBsAg clearance was built：Y=-1.603-1.462×treatment history+2.597×baseline HBsAg value-1.944×the extent of HBsAg reduction from baseline after 12 weeks of treatment-0.014×the maximum ALT value during treatment+1.188×the minimum TSH value during treatment. The diagnostic value of the individual indicators for HBsAg clearance from high to low was as following： the maximum ALT value during treatment （AUC=0.824）， baseline HBsAg value （AUC=0.727）， the minimum TSH value during treatment （AUC=0.707）， the extent of HBsAg reduction from baseline after 12 weeks of treatment （AUC=0.641）， and treatment history （AUC=0.636）. The combined model showed better predictive performance than the individual indicators， with the AUC being 0.921 （all P<0.05）.  Conclusion  The combined model， constructed with baseline HBsAg value， the extent of HBsAg reduction from baseline after 12 weeks of treatment， the maximum ALT value during treatment， and the minimum TSH value during treatment， has high predictive value for the occurrence of HBsAg clearance in patients with HBeAg-negative CHB after 48 weeks of treatment with PEG-IFN-α-2b， which can provide a reference for identifying suitable patients for treatment and predicting clinical outcome.

     

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    • References(24)
  • [1]
    YANG XA, ZHANG K, XU QH, et al. Interferon add-on therapy increased clinical cure significantly for interferon-experienced chronic hepatitis B patients with low HBsAg[J]. Front Immunol, 2022, 13: 997608. DOI: 10.3389/fimmu.2022.997608.
    [2]
    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.
    [3]
    Chinese Society of Hepatology, Chinese Medical Association, Chinese Society of Infectious Diseases, Chinese Medical Association. Guidelines for the prevention and treatment of chronic hepatitis B(version 2022)[J]. J Prac Hepatol, 2023, 26( 3): Suppl. 1- 22. DOI: 10.3969/j.issn.1672-5069.2023.040.

    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(2022年版)[J]. 实用肝脏病杂志, 2023, 26( 3): 后插1-后插 22. DOI: 10.3969/j.issn.1672-5069.2023.03.040.
    [4]
    OGUNNAIKE M, DAS S, RAUT SS, et al. Chronic hepatitis B infection: New approaches towards cure[J]. Biomolecules, 2023, 13( 8): 1208. DOI: 10.3390/biom13081208.
    [5]
    YAN Y, CHANTSALMAA D, LYU CY, et al. Predictive value of baseline serum marker levels for the effect of interferon therapy in patients with chronic hepatitis B[J]. J Sichuan Univ Med Sci, 2024, 55( 2): 383- 390. DOI: 10.12182/20240360105.

    阎岩, Chantsalmaa Davgadorj, 吕春燕, 等. 慢性乙型肝炎患者的血清标志物基线水平对干扰素治疗效果的预测价值[J]. 四川大学学报(医学版), 2024, 55( 2): 383- 390. DOI: 10.12182/20240360105.
    [6]
    ZHANG WH, ZHANG DZ, DOU XG, et al. 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.
    [7]
    LI YP, LIU CR, HE L, et al. Hepatitis B cure: Current situation and prospects[J]. World J Hepatol, 2024, 16( 6): 900- 911. DOI: 10.4254/wjh.v16.i6.900.
    [8]
    FARAG MS, van CAMPENHOUT MJH, SONNEVELD MJ, et al. Addition of PEG-interferon to long-term nucleos(t)ide analogue therapy enhances HBsAg decline and clearance in HBeAg-negative chronic hepatitis B: Multicentre Randomized Trial(PAS Study)[J]. J Viral Hepat, 2024, 31( 4): 197- 207. DOI: 10.1111/jvh.13918.
    [9]
    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.
    [10]
    LI K, NING HB, JIN HM, et al. Effect of pegylated interferon α-2b on serum HBsAg clearance rate in treatment of patients with chronic hepatitis B[J]. J Clin Hepatol, 2023, 39( 8): 1819- 1824. DOI: 10.3969/j.issn.1001-5256.2023.08.009.

    李宽, 宁会彬, 靳慧鸣, 等. 聚乙二醇干扰素α-2b治疗慢性乙型肝炎患者血清HBsAg清除率的效果分析[J]. 临床肝胆病杂志, 2023, 39( 8): 1819- 1824. DOI: 10.3969/j.issn.1001-5256.2023.08.009.
    [11]
    WANG JL, XI DY, YAN XB, et al. Predictors of HBsAg clearance in HBeAg-negative chronic hepatitis B patients treated with pegylated interferon α-2b and the construction of a nomogram model[J]. J Clin Hepatol, 2023, 39( 12): 2809- 2816. DOI: 10.3969/j.issn.1001-5256.2023.12.010.

    王佳露, 席德扬, 颜学兵, 等. 聚乙二醇干扰素α-2b治疗HBeAg阴性慢性乙型肝炎患者实现HBsAg清除的预测因素及列线图构建[J]. 临床肝胆病杂志, 2023, 39( 12): 2809- 2816. DOI: 10.3969/j.issn.1001-5256.2023.12.010.
    [12]
    ZANG HY, LI WN, LIU SS, et al. Predictive factors for functional cure after sequential therapy with nucleos(t)ide analogues and pegylated interferon Alfa-2b in treatment of chronic hepatitis B[J]. J Clin Hepatol, 2023, 39( 2): 299- 306. DOI: 10.3969/j.issn.1001-5256.2023.02.008.

