Hepatitis-Associated Aplastic Anemia in Children and Adolescents: A Comprehensive Review

Hepatitis-associated aplastic anemia (HAAA) is a rare but life-threatening subtype of acquired aplastic anemia (AA) that predominantly affects children and adolescents, characterized by bone marrow failure developing weeks to months following acute hepatitis. Although HAAA accounts for a small proportion of AA cases, it presents unique diagnostic and therapeutic challenges and remains poorly understood. Most cases are seronegative, with no identifiable viral pathogen, supporting an immune-mediated pathophysiology. Emerging evidence implicates dysregulated cytotoxic T-cell activation, reduced regulatory T-cell function, and a shared immune target within hepatic and hematopoietic tissues. HAAA follows a variable course of hepatitis and pancytopenia, which necessitates a high index of suspicion and thorough evaluation to exclude inherited and secondary causes of bone marrow failure. Management strategies are largely extrapolated from severe AA and include supportive care, immunosuppressive therapy with antithymocyte globulin and cyclosporine, and hematopoietic stem cell transplantation. While outcomes have improved with modern therapy, relapse, treatment failure, and clonal evolution remain challenges. This review synthesizes current knowledge on the epidemiology, pathophysiology, clinical features, diagnostic approach, treatment options, and outcomes of pediatric HAAA, highlighting critical gaps in evidence and the need for prospective studies to guide risk stratification and therapy optimization.