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儿童慢性乙型肝炎肝组织HBsAg、HBcAg的表达与抗病毒疗效的关系

王丽旻 刘树红 朱世殊 董漪 徐志强 王福川 闫建国 王璞 李爱芹 曹丽丽 赵攀 张敏

王丽旻, 刘树红, 朱世殊, 等. 儿童慢性乙型肝炎肝组织HBsAg、HBcAg的表达与抗病毒疗效的关系[J]. 临床肝胆病杂志, 2021, 37(1): 46-50. DOI: 10.3969/j.issn.1001-5256.2021.01.010
引用本文: 王丽旻, 刘树红, 朱世殊, 等. 儿童慢性乙型肝炎肝组织HBsAg、HBcAg的表达与抗病毒疗效的关系[J]. 临床肝胆病杂志, 2021, 37(1): 46-50. DOI: 10.3969/j.issn.1001-5256.2021.01.010
WANG LM, LIU SH, ZHU SH, et al. Association of the expression of HBsAg and HBcAg in liver tissue with antivi-ral response in children with chronic hepatitis B[J]. J Clin Hepatol, 2021, 37(1): 46-50. DOI: 10.3969/j.issn.1001-5256.2021.01.010
Citation: WANG LM, LIU SH, ZHU SH, et al. Association of the expression of HBsAg and HBcAg in liver tissue with antivi-ral response in children with chronic hepatitis B[J]. J Clin Hepatol, 2021, 37(1): 46-50. DOI: 10.3969/j.issn.1001-5256.2021.01.010

儿童慢性乙型肝炎肝组织HBsAg、HBcAg的表达与抗病毒疗效的关系

DOI: 10.3969/j.issn.1001-5256.2021.01.010
基金项目: 

首都特色课题 Z161100000516176

北京自然科学基金 7202193

国家十三五重大专项课题 2018ZX10301-404

详细信息
    作者简介:

    王丽旻(1976—),女,副主任医师,博士,主要从事儿童肝病研究

    通讯作者:

    张敏,gcmw2001@163.com

  • 利益冲突声明:本研究不存在研究者、伦理委员会成员、受试者监护人以及与公开研究成果有关的利益冲突,特此声明。
  • 作者贡献声明:王丽旻负责课题设计,资料分析,撰写论文;刘树红、朱世殊、董漪、徐志强、王福川、闫建国、王璞、李爱芹、曹丽参与收集数据,修改论文;赵攀、张敏负责拟定写作思路,指导撰写文章,并最后定稿。
  • 中图分类号: R512.62

Association of the expression of HBsAg and HBcAg in liver tissue with antiviral response in children with chronic hepatitis B

  • 摘要:   目的  探索性研究慢性乙型肝炎(CHB)儿童肝组织HBsAg和HBcAg不同表达与抗病毒疗效的关系。  方法  收集2014年1月—2017年12月在解放军总医院第五医学中心青少年肝病科住院并明确诊断为CHB的276例6月~16岁儿童患者的病例资料,比较肝组织HBsAg和HBcAg免疫组化染色阳性和阴性组(HBsAg阳性组249例, HBsAg阴性组27例; HBcAg阳性组163例,HBcAg阴性组113例)患者的临床特点,以及肝组织HBsAg和HBcAg不同表达模式下抗病毒疗效的差异。计量资料组间比较采用Mann-Whitney U检验;计数资料组间比较采用χ2检验或Fisher精确检验。以肝组织HBsAg和HBcAg染色阳性和阴性为应变量,以可能影响其表达强度有意义的相关因素为自变量,进行logistic回归分析。  结果  276例患者年龄0.5~16岁,男性占60.51%(167例)。HBeAg阴性14例(5.07%)。肝脏炎症程度分级(G):2级52.54%,2~3级6.88%,3级7.61%。肝纤维化分期(S):3期7.25%, 3~4期1.45%,4期3.62%。肝组织HBsAg阳性组儿童年龄及血清HBsAg定量高于阴性组(Z值分别为1.854、2.447, P值均<0.05)。肝组织HBcAg阳性组HBeAg阳性率高于阴性组(χ2=2.650),ALT(Z=2.473)、AST(Z=1.813)、肝组织纤维化分期S≥3期的比例(χ2=2.086)均低于阴性组(P值均<0.05)。logistic回归分析显示,影响肝组织HBsAg染色阳性的因素为血清HBsAg定量(P<0.05),影响肝组织HBcAg染色阳性的因素为HBeAg阴性或阳性(P<0.05)。276患者中186例完成IFNα或单用拉米夫定抗病毒治疗停药后6个月的随访,155例(83.33%)获得HBeAg血清学转换,其中76例(40.86%)HBsAg阴转。肝组织的HBsAg阳性表达强度越高,血清HBsAg阴转率越低。肝组织的HBcAg阳性表达强度越高,HBeAg血清学转换率越低。肝组织HBsAg及HBcAg均阴性表达模式的儿童HBsAg阴转率最高(100%),HBsAg阳性及HBcAg阴性的儿童HBsAg阴转率(32.31%)最低。  结论  肝组织HBsAg及HBcAg阴性的CHB儿童抗病毒治疗HBsAg阴转率最高
  • 表  1  儿童肝组织HBsAg与HBcAg不同分组各临床基线指标的比较

