中文English
ISSN 1001-5256
CN 22-1108/R

留言板

尊敬的读者、作者、审稿人, 关于本刊的投稿、审稿、编辑和出版的任何问题, 您可以本页添加留言。我们将尽快给您答复。谢谢您的支持!

姓名
邮箱
手机号码
标题
留言内容
验证码

加用干扰素治疗核苷(酸)类似物经治的HBsAg低水平的慢性乙型肝炎患者获得临床治愈的效果观察

牛卫理 王永素 吴清山 张林 张中琴 杨小军 朱先彬 肖文琴 纪明平

牛卫理,王永素,吴清山,等. 加用干扰素治疗核苷(酸)类似物经治的HBsAg低水平的慢性乙型肝炎患者获得临床治愈的效果观察[J]. 临床肝胆病杂志, 2021, 37(8): 1793-1797. DOI: 10.3969/j.issn.1001-5256.2021.08.010
引用本文: 牛卫理,王永素,吴清山,等. 加用干扰素治疗核苷(酸)类似物经治的HBsAg低水平的慢性乙型肝炎患者获得临床治愈的效果观察[J]. 临床肝胆病杂志, 2021, 37(8): 1793-1797. DOI: 10.3969/j.issn.1001-5256.2021.08.010
NIU WL, WANG YS, WU QS, et al. A clinical study of clinical cure after the addition of interferon therapy in chronic hepatitis B patients with low-level HBsAg previously treated with nucleos(t)ide analogues[J]. J Clin Hepatol, 2021, 37(8): 1793-1797. DOI: 10.3969/j.issn.1001-5256.2021.08.010
Citation: NIU WL, WANG YS, WU QS, et al. A clinical study of clinical cure after the addition of interferon therapy in chronic hepatitis B patients with low-level HBsAg previously treated with nucleos(t)ide analogues[J]. J Clin Hepatol, 2021, 37(8): 1793-1797. DOI: 10.3969/j.issn.1001-5256.2021.08.010

加用干扰素治疗核苷(酸)类似物经治的HBsAg低水平的慢性乙型肝炎患者获得临床治愈的效果观察

DOI: 10.3969/j.issn.1001-5256.2021.08.010
基金项目: 

佑安肝病感染病专科医疗联盟科研专项 LM202010

北京医卫健康公益基金会医学科学研究基金资助项目 YWJKJJHKYJJ-B17715

详细信息
    通讯作者:

    牛卫理,nwl_0082004@sina.com

  • 中图分类号: R512.62

A clinical study of clinical cure after the addition of interferon therapy in chronic hepatitis B patients with low-level HBsAg previously treated with nucleos(t)ide analogues

Funds: 

Special Research Fund of YouAn Medical Alliance for the Liver and Infectious Diseases LM202010

Medical Science Research Fund Project of Beijing Medical and Health Foundation YWJKJJHKYJJ-B17715

  • 摘要:   目的  探讨核苷(酸)类似物(NAs)经治的慢性乙型肝炎患者获得临床治愈的优势人群,为临床医生追求乙型肝炎临床治愈提供更多的方法。  方法  选取2017年10月—2019年10月在鹤壁市第三人民医院接受NAs治疗且HBsAg低水平的慢性乙型肝炎患者42例作为研究对象,分为联合治疗组(A组, n=22)和NAs单药治疗组(B组, n=20)。A组采用NAs联合聚乙二醇干扰素(PEG-IFN)抗病毒治疗48周,部分患者24周停用PEG-IFN继续NAs单药治疗。B组仅采用NAs抗病毒治疗,两组均观察至48周,通过乙型肝炎五项定量检测评估疗效。计量资料两组间比较采用t检验;计数资料两组间比较采用Fisher精确检验。影响因素相关分析采用logistic回归法。  结果  48周治疗终点A组的HBsAg清除率(45.5%)和HBsAg血清学转换率(31.8%)远高于B组(均为0)(P值均<0.01);HBsAg<1000 IU/ml、<500 IU/ml、<100 IU/ml、<10 IU/ml人群的HBsAg清除率分别为52.6%、61.5%、66.7%和100%;HBsAg在500~1000 IU/ml、100~500 IU/ml、10~100 IU/ml、<10 IU/ml区间人群的HBsAg清除率分别为33.3%、50%、40%和100%。4例基线HBsAg<10 IU/ml者(占联合治疗组18.2%),联合治疗12周取得临床治愈,观察至48周时2例抗-HBs>100 IU/ml,2例抗-HBs>1000 IU/ml。HBsAg清除的多因素logsitic回归分析结果显示:开始联合治疗时的年龄对HBsAg清除存在影响(OR=0.877,95%CI:0.781~0.985,P=0.026),HBsAg阴转患者的年龄集中在36~49(44.20±4.49)岁;基线HBsAg水平也对HBsAg清除存在影响(OR=0.996,95%CI:0.992~1.000,P=0.050)。  结论  加用IFN治疗核苷(酸)类似物经治的HBsAg低水平的慢性乙型肝炎患者能够显著提高临床治愈率,年龄越小、HBsAg水平越低,联合治疗时间越短,相较于NAs用药时间、种类,年龄和基线HBsAg水平更关键。

     

  • 表  1  基线时两组患者的临床资料对比

    组别 例数 年龄
    (岁)
    男性
    [例(%)]
    BMI
    (kg/m2)
    NAs治疗时间
    (年)
    HBsAg
    (log10 IU/ml)
    总体 42 47.43±7.10 35(83.33) 25.20±3.01 5.91±3.17 2.12±0.93
    A组 22 44.82±6.20 19(86.36) 24.69±3.33 5.72±4.00 2.02±1.06
    B组 20 47.70±5.11 16(80.00) 25.39±2.66 6.10±1.97 2.23±0.78
    统计值 t=-1.634 t=-0.746 t=-0.388 t=-0.744
    P 0.110 0.691 0.460 0.701 0.462
    下载: 导出CSV

    表  2  两组不同时间节点临床治愈结果比较

    组别 例数 24周 48周
    HBsAg清除[例(%)] 抗-HBs阳性[例(%)] HBsAg清除[例(%)] 抗-HBs阳性[例(%)]
    A组 22 6(27.3) 5(22.7) 10(45.5) 7(31.8)
    B组 20 0 0 0 0
    P 0.022 0.049 0.001 0.009
    下载: 导出CSV

    表  3  联合治疗基线值不同HBsAg定量节点的患者在12、24和48周获得临床治愈率比较

    HBsAg节点 例数 12周治愈率 24周治愈率 48周治愈率
     <1000 IU/ml 19 26.3%(5/19) 31.6%(6/19) 52.6%(10/19)
     <500 IU/ml 13 38.5%(5/13) 46.2%(6/13) 61.5%(8/13)
     <100 IU/ml 9 55.6%(5/9) 55.6%(5/9) 66.7%(6/9)
     <10 IU/ml 4 100%(4/4) 100%(4/4) 100%(4/4)
    下载: 导出CSV

    表  4  联合治疗基线值不同HBsAg定量区间的患者在12、24和48周获得临床治愈率比较

    HBsAg区间 例数 12周治愈率 24周治愈率 48周治愈率
    500~1000 IU/ml 6 0(0/6) 0(0/6) 33.3%(2/6)
    100~500 IU/ml 4 0(0/4) 25.0%(1/4) 50.0%(2/4)
    10~100 IU/ml 5 20.0%(1/5) 20.0%(1/5) 40.0%(2/5)
    <10 IU/ml 4 100%(4/4) 100%(4/4) 100%(4/4)
    下载: 导出CSV
  • [1] 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.
    [2] 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.
    [3] MARCELLIN P, HEATHCOTE EJ, BUTI M, et al. Tenofovir disoproxil fumarate versus adefovir dipivoxil for chronic hepatitis B[J]. N Engl J Med, 2008, 359(23): 2442-2455. DOI: 10.1056/NEJMoa0802878.
    [4] GAO ZL. Hot and difficult points of functional cure (clinical cure) of chronic hepatitis B[J]. Mod Digest Interv, 2019, 24(9): 949-951. DOI: 10.3969/j.issn.1672-2159.2019.09.001.