    臧海洋, 李伟娜, 刘守胜, 等. 核苷(酸)类似物序贯派格宾治疗慢性乙型肝炎实现功能性治愈的预测因素[J]. 临床肝胆病杂志, 2023, 39( 2): 299- 306. DOI: 10.3969/j.issn.1001-5256.2023.02.008.
    [13]
    HE XJ, LONG YZ, ZHOU J, et al. Serum hepatitis B virus RNA monitoring pegylated interferon therapy nucleos(t) ide analogues in the treatment of low viral load in patients with chronic hepatitis B curative effect[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.
    [14]
    LI YY, YANG SQ, LI C, et al. Efficacy of short-term Peg-IFN α-2b treatment in chronic hepatitis B patients with ultra-low HBsAg levels: A retrospective cohort study[J]. Virol J, 2024, 21( 1): 231. DOI: 10.1186/s12985-024-02512-w. DOI: 10.3969/j.issn.1001-5256.2023.02.008.
    [15]
    ZHONG WT, YAN LZ, ZHU YG, et al. A high functional cure rate was induced by pegylated interferon alpha-2b treatment in postpartum hepatitis B e antigen-negative women with chronic hepatitis B virus infection: An exploratory study[J]. Front Cell Infect Microbiol, 2024, 14: 1426960. DOI: 10.3389/fcimb.2024.1426960.
    [16]
    IANNAZZO S, COCO B, BRUNETTO MR, et al. Individualized treatment of HBeAg-negative chronic hepatitis B using pegylated interferon-α2a as first-line and week-12 HBV DNA/HBsAg stopping rule: A cost-effectiveness analysis[J]. Antivir Ther, 2013, 18( 4): 623- 633. DOI: 10.3851/IMP2555.
    [17]
    GU LL, HU R, DOU YM, et al. Predictors associated with functional cure in HBeAg-negative chronic hepatitis B patients treated with pegylated interferon α-2b[J]. Chin Hepatol, 2023, 28( 3): 313- 319. DOI: 10.14000/j.cnki.issn.1008-1704.2023.03.014.

    顾琳琳, 胡瑞, 窦宇明, 等. 聚乙二醇干扰素α-2b治疗HBeAg阴性慢性乙型肝炎实现临床治愈的预测因素分析[J]. 肝脏, 2023, 28( 3): 313- 319. DOI: 10.14000/j.cnki.issn.1008-1704.2023.03.014.
    [18]
    WONG D, LITTLEJOHN M, EDWARDS R, et al. ALT flares during nucleotide analogue therapy are associated with HBsAg loss in genotype A HBeAg-positive chronic hepatitis B[J]. Liver Int, 2018, 38( 10): 1760- 1769. DOI: 10.1111/liv.13716.
    [19]
    CHIEN RN, LIAW YF. Re-treatment for severe hepatitis flare in HBeAg-negative chronic hepatitis B: An appraisal with combined HBsAg/ALT kinetics[J]. J Viral Hepat, 2020, 27( 5): 544- 547. DOI: 10.1111/jvh.13253.
    [20]
    WU LL, GAO ZL. Predictive factors for HBsAg-negative seroconversion in chronic hepatitis B after antiviral therapy[J]. Chin J Hepatol, 2024, 32( 2): 186- 192. DOI: 10.3760/cm3.j.cn501113-20231213-00278.

    吴丽丽, 高志良. 抗病毒治疗后慢性乙型肝炎HBsAg阴转的预测因子[J]. 中华肝脏病杂志, 2024, 32( 2): 186- 192. DOI: 10.3760/cma.j.cn501113-20231213-00278.
    [21]
    TANG QQ, YE J, ZHANG YF, et al. Establishment of a multi-parameter prediction model for the functional cure of HBeAg-negative chronic hepatitis B patients treated with pegylated interferonα and decision process based on response-guided therapy strategy[J]. BMC Infect Dis, 2023, 23( 1): 456. DOI: 10.1186/s12879-023-08443-1.
    [22]
    MA ZX, QIN YL, JIA YD, et al. Thyroid dysfunction incidence and risk factors in Chinese chronic hepatitis B patients treated with pegylated interferon alpha: A long-term follow-up study[J]. J Viral Hepat, 2022, 29( 6): 412- 419. DOI: 10.1111/jvh.13667.
    [23]
    HUANG FT, LIN YM, RAO KM, et al. Effect of a—interferon in treating chronic hepatitis B on liver function,hepatitis B surface antigen and thyroid function[J]. Lab Med Clin, 2024, 21( 19): 2920- 2924. DOI: 10.3969/j.issn.1672-9455.2024.19.0274.

    皇甫彤, 蔺咏梅, 饶珂萌, 等. α-干扰素治疗慢性乙型肝炎对患者肝功能、乙型肝炎表面抗原及甲状腺功能的影响[J]. 检验医学与临床, 2024, 21( 19): 2920- 2924. DOI: 10.3969/j.issn.1672-9455.2024.19.0274.
    [24]
    MU H, XU DQ, LIU CY, et al. Relationship between HBsAg and TSH during interferon treatment in hepatitis B patients with low HBsAg level[J]. Chongqing Med J, 2024, 53( 18): 2826- 2829. DOI: 10.3969/j.issn.1671-8348.2024.18.020.

    木唤, 许丹青, 刘春云, 等. 低HBsAg水平乙型肝炎患者使用干扰素治疗期间HBsAg与TSH的关系[J]. 重庆医学, 2024, 53( 18): 2826- 2829. DOI: 10.3969/j.issn.1671-8348.2024.18.020.
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