Novel protocol including liver biopsy to identify and treat CD8+ T-cell predominant acute hepatitis and liver failure

Pediatr Transplant. 2014 Aug;18(5):503-9. doi: 10.1111/petr.12296. Epub 2014 Jun 14.

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.

Keywords: acute hepatic failure; hepatitis-associated aplastic anemia; immune-mediated liver failure; immunohistochemistry.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Anemia, Aplastic / etiology
  • Anemia, Aplastic / therapy
  • Biopsy*
  • CD8-Positive T-Lymphocytes / cytology*
  • Child
  • Child, Preschool
  • Female
  • Hepatitis / immunology
  • Hepatitis / therapy*
  • Humans
  • Immunohistochemistry
  • Immunosuppression Therapy / adverse effects
  • Immunosuppressive Agents / therapeutic use
  • Inflammation
  • Liver / immunology
  • Liver / pathology*
  • Liver / surgery
  • Liver Failure, Acute / immunology
  • Liver Failure, Acute / therapy*
  • Liver Transplantation
  • Male
  • Retrospective Studies
  • Stem Cell Transplantation
  • Treatment Outcome

Substances

  • Immunosuppressive Agents