    高志良. 慢性乙型肝炎功能性治愈(临床治愈)的热点和难点[J]. 现代消化及介入诊疗, 2019, 24(9): 949-951. DOI: 10.3969/j.issn.1672-2159.2019.09.001.
    [5] 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.
    [6] WU Y, LIU Y, LU J, et al. Durability of interferon-induced hepatitis B surface antigen seroclearance[J]. Clin Gastroenterol Hepatol, 2020, 18(2): 514-516.e2. DOI: 10.1016/j.cgh.2019.04.020.
    [7] MARCELIN P, FLISIAK R, TRINH H, et al. Long term treatment with tenofbvir disoproxil fumarate for chronic hepatitis B infection is safe and well tolerated and associated with durable virologic response with no detectable resistance: 8 year results from two phase 3 trials[J]. Hepatol, 2014, 60: 313a-314a. DOI: 10.1002/hep.27059.
    [8] LAMPERTICO P, VIGANÒ M, DI COSTANZO GG, et al. Randomised study comparing 48 and 96 weeks peginterferon α-2a therapy in genotype D HBeAg-negative chronic hepatitis B[J]. Gut, 2013, 62(2): 290-298. DOI: 10.1136/gutjnl-2011-301430.
    [9] CHELBI-ALIX MK, WIETZERBIN J. Interferon, a growing cytokine family: 50 years of interferon research[J]. Biochimie, 2007, 89(6-7): 713-718. DOI: 10.1016/j.biochi.2007.05.001.
    [10] ZHANG S, SUN J, XING HC. Progress on clinical cure of chronic hepatitis B[J/CD]. Chin J Liver Dis (Electronic Version), 2018, 10(4): 54-58. DOI: 10.3969/j.issn.1674-7380.2018.04.009.

    张珊, 孙静, 邢卉春. 慢性乙型肝炎临床治愈研究进展[J/CD]. 中国肝脏病杂志(电子版), 2018, 10(4): 54-58. DOI: 10.3969/j.issn.1674-7380.2018.04.009.
    [11] HAGIWARA S, NISHIDA N, KUDO M. Antiviral therapy for chronic hepatitis B: Combination of nucleoside analogs and interferon[J]. World J Hepatol, 2015, 7(23): 2427-2431. DOI: 10.4254/wjh.v7.i23.2427.
    [12] TAN AT, HOANG LT, CHIN D, et al. Reduction of HBV replication prolongs the early immunological response to IFNα therapy[J]. J Hepatol, 2014, 60(1): 54-61. DOI: 10.1016/j.jhep.2013.08.020.
    [13] NING Q, HAN M, SUN Y, et al. Switching from entecavir to PegIFN alfa-2a in patients with HBeAg-positive chronic hepatitis B: A randomised open-label trial (OSST trial)[J]. J Hepatol, 2014, 61(4): 777-784. DOI: 10.1016/j.jhep.2014.05.044.
    [14] HU P, SHANG J, ZHANG WH, et al. HBsAg loss with Pegylated-interferon alfa-2a in hepatitis B patients with partial response to nucleos(t)ide analog: New Switch study[J]. Chin J Hepatol, 2018, 26(10): 756-764. DOI: 10.3760/cma.j.issn.1007-3418.2018.10.005.

    胡鹏, 尚佳, 张文宏, 等. 核苷(酸)类似物治疗部分应答的乙型肝炎患者通过聚乙二醇干扰素α-2a治疗获得HBsAg消失: New Switch研究[J]. 中华肝脏病杂志, 2018, 26(10): 756-764. DOI: 10.3760/cma.j.issn.1007-3418.2018.10.005.
    [15] LIN B, HA NB, LIU A, et al. Low incidence of hepatitis B e antigen seroconversion in patients treated with oral nucleos(t)ides in routine practice[J]. J Gastroenterol Hepatol, 2013, 28(5): 855-860. DOI: 10.1111/jgh.12108.
    [16] ZOUTENDIJK R, HANSEN BE, van VUUREN AJ, et al. Serum HBsAg decline during long-term potent nucleos(t)ide analogue therapy for chronic hepatitis B and prediction of HBsAg loss[J]. J Infect Dis, 2011, 204(3): 415-418. DOI: 10.1093/infdis/jir282.
    [17] CHEN XY, LIU YL. How patients with hepatitis B get really recovered[J]. J Prac Hepatol, 2016, 19(3): 257-260. DOI: 10.3969/j.issn.1672-5069.2016.03.001.

    陈新月, 刘雅立. 慢性乙型肝炎患者如何获得临床治愈[J]. 实用肝脏病杂志, 2016, 19(3): 257-260. DOI: 10.3969/j.issn.1672-5069.2016.03.001.
  • 加载中
表(4)
计量
  • 文章访问数:  69
  • HTML全文浏览量:  13
  • PDF下载量:  27
  • 被引次数: 0
出版历程
  • 收稿日期:  2021-01-15
  • 修回日期:  2021-02-19
  • 刊出日期:  2021-08-16
  • 分享
  • 用微信扫码二维码

    分享至好友和朋友圈

目录

    /

    返回文章
    返回