Immunophenotype Predicts Outcome in Pediatric Acute Liver Failure

Bucuvalas, John*; Filipovich, Lisa; Yazigi, Nada*; Narkewicz, Michael R.; Ng, Vicky§; Belle, Steven H.||; Zhang, Song||; Squires, Robert H.

Journal of Pediatric Gastroenterology & Nutrition:
doi: 10.1097/MPG.0b013e31827a78b2
Original Articles: Hepatology and Nutrition
Abstract

Objectives: We sought to determine whether markers of T-cell immune activation, including soluble interleukin 2 receptor alpha (sIL2Rα) levels predict outcome in pediatric acute liver failure and may target potential candidates for immunomodulatory therapy.

Methods: We analyzed markers of immune activation in 77 patients with pediatric acute liver failure enrolled in a multinational, multicenter study. The outcomes were survival with native liver, liver transplantation (LT), and death without transplantation within 21 days after enrollment.

Results: Adjusting for multiple comparisons, only normalized serum sIL2Rα level differed significantly among the 3 outcomes, and was significantly higher in patients who died (P = 0.02) or underwent LT (P = 0.01) compared with those who survived with their native liver. The 37 patients with normal sIL2Rα levels all lived, 30 with their native liver. Of the 15 subjects with markedly high sIL2Rα (≥5000 IU/mL), 5 survived with their native liver, 2 died, and 8 underwent LT.

Conclusions: Evidence of immune activation is present in some patients who die or undergo LT. Patients with higher sIL2Rα levels were more likely to die or undergo LT within 21 days than those with lower levels. Identifying a subset of patients at risk for poor outcome may form the foundation for targeted clinical trials with immunomodulatory drugs.

Author Information

*Division of Gastroenterology, Hepatology and Nutrition

Division of Bone Marrow Transplantation and Immunodeficiency, Cincinnati Children's Hospital, Cincinnati, OH

Department of Pediatrics, Section of Pediatric Gastroenterology, Hepatology and Nutrition, University of Colorado School of Medicine and Children's Hospital Colorado, Aurora, CO

§Division of Gastroenterology, Hepatology and Nutrition, Hospital for Sick Children, Toronto, ON, Canada

||Department of Epidemiology

Division of Gastroenterology, Hepatology and Nutrition, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, PA.

Address correspondence and reprint requests to John C. Bucuvalas, MD, Professor of Pediatrics, Cincinnati Children's Hospital Medical Center, 3333 Burnet Ave, Cincinnati, OH 45229 (e-mail: john.bucuvalas@cchmc.org).

Received 6 August, 2012

Accepted 22 October, 2012

Supported by the Division of Digestive Diseases and Nutrition within the National Institute of Diabetes and Digestive and Kidney (NIDDK) Diseases of the National Institute of Health (NIH) (5U01 DK072146) and NIH/NCRR Colorado CTSI Grant Number UL1 RR025780. Contents are the authors’ sole responsibility and do not necessarily represent official NIH views.

The authors report no conflicts of interest.

Copyright 2013 by ESPGHAN and NASPGHAN