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Hepatic Encephalopathy in Children with Acute Liver Failure – Utility of Serum Neuromarkers

Toney, Nicole A., MPH*; Bell, Michael J., MD*; Belle, Steven H., PhD; Hardison, Regina M., MS; Rodriguez-Baez, Norberto, MD; Loomes, Kathleen M., MD§; Vodovotz, Yoram, PhD; Zamora, Ruben, PhD; Squires, Robert H., MD|| for the Pediatric Acute Liver Failure Study Group

Journal of Pediatric Gastroenterology and Nutrition: April 15, 2019 - Volume Publish Ahead of Print - Issue - p
doi: 10.1097/MPG.0000000000002351
Original Article: Hepatology: PDF Only

Background: Pediatric acute liver failure (PALF) is a public heath burden, often requiring prolonged hospitalization and liver transplantation. Hepatic encephalopathy (HE) is a complication of PALF with limited diagnostic tools to predict outcomes. Serum neurological markers (neuron specific enolase (NSE), S100β, and myelin basic protein (MBP)) can be elevated in traumatic or ischemic brain injury. We hypothesized that these neuromarkers would be associated with the development of HE in PALF.

Methods: PALF study participants enrolled between May 2012 and December 2014 by 12 participating centers were the subjects of this analysis. Daily HE assessments were determined by study investigators. Neurological and inflammatory markers were measured using ELISA and MILLIPLEX techniques, respectively. To model encephalopathy, these markers were log2 transformed and individually examined for association with HE using a generalized linear mixed model with a logit link and random intercept.

Results: 82 children had neurological and inflammatory marker levels and HE assessments recorded, with the majority having assessments for 3 days during their illness. An indeterminate diagnosis (29%) was most common and the median age was 2.9 years. Significant associations were observed for HE with S100β (OR 1.16, 95% CI [1.03–1.29], p = 0.04) and IL-6 (OR 1.24 [1.11–1.38], p = 0.006).

Conclusion: Serum S100β and IL-6 are associated with HE in children with PALF. Measuring these markers may assist in assessing neurological injury in PALF, impacting clinical decisions.

*Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA, United States

School of Public Health, University of Pittsburgh, Pittsburgh, PA, United States

Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, University of Texas Southwestern Medical Center, Children's Health, Dallas TX, United States

§Division of Gastroenterology, Hepatology and Nutrition, The Children's Hospital of Philadelphia Department of Pediatrics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, United States

Department of Surgery, University of Pittsburgh, Pittsburgh, PA, United States

||Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, University of Pittsburgh School of Medicine, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, PA, United States.

Address correspondence and reprint requests to Robert H. Squires, MD, Gastroenterology/Hepatology/Nutrition, Children's Hospital of Pittsburgh of UPMC 4401 Penn Avenue, Faculty Pavilion Room 6116 Pittsburgh, PA 15224 (e-mail:

Received 20 June, 2018

Accepted 14 March, 2019

Laboratory analysis was performed at the University of Pittsburgh.

Financial Support: NIH/NIDDK (UO1-DK072146).

The authors report no conflicts of interest.

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© 2019 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology,