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Published on: February 19, 2019
Novel protocol including liver biopsy to identify and treat CD8+ T-cell predominant acute hepatitis and liver failure
Rebecca B McKenzie1, William E Berquist, Kari C Nadeau
1Division of Gastroenterology, Hepatology & Nutrition, Department of Pediatrics, Stanford School of Medicine, Stanford, CA, USA.
Insights
Immune dysregulation may cause acute liver failure in children. Treating pediatric patients with immune therapy improved transplant-free survival, but some developed bone marrow failure.
Area of Science:
- Pediatric Hepatology
- Immunology
- Gastroenterology
Background:
- Acute liver failure (ALF) in children often has unknown causes, frequently necessitating liver transplantation.
- Immune dysregulation is increasingly recognized as a potential etiology for indeterminate acute hepatitis and liver failure in pediatric populations.
Purpose of the Study:
- To investigate immune-mediated acute liver injury in children.
- To evaluate the efficacy of a multidisciplinary clinical protocol for diagnosing and treating immune-mediated acute liver injury in pediatric patients.
Main Methods:
- Nine pediatric patients with inflammation and no active infection on liver biopsy were treated with intravenous immune globulin and methylprednisolone.
- Immune markers and liver injury patterns (CD8+ T-cell predominance) were assessed.
- Treatment response and outcomes, including transplant-free survival and development of bone marrow failure, were monitored.
Main Results:
- Seven patients exhibited positive immune markers.
- All patients demonstrated CD8+ T-cell predominant liver injury, responding to immune therapy.
- Five patients achieved liver function recovery without transplantation; three later developed bone marrow failure.
Conclusions:
- A tissue-based diagnostic and treatment approach for immune-mediated acute liver injury in children can improve transplant-free survival.
- Further research is needed to characterize immune injury and identify patients at risk for bone marrow failure who may benefit from intensified immunosuppression.
Abstract:
In the majority of children with ALF, the etiology is unknown and liver transplantation is often needed for survival. A patient case prompted us to consider that immune dysregulation may be the cause of indeterminate acute hepatitis and liver failure in children. Our study includes nine pediatric patients treated under a multidisciplinary clinical protocol to identify and treat immune-mediated acute liver injury. Patients with evidence of inflammation and no active infection on biopsy received treatment with intravenous immune globulin and methylprednisolone. Seven patients had at least one positive immune marker before or after treatment. All patients had a CD8+ T-cell predominant liver injury that completely or partially responded to immune therapy. Five of the nine patients recovered liver function and did not require liver transplantation. Three of these patients subsequently developed bone marrow failure and were treated with either immunosuppression or stem cell transplant. This series highlights the importance of this tissue-based approach to diagnosis and treatment that may improve transplant-free survival. Further research is necessary to better characterize the immune injury and to predict the subset of patients at risk for bone marrow failure who may benefit from earlier and stronger immunosuppressive therapy.
