Outcomes of Severe Seronegative Hepatitis-associated Aplastic Anemia: A Pediatric Case Series. J Pediatr Gastroenterol Nutr 2021 Feb 01;72(2):194-201
Date
09/15/2020Pubmed ID
32925550Pubmed Central ID
PMC7856235DOI
10.1097/MPG.0000000000002940Scopus ID
2-s2.0-85099721796 (requires institutional sign-in at Scopus site) 10 CitationsAbstract
OBJECTIVES: Hepatitis-associated aplastic anemia (HAAA) is a potentially life-threatening diagnosis without clear treatment guidelines. The goal of the study was to characterize the presentation, evaluation, histopathology, and outcomes of therapy in children with HAAA to guide future research and to develop standardized care guidelines for this rare disease.
METHODS: Retrospective chart review of 4 patients with HAAA who presented to Children's Hospital Colorado between 2016 and 2019 was conducted. Patient presentation, evaluation, bone marrow and liver pathology, interventions, and clinical course were collected. Immunohistochemistry of liver biopsies was performed.
RESULTS: We treated 4 patients with HAAA without liver failure. All had evidence of systemic hyperinflammation and CD8+ T cell predominant liver tissue infiltration. One had a genetic mutation predisposing him to immune-mediated disease, but all other genetic testing was negative. In 3 of the 4 patients, hepatitis was poorly responsive to standard therapy with steroids, azathioprine, or tacrolimus; however, sustained biochemical remission of hepatitis was induced after more aggressive immunosuppressive therapies including Anti-Thymocyte Globulin (ATG) at standard immunosuppressive therapy (IST) dosing for severe Aplastic Anemia (sAA). Two patients underwent hematopoietic stem cell transplant (HSCT); 1 as first line therapy and 1 for refractory sAA.
CONCLUSIONS: We found that ATG-based IST induced remission of hepatitis in patients with steroid-refractory HAAA. This is also an appropriate initial treatment for severe Aplastic Anemia, though may not prevent the need for HSCT. We propose that equine ATG based IST at standard dosing regimen for sAA is a therapy that in select cases can be considered early on in the treatment course and could lead to a sustained remission of both hepatitis and sAA. This should be considered in collaboration with a pediatric hematologist.
Author List
Kemme S, Stahl M, Brigham D, Lovell MA, Nakano T, Feldman AG, Mack CAuthor
Cara Lynn Mack MD Chief, Professor in the Pediatrics department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Anemia, AplasticAnimals
Child
Colorado
Hepatitis
Horses
Humans
Immunosuppressive Agents
Male
Retrospective Studies
Tacrolimus
Treatment Outcome