    指标 HBsAg HBcAg
    阳性组(n=249) 阴性组(n=27) 统计值 P 阳性组(n=163) 阴性组(n=113) 统计值 P
    年龄(岁) 5.00(2.67~11.00) 4.25(2.08~7.00) Z=1.854 0.041 5.00(2.50~10.00) 4.83(2.58~7.67) Z=0.892 0.113
    男性[例(%)] 151(60.64) 16(59.26) χ2=0.140 0.890 97(59.51) 70(61.95) χ2=0.407 0.683
    母亲HBsAg阳性[例(%)] 191(76.71) 22(81.48) χ2=0.222 0.824 123(75.46) 90(79.65) χ2=0.815 0.417
    ALT (U/L) 99.0(56.0~192.0) 98.0(64.5~153.0) Z=0.478 0.612 95.0(61.0~175.5) 113.0(50.0~214.0) Z=2.473 0.021
    AST (U/L) 82.0(57.0~170.0) 75.0(58.0~110.5) Z=0.876 0.239 78.0(48.0~133.0) 91.0(53.0~177.0) Z=1.813 0.043
    HBsAg定量(IU/ml) 11 155.5(4299.0~30 119.3) 3884.2(892.7~18 289.0) Z=2.447 0.023 18 195.0(5461.0~32 602.8) 7882.5(3002.0~16 083.3) Z=0.824 0.417
    HBeAg阳性[例(%)] 223(89.56) 25(92.59) 1.0001) 153(93.87) 95(84.07) χ2=2.650 0.008
    HBV DNA(lg IU/ml) 7.45 (6.83~8.65) 6.28 (5.14~8.05) Z=0.891 0.223 7.57(6.35~8.42) 7.05(6.11~8.11) Z=0.921 0.368
    肝组织炎症分级[例(%)] χ2=0.904 0.366 χ2=0.848 0.396
      G<2 80(32.13) 11(40.74) 57(34.97) 34(30.09)
      G≥2 169(67.87) 16(59.26) 106(65.03) 79(69.91)
    肝组织纤维化分期[例(%)] 0.5411) χ2=2.086 0.037
      S<3 217(87.15) 25(92.59) 148(90.80) 93(82.30)
      S≥3 32(12.85) 2(7.41) 15(9.20) 20(17.70)
    注:1)为Fisher精确检验。
    下载: 导出CSV

    表  2  186例完成治疗的儿童治疗前肝组织HBsAg、HBcAg表达不同疗效的差异

    项目 例数
    (n=186)
    HBeAg转换
    (n=155)
    HBsAg阴转
    (n=76)
    HBsAg[例(%)]
      - 21(11.29) 20(95.24) 19(90.48)
      + 125(67.20) 100(80.00) 50(40.00)
      ++ 34(18.28) 31(91.18) 6(17.65)
      +++ 6(8.11) 4(66.67) 1(16.67)
    HBcAg[例(%)]
      - 74(39.78) 64(86.49) 30(40.54)
      + 101(54.30) 85(84.16) 41(40.59)
      ++ 9(4.84) 5(55.56) 4(44.44)
      +++ 2(1.08) 1(50.00) 1(50.00)
    下载: 导出CSV

