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Autoimmune hemolytic anemia (AIHA) with giant cell hepatitis (GCH) is an uncommon disease in children and is associated with an aggressive and often fatal course. The authors describe a 4-month-old girl who presented with AIHA and elevated liver enzymes. A liver biopsy was consistent with GCH. She was successfully treated with anti-CD20 antibody (rituximab)-containing therapy after failing initial immune suppression therapy. The authors also review the literature for similar cases.