Late-onset combined immunodeficiency and bone marrow failure in severe autoimmune hepatitis: a case report

Late-onset combined immunodeficiency ( is a rare primary immunodeficiency characterized by hypogammaglobulinemia, T-cell lymphopenia, and susceptibility to opportunistic infections. While autoimmune liver involvement has been well documented in common variable immunodeficiency, no association with late-onset combined immunodeficiency has previously been reported. This case represents, to our knowledge, the first pediatric description of autoimmune hepatitis as the initial manifestation of late-onset combined immunodeficiency.

We present the case report of a 15-year old North African Arabic Tunisian boy. A 15-year-old boy presented with severe hepatitis, clinically and histologically consistent with seronegative autoimmune hepatitis. Corticosteroid therapy led to clinical improvement and enabled a liver biopsy, which confirmed autoimmune hepatitis. Persistent hypogammaglobulinemia and lymphopenia involving T, B, and NK cells prompted further immunologic evaluation, confirming the diagnosis of late-onset combined immunodeficiency. The disease course was complicated by hepatitis-associated aplastic anemia and hemorrhagic events. Despite hematopoietic stem cell transplantation, the patient died from septic complications.

This case highlights the importance of screening for underlying immunodeficiency in adolescents presenting with atypical or seronegative autoimmune hepatitis. Early recognition of late-onset combined immunodeficiency and related complications, such as hepatitis-associated aplastic anemia, is crucial for timely multidisciplinary management and may significantly impact patient outcomes.