    表  3  肝组织HBsAg、HBcAg 4种表达方式抗病毒疗效的差异

    组别 例数
    (n=186)
    HBeAg转换
    (n=155)
    HBsAg阴转
    (n=76)
    HBsAg(-)HBcAg(-)[例(%)] 9(4.84) 9(100.00) 9(100.00)
    HBsAg(-)HBcAg(+)[例(%)] 12(6.45) 11(91.67) 10(83.33)
    HBsAg(+)HBcAg(-)[例(%)] 65(34.95) 55(84.62) 21(32.31)
    HBsAg(+)HBcAg(+)[例(%)] 100(53.76) 80(80.00) 36(36.00)
    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. (in Chinese) 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] WU JZ, WANG LC. Comparison of clinical manifestation and hepatic pathology in patients with chronic hepatitis B with negative and positive expression of HBcAg and HBsAg in liver tissue[J]. Sichuan Med J, 2017, 38(1): 32-35. (in Chinese) https://www.cnki.com.cn/Article/CJFDTOTAL-SCYX201701013.htm

    吴家箴, 王丽春. 肝组织内HBsAg、HBcAg表达阴性与阳性的慢性乙型肝炎患者临床及肝脏病理的比较[J]. 四川医学, 2017, 38(1): 32-35. https://www.cnki.com.cn/Article/CJFDTOTAL-SCYX201701013.htm
    [3] YING S, HU AR, JIANG SW, et al. Expression intensity and clinical significance of intrahepatic hepatitis B surface antigen and hepatitis B core antigen in 994 patients with chronic hepatitis B virus infection[J]. Chin J Clin Infect Dis, 2017, 10(4): 250-256. (in Chinese) DOI: 10.3760/cma.j.issn.1674-2397.2017.04.002

    应盛, 胡爱荣, 蒋素文, 等. 慢性乙型肝炎病毒感染者994例肝组织HBsAg和HBcAg表达强度的临床意义[J]. 中华临床感染病杂志, 2017, 10(4): 250-256. DOI: 10.3760/cma.j.issn.1674-2397.2017.04.002
    [4] WU JZ, HUANG RG, YANG XX, et al. Association of serum HBeAg, expression intensity of HBsAg and HBcAg in hepatic tissue with clinical characteristics in 317 chronic hepatitis B patients[J]. Chongqing Med, 2017, 46(4): 468-471. (in Chinese) DOI: 10.3969/j.issn.1671-8348.2017.04.012

    吴家箴, 黄仁刚, 杨兴祥, 等. 317例慢性乙型肝炎患者血清HBeAg、肝组织内HBsAg和HBcAg表达强度与临床的关系[J]. 重庆医学, 2017, 46(4): 468-471. DOI: 10.3969/j.issn.1671-8348.2017.04.012
    [5] TAN L, WU T, LYU Y, et al. HBsAg levels normalized to the same hepatic parenchyma cell volume is correlated with pathological progression but not HBeAg status[J]. J Sun Yat-Sen Univ(Medical Sciences) 2019, 40(5): 747-753. (in Chinese) https://www.cnki.com.cn/Article/CJFDTOTAL-ZSYK201905014.htm

    谭雷, 吴涛, 吕艳, 等. 经相同肝实质细胞体积分摊的血清HBsAg水平与肝组织病理进展相关而与HBeAg状态无关[J]. 中山大学学报(医学版), 2019, 40(5): 747-753. https://www.cnki.com.cn/Article/CJFDTOTAL-ZSYK201905014.htm
    [6] 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. (in Chinese) 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
    [7] ZHU SS, DONG Y, WANG LM, et al. Early initiation of antiviral therapy contributes to a rapid and significant loss of serum HBsAg in infantile-onset hepatitis B[J]. J Hepatol, 2019, 71: 871-875. DOI: 10.1016/j.jhep.2019.06.009
    [8] ZHU SS, ZHANG HF, DONG Y, et al. Antiviral therapy in hepatitis B virus-infected children with immune-tolerant characteristics: A pilot open-label randomized study[J]. J Hepatol, 2018, 68(8): 1123-1128.
    [9] CHU CM, YEH CT, SHEEN IS, et al. Subcellular localization of hepatitis B core antigen in relation to hepatocyte regeneration in chronic hepatitis B[J]. Gastroenterology, 1995, 109(6): 1926-1932. DOI: 10.1016/0016-5085(95)90760-2
    [10] ZHU SS, DONG Y, ZHANG HF, et al. The etiology and multivariate statistical analysis of outcome of 185 children with liver failure[J]. Chin J Pract Pediatr, 2014, 29(3): 205-208. (in Chinese) https://www.cnki.com.cn/Article/CJFDTOTAL-ZSEK201403014.htm

