Clinical Research

Clinical features of hepatitisassociatedaplastic anemia in children

  • Bingjie QUAN ,
  • Yijing LIU ,
  • Xiaoqin LI ,
  • Fang ZHOU
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  • Department of Digestion,Children's Hospital Affiliated to Zhengzhou University,He′nan Children's Hospital,Zhengzhou Children's Hospital,Zhengzhou 450053,He'nan,China

Received date: 2024-10-08

  Online published: 2025-01-14

Abstract

Objective To investigate the clinical characteristics of hepatitis?associated aplastic anemia (HAAA) in pediatric patients. Methods A retrospective study was conducted on 212 children with aplastic anemia (AA) who were hospitalized at Henan Children's Hospital from September 2014 to February 2023. The patients were categorized into two groups based on etiology: the HAAA group and the non?HAAA group. The study group consisted of 23 patients in the HAAA group, while a control group of 115 children without HAAA was matched in a 1∶5 ratio based on age, sex, and severity of aplastic anemia. The clinical characteristics, treatment regimens, and outcomes of the 23 patients with HAAA were analyzed and compared with those of the control group comprising 115 patients. Results Among the 23 children with HAAA, there were 11 males and 12 females, with a median age of 6 years and 3 months (ranging from 1 year and 4 months to 12 years old). The onset of aplastic anemia in all HAAA children occurred after the initial presentation of acute hepatitis. Following gradual improvement in liver function, peripheral blood images showed a progressive decline by two or three lines, including platelets. Among these cases, very severe aplastic anemia was observed in 14 patients (60.9%), severe aplastic anemia in 7 patients (30.4%), and non?severe aplastic anemia in 2 patients (8.7%). The median interval between hepatitis onset and diagnosis of aplastic anemia was found to be 56 days (range:10 ~ 157 days). All 23 pediatric patients with HAAA presented with acute icteric hepatitis, accounting for 100% of the cohort. One patient (4.3%) was genetically diagnosed with X?linked lymphoproliferative disease type 2, while liver biopsy revealed drug?induced hepatitis/chemical liver injury in five patients (21.7%). Compared to the control group, HAAA patients exhibited significantly lower levels of CD4+ cells [(1.2 ± 0.3) vs. (1.5 ± 0.1)] and CD4+/CD8+ ratios [(-0.2 ± 0.4) vs. (0.1 ± 0.2)] (P < 0.05). Three patients received immunosuppressive therapy (IST), 18 underwent hematopoietic stem cell transplantation (HSCT), and two non?severe cases were treated with methylprednisolone sodium succinate and compound Zapoan pill; all patients survived. Conclusions Children with HAAA present a critical condition and exhibit a poor prognosis, predominantly manifesting as severe or extremely severe aplastic anemia during the recovery phase of hepatitis. Reduction in CD4+ cell count and inversion of CD4+/CD8+ ratio may serve as early warning indicators for HAAA. Effective improvement in prognosis can be achieved through immunosuppressive therapy and hematopoietic stem cell transplantation.

Cite this article

Bingjie QUAN , Yijing LIU , Xiaoqin LI , Fang ZHOU . Clinical features of hepatitisassociatedaplastic anemia in children[J]. The Journal of Practical Medicine, 2025 , 41(1) : 84 -89 . DOI: 10.3969/j.issn.1006-5725.2025.01.014

