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中国循证儿科杂志

中国循证儿科杂志 ›› 2024, Vol. 19 ›› Issue (6): 440-444.DOI: 10.3969/j.issn.1673-5501.2024.06.006

• 论著 • 上一篇    下一篇

巨肝细胞肝炎伴自身免疫性溶血性贫血23例病例系列报告

王妮1,6，李玉川2,6，张雪媛2，王彩红3，刘小乖4，林翊君5，陆怡2，谢新宝2   

  1. 1 遵义医科大学第三附属医院，遵义市第一人民医院儿科遵义，563000；2 复旦大学附属儿科医院感染传染科上海，201102；3 复旦大学附属儿科医院厦门分院，厦门市儿童医院感染科厦门，361006；4 西安交通大学附属儿童医院感染科西安，710003；5 福建省儿童医院消化科福州，350011；6 共同第一作者
  • 收稿日期:2024-11-26 修回日期:2024-12-21 出版日期:2024-12-25 发布日期:2024-12-25
  • 通讯作者: 谢新宝

A case series report on giant cell hepatitis associated with autoimmune hemolytic anemia: 23 cases

WANG Ni1,6, LI Yuchuan2,6, ZHANG Xueyuan2, WANG Caihong3, LIU Xiaoguai4, LIN Yijun5, LU Yi2, XIE Xinbao2   

  1. 1 Department of Pediatrics, The First People's Hospital of Zunyi City (The Third Affiliated Hospital of Zunyi Medical University), Zunyi 563000, China; 2 Department of Infectious Diseases,The Children' s Hospital, Fudan University,Shanghai 201102, China; 3 Department of Infectious Diseases, Xiamen Children's Hospital, Children's Hospital of Fudan University at Xiamen, Xiamen 361006, China; 4 Department of Infectious Diseases, Xi'an Jiaotong University Affiliated Children's Hospital, Xi'an 710003, China; 5 Department of Pediatrics, Fujian Children's Hospital (Fujian Branch of Shanghai Children's Medical Center), Fuzhou 350011, China; 6 Co-first author
  • Received:2024-11-26 Revised:2024-12-21 Online:2024-12-25 Published:2024-12-25
  • Contact: XIE Xinbao

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摘要： 背景巨肝细胞肝炎伴自身免疫性溶血性贫血（GCH-AHA)是一种罕见的免疫介导的疾病，常常婴幼儿期发病，既往文献报道预后较差，目前无统一的治疗方案。 目的探讨GCH-AHA患儿的临床特征、治疗和预后，提高对该病的认识和诊治水平。 设计病例系列报告。 方法回顾性分析2013年1月至2024年9月多中心诊治、随访的23例GCH-AHA患儿的临床特征、治疗及预后资料。以巨细胞肝炎伴自身免疫性溶血性贫血和Giant cell hepatitis with autoimmune hemolytic anemia为中英文关键词检索中英文数据库，检索时间为自建库至2024年12月10日。 主要结局指标GCH-AHA临床特征、治疗和预后情况。 结果23例GCH-AHA患儿中男15例，女8例，平均发病年龄7.8（6.8，10.5）月龄，5～12月起病18例。以皮肤苍黄为主要起病形式19例，其中11例伴发热。所有患儿均Coombs试验阳性、免疫性溶血性贫血、肝功能异常、肝病理巨肝细胞转化。23例患儿随访时间12~137个月，均予糖皮质激素治疗，起始剂量甲泼尼龙每天2~4 mg·kg-1，根据病情逐渐减量；18例联合硫唑嘌呤，5例患儿起始糖皮质激素联合吗替麦考酚酯或环孢素或他克莫司治疗；19例患儿因病情严重或反复应用≥1次的IVIG 2 g·kg-1；12例患儿因病情严重或反复给予利妥昔单抗治疗。 10例患儿治愈停药；12例患儿缓解单药维持治疗，1例患儿因肝衰竭合并感染死亡。文献复习纳入27项研究（含本文）共89例GCH-AHA患儿，多在1岁以内起病，均Coombs试验阳性，肝脏病理巨肝细胞改变，96.8%患儿网织红细胞升高，97.8%患儿转氨酶中重度升高。18例（20.2%）死亡。 结论婴幼儿表现为自身免疫性溶血和急性肝病时，需考虑 GCH-AHA可能，需及时完善肝组织病理检查进一步确诊。糖皮质激素和硫唑嘌呤是治疗儿童GCH-AHA的首选药物，难治性GCH-AHA用利妥昔单抗治疗可改善预后。GCH-AHA患儿经免疫抑制剂治疗大部分预后良好。

关键词: 巨肝细胞肝炎, 自身免疫性溶血性贫血, GCH-AHA, 特点, 预后

Abstract: BackgroundGiant cell hepatitis associated with autoimmune hemolytic anemia (GCH-AHA) is a rare immune-mediated disease that often occurs in infants and young children. Previous literature reports suggest a poor prognosis, and there is currently no unified treatment protocol. ObjectiveTo explore the clinical features, treatment, and prognosis of children with GCH-AHA, and to improve the understanding and diagnosis and treatment of this disease. DesignCase series report. Methods A retrospective analysis was conducted on the clinical features, treatment, and prognosis of 23 children with GCH-AHA who were diagnosed and followed up at multiple centers from January 2013 to September 2024. Chinese and English databases were searched using the keyword "Giant cell hepatitis with autoimmune hemolytic anemia," with the search period ranging from the establishment of the databases to December 10, 2024. Main outcome measuresClinical features, treatment, and prognosis of GCH-AHA. ResultsAmong the 23 children, 15 were male and 8 were female, with an average onset age of 7.8 (6.8, 10.5) months. Eighteen cases had an onset between 5 and 12 months. The primary presenting symptom was pale yellow skin (19 cases), with 11 cases accompanied by fever. All 23 children met the diagnostic criteria for GCH-AHA, including Coombs-positive immune hemolytic anemia, abnormal liver function, and giant cell transformation on liver histopathology. The follow-up period ranged from 12 to 137 months. All children received glucocorticoid treatment, with an initial dose of methylprednisolone at 2-4 mg·kg-1·d-1, gradually tapered based on the condition. Eighteen cases were treated with azathioprine, and 5 cases received initial glucocorticoid treatment combined with mycophenolate mofetil, cyclosporine, or tacrolimus. Nineteen children received IVIG at 2 g·kg-1 once or more due to severe or recurrent disease. Twelve children received rituximab treatment at 375 mg·m-2 weekly. Ten children were cured and discontinued treatment, 12 children achieved remission and were maintained on monotherapy, and 1 child died due to liver failure combined with infection. The literature review included 27 studies (including this one) with a total of 89 GCH-AHA cases. Most children developed the disease within the first year of life. All children had positive Coombs tests, giant cell changes on liver pathology, 96.8% had elevated reticulocytes, and 97.8% had moderate to severe elevation of transaminases. 18 children (20.2%) died. ConclusionWhen infants and young children present with autoimmune hemolysis and acute liver disease, GCH-AHA should be considered, and liver histopathology should be ly performed for confirmation. Glucocorticoids and azathioprine are the first-line treatments for GCH-AHA in children, and rituximab can improve the prognosis in refractory cases. Most children with GCH-AHA have a good prognosis with immunosuppressive treatment.

Key words: Giant cell hepatitis, Autoimmune hemolytic anemia, GCH-AHA, Feature, Prognosis