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儿童肝炎伴发粒细胞减少的临床特征及其进展为再生障碍性贫血的危险因素分析

曹丽丽 闫建国 董漪 朱世殊 徐志强 王福川 王璞 李爱芹 王丽旻 张敏

曹丽丽, 闫建国, 董漪, 等. 儿童肝炎伴发粒细胞减少的临床特征及其进展为再生障碍性贫血的危险因素分析[J]. 临床肝胆病杂志, 2021, 37(7): 1603-1608. DOI: 10.3969/j.issn.1001-5256.2021.07.025
引用本文: 曹丽丽, 闫建国, 董漪, 等. 儿童肝炎伴发粒细胞减少的临床特征及其进展为再生障碍性贫血的危险因素分析[J]. 临床肝胆病杂志, 2021, 37(7): 1603-1608. DOI: 10.3969/j.issn.1001-5256.2021.07.025
CAO LL, YAN JG, DONG Y, et al. Clinical features of children with hepatitis and granulocytopenia and risk factors for progression to aplastic anemia[J]. J Clin Hepatol, 2021, 37(7): 1603-1608. DOI: 10.3969/j.issn.1001-5256.2021.07.025
Citation: CAO LL, YAN JG, DONG Y, et al. Clinical features of children with hepatitis and granulocytopenia and risk factors for progression to aplastic anemia[J]. J Clin Hepatol, 2021, 37(7): 1603-1608. DOI: 10.3969/j.issn.1001-5256.2021.07.025

儿童肝炎伴发粒细胞减少的临床特征及其进展为再生障碍性贫血的危险因素分析

DOI: 10.3969/j.issn.1001-5256.2021.07.025
基金项目: 

首都临床特色应用研究 Z181100001718030

详细信息
    通讯作者:

    张敏,gcmw2001@163.com

  • 中图分类号: R575

Clinical features of children with hepatitis and granulocytopenia and risk factors for progression to aplastic anemia

Funds: 

Project on the Application of Clinical Characteristics in the Capital Z181100001718030

  • 摘要:   目的  总结儿童肝炎伴发粒细胞减少的发生率和临床特征,分析其进展为再生障碍性贫血(AA)的危险因素。  方法  回顾性选取2014年7月—2020年3月解放军总医院第五医学中心肝病医学部肝病科因肝功异常住院的≤18岁患儿2944例,统计病程中新发血象中性粒细胞减少(<1.5×109/L)患儿的临床特点及病情转归,分析其进展为AA的危险因素。正态分布的计量资料2组间比较采用t检验;非正态分布的计量资料2组间比较采用Wilcoxon秩和检验。计数资料2组间比较采用χ2检验。危险因素采用logistic回归分析。  结果  2944例以肝功能异常入院的儿童中38例为肝炎伴发粒细胞减少,发生率为1.3%。68.4%(26/38)为药物性肝损伤、2.6%(1/38)为自身免疫性肝炎、28.9%(11/38)为不明原因肝损伤。血液异常表现为粒细胞减少症21.1%(8/38),粒细胞减少+三系下降47.4%(18/38),粒细胞缺乏症7.9%(3/38),粒细胞缺乏+三系下降23.7%(9/38)。骨髓细胞学检查,14例(36.8%)诊断为肝炎相关再生障碍性贫血(HAAA),24例(63.2%)为非HAAA。HAAA组与非HAAA组的CD4+(8.5% vs 17%,P=0.008)、CD4+/CD8+(0.17 vs 0.47,P=0.015)比较差异均有统计学意义。进一步多因素logistic回归分析发现CD4+下降为HAAA发生的危险因素(OR=0.009, 95%CI: 0~0.838,P<0.05)。38例患儿均常规保肝、降酶、退黄治疗。14例HAAA患儿中6例免疫抑制剂治疗,7例异基因骨髓移植,血象逐渐恢复,1例因重型AA死亡;24例非HAAA患儿中23例经治疗血象逐渐恢复正常,1例因急性肝衰竭死亡。  结论  儿童肝炎伴发粒细胞减少需警惕AA,尤以药物性或不明原因多见,其中CD4+下降可作为AA的预测因子。

     

  • 表  1  38例肝炎患儿发生血象异常的类型及分布特点

    项目 粒细胞减少症(n=8) 粒细胞缺乏症(n=3) 粒细胞减少+ 三系下降(n=18) 粒细胞缺乏+ 三系下降(n=9) 总计
    病因(例)
      药物 6 1 14 5 26
      不明原因 2 2 3 4 11
      自身免疫性肝炎 0 0 1 0 1
    发生时间(d) 19.0(6.5~55.5) 105.0(27~140) 42.0(28~73) 30.0(27.5~63.5)
    发病时期(例)
      极期 2 0 6 2 10
      恢复期 6 3 12 7 28
    HAAA(例) 0 0 5 9 14
    骨穿结果(例)
      增生减低 1 1 7 8 17
      增生活跃 6 2 9 1 18
      未做 1 0 2 0 3
    下载: 导出CSV