    朱世殊, 董漪, 张鸿飞, 等. 儿童肝衰竭185例病因及转归多因素分析[J]. 中国实用儿科杂志, 2014, 29(3): 205-208. https://www.cnki.com.cn/Article/CJFDTOTAL-ZSEK201403014.htm
    [11] ZHANG HF, DONG Y, WANG LM, et al. A retrospective study on pathological and clinical characteristics of 3932 children with liver diseases[J]. Chin J Pediatr, 2014, 52(8): 570-574. (in Chinese) DOI: 10.3760/cma.j.issn.0578-1310.2014.08.004

    张鸿飞, 董漪, 王丽旻, 等. 儿童肝穿刺组织病理与临床诊断3932例回顾性研究[J]. 中华儿科杂志, 2014, 52(8): 570-574. DOI: 10.3760/cma.j.issn.0578-1310.2014.08.004
    [12] ZHU SS, DONG Y, XU ZQ, et al. A retrospective study on HBsAg clearance rate after anfiviral therapy in children with HBeAg-positive chronic hepatitis B aged 1-7 years[J]. Chin J Hepatol, 2016, 24(10): 738-743. (in Chinese) DOI: 10.3760/cma.j.issn.1007-3418.2016.10.005

    朱世殊, 董漪, 徐志强, 等. 1~7岁慢性乙型肝炎HBeAg阳性儿童经抗病毒治疗HBsAg清除率的回顾性研究[J]. 中华肝脏病杂志, 2016, 24(10): 738-743. DOI: 10.3760/cma.j.issn.1007-3418.2016.10.005
    [13] TANG QY, HE Q, LE XH, et al. Relationships between the distribution of HBcAg in hepatocytes and the markers of HBV replication in serum in patients with chronic hepatitis B[J/CD]. Chin J Exp Clin Infect Dis (Electronic Edition), 2011, 5(1): 42-45. (in Chinese)

    唐奇远, 何清, 乐晓华, 等. 慢性乙型肝炎患者肝细胞内HBcAg分布与血清病毒学指标的相关性研究[J/CD]. 中华实验和临床感染病杂志(电子版), 2011, 5(1): 42-45.
    [14] GAO M, LU CZ, WANG Y, et al. Relationship between expression of HBcAg in liver tissue and characteristics of the hepatic pathological features in patients with chronic hepatitis B virus infection[J]. J Clin Hepatol, 2012, 28(3): 201-204. (in Chinese) http://lcgdbzz.xml-journal.net/article/id/LCGD201203013

    高敏, 卢诚震, 王怡, 等. 慢性乙型肝炎病毒感染者肝组织HBcAg表达与临床及病理特征的关系[J]. 临床肝胆病杂志, 2012, 28(3): 201-204. http://lcgdbzz.xml-journal.net/article/id/LCGD201203013
    [15] LIU Y, LI H, YAN X, et al. Long-term efficacy and safety of peginterferon in the treatment of children with HBeAg-positive chronic hepatitis B[J]. J Viral Hepat, 2019, 26(Suppl 1): 69-76. DOI: 10.1111/jvh.13154
    [16] CORNBERG M, WONG VW, LOCARNIMI S, et al. The role of quantitative hepatitis B surface antigen revisited[J]. J Hepatol, 2017, 66(2): 398-411. DOI: 10.1016/j.jhep.2016.08.009
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  • 收稿日期:  2020-07-07
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