Insights into Hepatitis-Associated Aplastic Anemia in Pediatric Patients: A Comprehensive Case Series

Introduction

Hepatitis-associated aplastic anemia (HAAA) is a rare and life-threatening condition in pediatric patients characterized by pancytopenia with hypoplastic bone marrow following an episode of hepatitis. HAAA is observed in approximately 1% to 5% of all newly diagnosed cases of acquired aplastic anemia. Despite its rarity, HAAA poses significant diagnostic and therapeutic challenges which in some cases require prolonged and vigilant monitoring. This study presents a comprehensive case series from a single institution involving five pediatric patients aged 18 months to 12 years diagnosed with HAAA. Clinical presentations included severe pancytopenia, jaundice, and elevated liver enzymes in all patients. Detailed analysis of diagnostic evaluations, treatment regimens, complications, and outcomes were conducted. Given the limited number of cases reported in the literature, there is a significant need for additional studies to better understand the disease process and to develop standardized diagnostic and therapeutic approaches.

Methods

This case series involves a thorough review of five pediatric patients diagnosed with HAAA at a single institution over a two-year period. Comprehensive diagnostic workups were conducted for each patient, including genetic, nutritional, immune, bone marrow, and infectious evaluations.

Results

The five pediatric patients (3 females and 2 males) presented with severe pancytopenia, jaundice, and elevated liver enzymes following an episode of hepatitis. The duration between hepatitis and diagnosis of HAAA averaged 2.4 months (ranging from 1 day to 159 days) which is similar to what has been described historically. Despite extensive diagnostic evaluations including liver function tests, liver imaging and in some cases liver biopsies, there was no appreciable cause for hepatitis such as infection. All patients were placed on prophylactic antifungal, antibacterial and antiviral as supportive measures due to the high risk of infection.

Genetic evaluations did not reveal any germline mutation for any of the patients. However, the identification of various variants of uncertain relevance (VUR) including a CASP10 VUR in one patient presents a particular challenge, as the clinical significance of VURs remains unclear, complicating clinical decision-making.

Some patients exhibited unique and complex presentations. One 2-year-old girl presented with severe pancytopenia and hepatitis and was diagnosed with HAAA. She underwent BMT after failing IST, facing complications such as CMV viremia and Clostridium difficile enteritis but successfully engrafted and stabilized post-transplant. Another 4-year-old boy with markedly elevated liver enzymes and suspected Wilson's disease failed immunosuppressive therapy (IST) and faced severe fungal infection, leading to an urgent syngeneic transplant from his identical twin. Post-transplant complications included bacteremia, yet he eventually stabilized. An 18-month-old girl was initially diagnosed with Evan's syndrome which proved to be refractory to steroids, and immunosuppression. After an unexplained episode of hepatitis, worsening pancytopenia prompted a repeat bone marrow evaluation which was consistent with severe aplastic anemia. Despite undergoing BMT, she developed post-transplant lymphoproliferative disorder (PTLD) and succumbed to the condition raising concern for an underlying immune dysregulation.

Discussion

This case series adds to the limited literature on pediatric HAAA, illustrating the significant diagnostic and therapeutic challenges associated with this condition. The complexity of HAAA necessitates a multidisciplinary approach. Our bone marrow failure team, which includes specialists in genetics, hematology, oncology, and Bone marrow transplant (BMT), works closely with hepatology, and pathology to provide comprehensive and coordinated care. This collaborative approach is crucial for managing the intricate needs of HAAA patients and improving their outcomes.

Conclusion

The rarity of HAAA contributes to the lack of standardized diagnostic and therapeutic approaches, making this case series a crucial addition to the existing literature. By documenting these cases, we aim to provide valuable insights that can help in the management and understanding of this rare condition, ultimately improving patient outcomes.

Maese:Jazz pharmaceuticals: Consultancy, Speakers Bureau; Servier: Membership on an entity's Board of Directors or advisory committees.