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

BACKGROUND: 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. CASE PRESENTATION: 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. CONCLUSIONS: 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.