    表  2  38例肝炎患儿粒细胞减少时生化、血象及免疫学指标与肝炎发病时的比较

    指标 肝炎发病时 发生粒细胞减少时 统计值 P
    ALT(U/L) 1 141.00(644.58~1 482.13) 206.00(65.25~592.75) Z=4.805 <0.001
    AST(U/L) 1 005.00(714.63~1 489.28) 185.00(72.00~735.50) Z=4.473 <0.001
    TBil(μmol/L) 199.35(115.85~270.48) 66.75(26.75~205.33) Z=3.719 <0.001
    DBil(μmol/L) 148.85(76.75~211.88) 52.50(18.30~170.40) Z=2.587 0.010
    PTA(%) 65.17±17.02 93.3±26.98 t=6.635 <0.001
    WBC(×109/L) 5.10±2.85 3.03±1.61 t=5.802 <0.001
    NEUT(×109/L) 3.19±2.52 1.69±1.37 t=5.047 <0.001
    RBC(×1012/L) 4.46±0.57 3.88±0.72 t=5.377 <0.001
    Hb(g/L) 126.66±16.15 114.24±18.54 t=5.591 <0.001
    PLT(×109/L) 204.00±113.23 128.37±113.16 t=4.490 <0.001
    T淋巴细胞(%) 69.89±14.33 68.29±17.26 t=0.951 0.348
    CD4+(%) 18.50±14.08 19.39±15.22 t=1.384 0.175
    CD8+(%) 44.16±18.04 43.05±19.04 t=0.773 0.445
    CD4+/CD8+ 0.28(0.15~0.73) 0.35(0.15~0.80) Z=0.918 0.359
    下载: 导出CSV

    表  3  38例肝炎伴发粒细胞减少患儿的治疗及预后

    项目 粒细胞减少症 粒细胞缺乏症 粒细胞减少+三系下降 粒细胞缺乏+三系下降 总计
    常规治疗(例) 5 1 12 3 21
    激素和/或丙种球蛋白治疗(例) 3 2 6 6 17
    HAAA治疗(例)
      ATG序贯CsA 0 0 1 0 1
      CsA 0 0 3 2 5
      allo-HSCT 0 0 2 5 7
    转归(例)
      恢复 7 3 18 8 36
      死亡 1 0 0 1 2
    下载: 导出CSV

    表  4  儿童肝炎伴发粒细胞减少发生AA的单因素分析

    因素 HAAA组(n=14) 非HAAA组(n=24) 统计值 P
    男性[例(%)] 11(78.6) 13(54.2) χ2=2.263 1.132
    年龄(岁) 9.8(5.7~11.2) 10.8(9.5~13.5) Z=1.181 0.238
    BMI(kg/m2) 18.80±2.01 16.96±3.11 t=1.965 0.057
    病因(药物)[例(%)] 7(50.0) 19(79.2) χ2=3.481 0.062
    皮疹[例(%)] 2(14.3) 6(25.0) χ2=0.684 0.365
    感染[例(%)] 8(57.1) 12(50.0) χ2=0.181 0.671
    激素[例(%)] 7(50.0) 10(41.7) χ2=0.248 0.618
    ALT(U/L) 1 218.5(730.0~1 668.0) 796.0(422.0~1 471.0) Z=1.210 0.226
    AST(U/L) 1 082.9(337.0~1 328.0) 971.0(669.0~1 590.0) Z=0.393 0.694
    TBil(μmol/L) 263.8(156.0~308.0) 241.6(163.6~354.3) Z=0.030 0.976
    WBC(×109/L) 5.22(2.50~6.70) 4.67(2.88~6.15) Z=0.303 0.762
    NEUT(×109/L) 3.17(1.51~4.51) 2.34(1.48~3.82) Z=0.832 0.405
    T淋巴细胞百分比(%) 67.5(53.5~80.5) 73.0(63.0~81.0) Z=1.014 0.310
    CD4+(%) 8.5(6.5~14.5) 17.0(10.0~43.0) Z=2.638 0.008
    CD8+(%) 47.5(35.5~60.0) 33.0(25.0~60.0) Z=1.499 0.134
    CD4+/CD8+ 0.17(0.15~0.35) 0.47(0.18~1.44) Z=2.422 0.015
    下载: 导出CSV
  • [1] QI PJ, ZHENG J, MA J, et al. Clinical features and treatment outcome of hepatitis associated aplastic anemia in 43 children[J]. Chin J Appl Clin Pediatr, 2017, 32(3): 216-219. DOI: 10.3760/cma.j.issn.2095-428X.2017.03.013.

