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Case Series: Anti-Thymocyte Globulin as a Treatment for Steroid-Refractory Severe Acute Hepatitis in Children

A. L. Peters, A. Miethke, K. Campbell

Department of Pediatrics, Division of Pediatric Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center, Cincinnati, OH

Meeting: 2019 American Transplant Congress

Abstract number: C303

Keywords: Antilymphocyte antibodies, CD3, Hepatitis, Liver failure

Session Information

Session Name: Poster Session C: Liver: Pediatrics

Session Type: Poster Session

Date: Monday, June 3, 2019

Session Time: 6:00pm-7:00pm

 Presentation Time: 6:00pm-7:00pm

Location: Hall C & D

*Purpose: Pediatric severe acute hepatitis (SAH), when not attributed to acetaminophen toxicity, is commonly hypothesized to be caused by a non-typeable viral infection and/or immune dysregulation. While steroids are frequently used as a rescue therapy for SAH, little data exists on the use of biologic therapies for steroid-refractory cases. T cell directed therapies, including anti-thymocyte globulin (ATG), have a long history of use in a variety of immune-mediated disorders, including acute hepatitis associated aplastic anemia, graft versus host disease, and solid organ transplantation, but have not been described in steroid-refractory SAH.

*Methods: Retrospective chart review was performed on two pediatric patients who presented to Cincinnati Children’s Hospital Medical Center in 2018 with steroid-refractory, non-viral, non-acetaminophen SAH.

*Results: We report the clinical course of two children with steroid-refractory SAH who were successfully treated with ATG. The patients were both male, age 8 and 9 years old respectively, who presented with jaundice and severe cholestatic hepatitis preceded by low grade fever and vomiting. Routine molecular and serological studies for viral and autoimmune hepatitis were negative. Both children had evidence of immune dysregulation including decreased NK cell function, elevated plasma soluble IL-2 receptor and soluble CD163. Percutaneous liver biopsy specimens obtained from both patients showed severe mixed lymphocytic portal infiltrates comprised primarily of CD3+CD8+T cells. After excluding active viral infection, patients were treated with high dose IV methylprednisolone initially at 2mg/kg/day, with maximum dosing up to 10mg/kg/day with only minimal improvement. When the patients did not improve with high dose steroids, they each received rabbit ATG 1.5mg/kg/day for 7d with excellent biochemical response. Patient 1 was readmitted for severe influenza infection, and Patient 2 was readmitted for serum sickness 10 days after the last dose of ATG. LFTs normalized in both patients at ~3 months post-ATG and remained normal. Patient 1 was treated with low dose prednisone and Imuran, both of which were discontinued at 11 months post-presentation due to low lymphocyte counts. Patient 2 was treated with low dose prednisone and tacrolimus for maintenance immunosuppression, but developed evidence of aplastic anemia approximately 7 months post-presentation. Patient 1 developed chronic hypogammaglobulinemia and receives monthly IVIg infusions.

*Conclusions: ATG should be considered as a possible treatment for steroid-refractory seronegative SAH in children, and may delay onset of hepatitis-associated aplastic anemia. Further studies are needed to determine whether ATG prevents chronic liver fibrosis and to document potential adverse immune and infectious complications.

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To cite this abstract in AMA style:

Peters AL, Miethke A, Campbell K. Case Series: Anti-Thymocyte Globulin as a Treatment for Steroid-Refractory Severe Acute Hepatitis in Children [abstract]. Am J Transplant. 2019; 19 (suppl 3). https://atcmeetingabstracts.com/abstract/case-series-anti-thymocyte-globulin-as-a-treatment-for-steroid-refractory-severe-acute-hepatitis-in-children/. Accessed May 9, 2025.

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