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