    漆佩静, 郑杰, 马洁, 等. 儿童肝炎相关再生障碍性贫血43例临床特征及治疗转归分析[J]. 中华实用儿科临床杂志, 2017, 32(3): 216-219. DOI: 10.3760/cma.j.issn.2095-428X.2017.03.013.
    [2] Chinese Society of Infectious Diseases and Parasitology, Chinese Society of Hepatology, Chinese Medical Association. Prevention and treatment of viral hepatitis[J]. Chin J Infect Dis, 2001, 19(1): 56-62. DOI: 10.3760/j.issn:1000-6680.2001.01.027.

    中华医学会传染病与寄生虫病学分会、肝病学分会. 病毒性肝炎防治方案[J]. 中华传染病杂志, 2001, 19(1): 56-62. DOI: 10.3760/j.issn:1000-6680.2001.01.027.
    [3] Drug-induced Liver Disease Study Group, Chinese Society of Hepatology, Chinese Medical Association. Guidelines for the management of drug-induced liver injury[J]. J Clin Hepatol, 2015, 31(11): 1752-1768. DOI: 10.3760/cma.j.issn.1007-3418.2015.11.004.

    中华医学会肝病学分会药物性肝病学组. 药物性肝损伤诊治指南(2015年版)[J]. 临床肝胆病杂志, 2015, 31(11): 1752-1768. DOI: 10.3760/cma.j.issn.1007-3418.2015.11.004.
    [4] Chinese Society of Hepatology, Chinese Medical Association; Chinese Society of Gastroenterology, Chinese Medical Association; Chinese Society of Infectious Diseases, Chinese Medical Association. Consensus on the diagnosis and management of autoimmune hepatitis (2015)[J]. J Clin Hepatol, 2016, 32(1): 9-22. DOI: 10.3969/j.issn.100l-5256.2016.01.002.

    中华医学会肝病学分会, 中华医学会消化病学分会, 中华医学会感染病学分会. 自身免疫性肝炎诊断和治疗共识(2015)[J]. 临床肝胆病杂志, 2016, 32(1): 9-22. DOI: 10.3969/j.issn.100l-5256.2016.01.002.
    [5] BARONE A, LUCARELLI A, ONOFRILLO D, et al. Diagnosis and management of acquired aplastic anemia in childhood. Guidelines from the Marrow Failure Study Group of the Pediatric Haemato-Oncology Italian Association (AIEOP)[J]. Blood Cells Mol Dis, 2015, 55(1): 40-47. DOI: 10.1016/j.bcmd.2015.03.007.
    [6] Study Group of Hematology, Chinese Pediatric Society, Chinese Medical Association; Editorial Board of Chinese Journal of Pediatrics. Recommendation for the diagnosis and treatment of acquired aplastic anemia in children[J]. Chin J Pediatr, 2014, 52(2): 103-106. DOI: 10.3760/cma.j.issn.0578-1310.2014.02.006.

    中华医学会儿科学分会血液学组, 《中华儿科杂志》编辑委员会. 儿童获得性再生障碍性贫血诊疗建议[J]. 中华儿科杂志, 2014, 52(2): 103-106. DOI: 10.3760/cma.j.issn.0578-1310.2014.02.006.
    [7] RAUFF B, IDREES M, SHAH SA, et al. Hepatitis associated aplastic anemia: A review[J]. Virol J, 2011, 8: 87. DOI: 10.1186/1743-422X-8-87.
    [8] LOCASCIULLI A, BACIGALUPO A, BRUNO B, et al. Hepatitis-associated aplastic anaemia: Epidemiology and treatment results obtained in Europe. A report of The EBMT aplastic anaemia working party[J]. Br J Haematol, 2010, 149(6): 890-895. DOI: 10.1111/j.1365-2141.2010.08194.x.
    [9] WANG HQ, TU MF, FU R, et al. The clinical and immune characteristics of patients with hepatitis-associated aplastic anemia in China[J]. PLoS One, 2014, 9(5): e98142. DOI: 10.1371/journal. Pope.0098142.
    [10] QIAO XH, XIE XT, SHI W, et al. Clinic features of hepatitis associated aplastic anemia for children by evidence-based medical analysis[J]. Chin J Appl Clin Pediatr, 2013, 28(15): 1155-1158. DOI: 10.3760/cma.j.issn.2095-428X. 2013.15.011.

