中文English
ISSN 1001-5256 (Print)
ISSN 2097-3497 (Online)
CN 22-1108/R
Volume 37 Issue 7
Jul.  2021
Turn off MathJax
Article Contents

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

DOI: 10.3969/j.issn.1001-5256.2021.07.025
Research funding:

Project on the Application of Clinical Characteristics in the Capital (Z181100001718030)

  • Received Date: 2020-11-18
  • Accepted Date: 2021-03-08
  • Published Date: 2021-07-20
  •   Objective  To investigate the incidence rate and clinical features of children with hepatitis and granulocytopenia and the risk factors for progression to aplastic anemia (AA).  Methods  A retrospective analysis was performed for 2944 children, aged ≤18 years, who were hospitalized due to abnormal liver function in Pediatric Liver Diseases Treatment and Research Center, The Fifth Medical Center of Chinese PLA General Hospital, from July 2014 to March 2020. Clinical features and prognosis were analyzed for children with new-onset neutropenia (< 1.5×109/L) during the course of the disease, and the risk factors for progression to AA were analyzed. The t-test was used for comparison of normally distributed continuous data between groups, and the Wilcoxon rank-sum test was used for comparison of non-normally distributed continuous data between groups; the chi-square test was used for comparison of categorical data between groups. A logistic regression analysis was used to investigate risk factors.  Results  Among the 2944 children admitted due to abnormal liver function, 38 had hepatitis with granulocytopenia, with an incidence rate of 1.3%. Among these 38 children, 68.4% (26/38) had drug-induced liver injury, 2.6% (1/38) had autoimmune hepatitis, and 28.9% (11/38) had unexplained liver injury; as for blood abnormalities, 21.1% (8/38) had granulocytopenia, 47.4% (18/38) had granulocytopenia and reductions in three lines of blood cells, 7.9% (3/38) had agranulocytosis, and 23.7% (9/38) had agranulocytosis and reductions in three lines of blood cells. Bone marrow cytology showed that among the 38 children, 14 (36.8%) were diagnosed with hepatitis-associated AA (HAAA) and 24 (63.2%) were diagnosed with non-HAAA. In order to analyze the risk factors for HAAA, there were significant differences in CD4+ (8.5% vs 17%, P=0.008) and CD4+/CD8+ ratio (0.17 vs 0.47, P=0.015) between the HAAA group and the non-HAAA group. Further multivariate logistic regression analysis showed that the reduction in CD4+ was a risk factor for HAAA (β=-4.757, P < 0.05). All 38 children were given routine liver-protecting, transaminase-lowering, and jaundice clearance treatment. Among the 14 children with HAAA, 6 had gradual recovery of hemogram after immunosuppressant therapy, 7 had gradual recovery of hemogram after allogeneic hematopoietic stem cell transplantation, and 1 died due to severe AA; among the 24 children with non-HAAA, 23 had hemogram gradually returning to normal after treatment, and 1 died of acute liver failure.  Conclusion  AA should be taken seriously for children with hepatitis and granulocytopenia, especially for those with drug-induced or unexplained liver injury, and the reduction in CD4+ may be used as a predictive factor for AA.

     

  • loading
  • [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.
  • 加载中

Catalog

    通讯作者: 陈斌, bchen63@163.com
    • 1. 

      沈阳化工大学材料科学与工程学院 沈阳 110142

    1. 本站搜索
    2. 百度学术搜索
    3. 万方数据库搜索
    4. CNKI搜索

    Tables(4)

    Article Metrics

    Article views (770) PDF downloads(46) Cited by()
    Proportional views
    Related

    /

    DownLoad:  Full-Size Img  PowerPoint
    Return
    Return