Acute severe cholestatic hepatitis and lymphopenia characterize pediatric hepatitis-associated aplastic anemia.

OBJECTIVES

Hepatitis-associated aplastic anemia (HAAA) is described as acute severe hepatitis of unknown origin followed by bone marrow failure (BMF). We aimed to provide a comprehensive picture of pediatric HAAA.

METHODS

Two-center retrospective analysis was performed using data from children diagnosed with acquired BMF, including severe aplastic anemia (SAA) and myelodysplastic syndrome type refractory cytopenia of childhood (RCC). The assessment of the subcohort of HAAA included clinical features indicative of diagnosis and disease progression, with additional data from previously published case series.

RESULTS

Cohort comprised 62 children with acquired BMF and 22 children with HAAA. Median age of HAAA patients was 13.5 years. Potentially triggering viral infections were detected in 45%. The median interval from hepatitis onset to cytopenia was 3 weeks. All cases presented with severe hepatitis (median alanine transaminase 2127 U/L) and all but one with hyperbilirubinemia (median bilirubin 15.3 mg/dL). Coagulopathy was variable (median international normalized ratio 1.5). Four patients (18%) developed acute liver failure, two (9%) required liver transplantation. Hepatic parameters normalized within a median of 8.5 weeks. There was no statistically significant difference in the course of hepatitis between patients with SAA and RCC. Early lymphopenia was a key finding in patients with HAAA, progressing from a median of 905/µL at hepatitis onset to 530/µL within 4 weeks.

CONCLUSIONS

HAAA occurs in both SAA and RCC. Most cases present with severe acute cholestatic hepatitis and variable coagulopathy. Hepatic recovery is common. Lymphopenia at disease onset is frequent and may serve as a diagnostic marker.