    乔晓红, 谢晓恬, 石苇, 等. 儿童肝炎相关再生障碍性贫血循证医学分析[J]. 中华实用儿科临床杂志, 2013, 28(15): 1155-1158. DOI: 10.3760/cma.j.issn.2095-428X. 2013.15.011.
    [11] MOLLESTON JP, FONTANA RJ, LOPEZ MJ, et al. Characteristics of idiosyncratic drug-induced liver injury in children: Results from the DILIN prospective study[J]. J Pediatr Gastroenterol Nutr, 2011, 53(2): 182-189. DOI: 10.1097/MPG.0b013e31821d6cfd.
    [12] GAFAR F, ARIFIN H, JURNALIS YD, et al. Antituberculosis drug-induced liver injury in children: Incidence and risk factors during the two-month intensive phase of therapy[J]. Pediatr Infect Dis, 2019, 38: 50-53. DOI: 10.1097/INF.0000000000002192.
    [13] DANAN G, BENICHOU E. Causality assessment of adverse reactions to drugs-I. A novel method based on the conclusions of international consensus meetings: Application to drug-induced liver injuries[J]. Clin Epidemiol, 1993, 46: 1323-1330. DOI: 10.1016/0895-4356(93)90101-6.
    [14] CHEN Y, LIN N, SUN M. Clinical research of childhood hepatitis-associated aplastic anemia[J]. Chin Pediatr Emerg Med, 2015, 22(9): 603-606. DOI: 10.3760/cma.j.issn.1673-4912.2015.09.003.

    陈莹, 林楠, 孙梅. 儿童肝炎相关性再生障碍性贫血临床特征研究[J]. 中国小儿急救医学, 2015, 22(9): 603-606. DOI: 10.3760/cma.j.issn.1673-4912.2015.09.003.
    [15] MU J, CHEN F, HE Q. Hepatitis-associated aplastic anaemia in children: A case report[J]. J Clin Hepatol, 2019, 35(8): 1797-1799. DOI: 10.3969/j.issn.1001-5256.2019.08.029.

    穆静, 陈芳, 何强. 儿童肝炎相关再生障碍性贫血1例报告[J]. 临床肝胆病杂志, 2019, 35(8): 1797 -1799. DOI: 10.3969/j.issn.1001-5256.2019.08.029.
    [16] RAUFF B, IDREES M, SHAH SA, et al. Hepatitis associated aplastic anemia: A review[J]. Virol J, 2011, 8: 87. DOI: 10.1186/1743-422X-8-87.
    [17] WANG H, TU M, FU R, et al. The clinical and immune characteristics of patients with hepatitis-associated aplastic anemia in China[J]. PLoS One, 2014, 9(5): e98142. DOI: 10.1371/journal.pone.0098142.
    [18] BABUSHOK DV, GRIGNON AL, LI Y, et al. Disrupted lymphocyte homeostasis in hepatitis-associated acquired aplastic anemia is associated with short telomeres[J]. Am J Hematol, 2016, 91(2): 243-247. DOI: 10.1002/ajh.24256.
    [19] ALSAKKAL M, AL-KHATEEB M, ALHALABY M, et al. Hepatitis-associated aplastic anemia: A report of 3 cases associated with HAV[J]. J Pediatr Hematol Oncol, 2019, 41(3): e164, e166. DOI: 10.1097/MPH.0000000000001199.
    [20] ZHANG XM, LUO RM. Progress in diagnosis and treatment of hepatitis associated aplastic in children[J]. Infect Dis Info, 2019, 32(2): 171-174. DOI: 10.3969/j.issn.1007-8134.2019.02.019.

    张晓妹, 罗荣牡. 儿童肝炎相关再生障碍性贫血的诊治进展[J]. 传染病信息, 2019, 32(2): 171-174. DOI: 10.3969/j.issn.1007-8134.2019.02.019.
    [21] IKEDA T, MORIMOTO A, NAKAMURA S, et al. A marked decrease in CD4-positive lymphocytes at the onset of hepatitis in a patient with hepatitis-associated aplastic anemia[J]. J Pediatr Hematol Oncol, 2012, 34(5): 375-377. DOI: 10.1097/MPH.0b013e31822bf699.
    [22] McKENZIE RB, BERQUIST WE, NADEAU KC, et al. Novel protocol including liver biopsy to identify and treat CD8+ T-cell predominant acute hepatitis and liver failure[J]. Pediatr Transplant, 2014, 18(5): 503-509. DOI: 10.1111/petr.12296.
    [23] GONÇALVES V, CALADO R, PALARÉ MJ, et al. Hepatitis-associated aplastic anaemia: A poor prognosis[J]. BMJ Case Rep, 2013, 2013: bcr2012007968. DOI: 10.1136/bcr-2012-007968.
    [24] TU MF, SHAO ZH, LIU H, et al. The clinical features of hepatitis associated aplastic anemia[J]. Chin J Hemotal, 2005, 26(4): 239-242. DOI: 10.3760/j:issn:0253-2727.2005.04.012.

    涂梅峰, 邵宗鸿, 刘鸿, 等. 肝炎相关再生障碍性贫血的临床特征[J]. 中华血液学杂志, 2005, 26(4): 239-242. DOI: 10.3760/j:issn:0253-2727.2005.04.012.
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  • 收稿日期:  2020-11-18
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