References

1 KEMME S, STAHL M, BRIGHAM D, et al. Outcomes of Severe Seronegative Hepatitis-associated Aplastic Anemia: A Pediatric Case Series[J]. J Pediatr Gastroenterol Nutr, 2021,72(2):194-201. doi:10.1097/mpg.0000000000002940
2 李晓雷,赵瑞芹,赵雅男,等. 儿童肝炎相关性再生障碍性贫血8例临床特征[J]. 中国小儿血液与肿瘤杂志,2022,27(3):169-172.
3 SANTARELLI I M, MANZELLA P O, GASCO GONZáLEZ F, et al. Hepatitis associated aplastic anemia duringSARS-CoV-2 pandemic[J]. Rev Fac Cien Med Univ Nac Cordoba, 2022,79(2):201-204. doi:10.31053/1853.0605.v79.n2.35138
4 GHANEI-SHAHMIRZADI A, REIHANI H, ABBASI-KASH-KOOLI A,et al. Aplastic anemia: A new complication in the recent mysterious hepatitis outbreak among children worldwide: two case reports[J]. J Med Case Rep,2022,16(1):422. doi:10.1186/s13256-022-03542-0
5 国家卫生健康委办公厅. 儿童再生障碍性贫血诊疗规范(2019年版)[J]. 全科医学临床与教育,2019,17(11):965-969.
6 ALSHAIBANI A, DUFOUR C, RISITANO A, et al. Hepatitis-Associated Aplastic Anemia[J]. Hematol Oncol Stem Cell Ther, 2022,15(2):8-12. doi:10.1016/j.hemonc.2020.10.001
7 王化泉,邵宗鸿. 再生障碍性贫血的排除诊断[J]. 中华医学杂志,2022,102(12):830-832.
8 CAMITTA B M, STORB R, THOMAS E D. Aplastic anemia (first of two parts): Pathogenesis,diagnosis,treatment, and prognosis[J]. N Engl J Med, 1982,306(11):645-652. doi:10.1056/nejm198203183061105
9 LORENZ E, QUAISER K. Panmyelopathy following epidemic hepatitis[J]. Wien Med Wochenschr,1955,105(1):19-22.
10 GONNOT M, NEUMANN F, HUET F, et al. Hepatitis-associated Aplastic Anemia[J]. J Pediatr Gastroenterol Nutr, 2022,75(5):553-555. doi:10.1097/mpg.0000000000003603
11 伍秋频,严士为,何筱胤,等. 儿童肝炎相关再生障碍性贫血2例及文献回顾[J]. 临床荟萃,2024,39(7):640-643.
12 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.
13 TüFEK?I ?, ?ZDEMIR H H, MALBORA B, et al. Hepatitis-Associated Aplastic Anemia: Etiology, Clinical Characteristics and Outcome[J]. J Pediatr Hematol Oncol, 2022,44(1):e223-223e226. doi:10.1097/mph.0000000000002268
14 王丽旻,闫建国,甘雨,等. 儿童不同临床分型药物性肝损害并发症及预后分析[J]. 中国肝脏病杂志,2022,14(4): 62-67.
15 GONNOT M, NEUMANN F, HUET F, et al. Hepatitis-associated Aplastic Anemia[J]. J Pediatr Gastroenterol Nutr, 2022,75(5):553-555. doi:10.1097/mpg.0000000000003603
16 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
17 杨文睿,井丽萍,周康,等. 41例肝炎相关再生障碍性贫血患者临床特征与免疫抑制治疗疗效观察[J]. 中华血液学杂志,2016,37(5):399-404.
18 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):e164-164e166. doi:10.1097/mph.0000000000001199
19 FU L, ZHANG J, WANG R, et al. Clinical characteristics of hepatitis-associated aplastic anemia in children[J]. Ann Hematol,2024,103(2):397-404. doi:10.1007/s00277-023-05566-y
20 梁笑楠,宋怡然,李周,等. 药物性肝损伤后肝炎相关再生障碍性贫血1例报告[J]. 临床肝胆病杂志,2020,36(8):1824-1826.
21 BABUSHOK D V, GRIGNON A L, 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
22 PATEL K R, BERTUCH A, SASA G S, et al. Features of Hepatitis in Hepatitis-associated Aplastic Anemia: Clinical and Histopathologic Study[J]. J Pediatr Gastroenterol Nutr, 2017,64(1):e7-7e12. doi:10.1097/mpg.0000000000001271
23 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
24 王彦,李佳.庞爱明,等. 异基因造血干细胞移植治疗肝炎相关性再生障碍性贫血28例疗效及安全性[J]. 中华血液学杂志,2023,44(8):628-634.
25 MORI T, ONISHI Y, OZAWA Y, et al. Outcome of allogeneic hematopoietic stem celltransplantation in adult patients with hepatitis-associated aplastic anemia[J]. Int J Hematol, 2019,109(6):711-717. doi:10.1007/s12185-019-02644-8
26 ZHANG X, YANG W, YANG D, et al. Comparison of hematopoietic stem cell transplantation and immunosuppressive therapy as the first-line treatment option for patients with severe hepatitis-associated aplastic anemia[J]. Front Immunol, 2023,14:1146997. doi:10.3389/fimmu.2023.1146997
27 ALTAY D, Y?LMAZ E, ?ZCAN A, et al. Hepatitis-associated aplastic anemia in pediatric patients: Single center experience[J]. Transfus Apher Sci, 2020,59(6):102900. doi:10.1016/j.transci.2020.102900
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