Hepatitis-associated Aplastic Anemia in Children: Unraveling Clinical Mysteries in a Single-center Case Series–More Questions Than Answers!

Hepatitis-associated aplastic anemia (HAAA) is a rare but potentially life-threatening form of acquired aplastic anemia. Since 2022, our center has observed an increase in HAAA cases. This study examines pediatric HAAA cases to enhance understanding of its presentation, diagnosis, and treatment outcomes, aiming to guide future research and care protocols. A retrospective review was conducted on 5 pediatric HAAA patients treated between 2022 and 2023 at a tertiary children's hospital in the Midwestern United States. Data included clinical presentation, diagnostics, bone marrow and liver pathology, treatments, and clinical course. Immunohistochemical analysis was performed on liver biopsies. As a result, none of the 5 patients developed liver failure. One patient had a genetic mutation associated with an immune-mediated disease; other genetic tests were negative. Histopathology revealed consistent CD8 T-cell infiltration in the liver and bone marrow, with a median CD4/CD8 ratio of 0.5. The median interval from hepatitis onset to pancytopenia was 7 to 9 weeks, with a median follow-up of 2.5 years. Four patients developed severe aplastic anemia (sAA), and 1 had nonsevere aplastic anemia (NSAA). Steroid therapy was insufficient in 4 cases, necessitating antithymocyte globulin (ATG) and cyclosporine. Due to nonresponse, 4 patients required stem cell transplantation (SCT). HAAA can rapidly progress to sAA, highlighting the importance of early, aggressive intervention. Equine ATG and cyclosporine should be initiated promptly, but refractory cases often require SCT. Further research is essential to refine therapeutic strategies and improve outcomes.