Hepatic Encephalopathy in Children With Acute Liver Failure: Utility of Serum Neuromarkers

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,...

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Published inJournal of pediatric gastroenterology and nutrition Vol. 69; no. 1; pp. 108 - 115
Main Authors Toney, Nicole A, Bell, Michael J, Belle, Steven H, Hardison, Regina M, Rodriguez-Baez, Norberto, Loomes, Kathleen M, Vodovotz, Yoram, Zamora, Ruben, Squires, Robert H
Format Journal Article
LanguageEnglish
Published United States by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology 01.07.2019
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Abstract 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, S100β, and myelin basic protein) 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 enzyme-linked immunosorbent assay 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:Eighty-two 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 (odds ratio 1.16, 95% confidence interval [1.03–1.29], P = 0.04) and IL-6 (odds ratio 1.24 [1.11–1.38], P = 0.006). CONCLUSIONS: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.
AbstractList 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, S100β, and myelin basic protein) can be elevated in traumatic or ischemic brain injury. We hypothesized that these neuromarkers would be associated with the development of HE in PALF. 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 enzyme-linked immunosorbent assay 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. Eighty-two 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 (odds ratio 1.16, 95% confidence interval [1.03-1.29], P = 0.04) and IL-6 (odds ratio 1.24 [1.11-1.38], P = 0.006). 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.
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, S100β, and myelin basic protein) 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 enzyme-linked immunosorbent assay 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:Eighty-two 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 (odds ratio 1.16, 95% confidence interval [1.03–1.29], P = 0.04) and IL-6 (odds ratio 1.24 [1.11–1.38], P = 0.006). CONCLUSIONS: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.
BACKGROUNDPediatric 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, S100β, and myelin basic protein) can be elevated in traumatic or ischemic brain injury. We hypothesized that these neuromarkers would be associated with the development of HE in PALF. METHODSPALF 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 enzyme-linked immunosorbent assay 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. RESULTSEighty-two 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 (odds ratio 1.16, 95% confidence interval [1.03-1.29], P = 0.04) and IL-6 (odds ratio 1.24 [1.11-1.38], P = 0.006). CONCLUSIONSSerum 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.
Author Vodovotz, Yoram
Hardison, Regina M
Bell, Michael J
Loomes, Kathleen M
Toney, Nicole A
Belle, Steven H
Zamora, Ruben
Rodriguez-Baez, Norberto
Squires, Robert H
AuthorAffiliation Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, University of Texas Southwestern Medical Center, Childrenʼs Health, Dallas, TX
School of Public Health, University of Pittsburgh, Pittsburgh, PA
Critical Care Medicine
Division of Gastroenterology, Hepatology and Nutrition, The Childrenʼs Hospital of Philadelphia Department of Pediatrics, University of Pennsylvania Perelman School of Medicine, Philadelphia
Department of Surgery, University of Pittsburgh
Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, University of Pittsburgh School of Medicine, Childrenʼs Hospital of Pittsburgh of UPMC, Pittsburgh, PA
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    fullname: Whitington PF
– ident: e_1_2_10_9_2
  doi: 10.1126/scitranslmed.3003748
– ident: e_1_2_10_28_2
  doi: 10.1007/BF00689509
– ident: e_1_2_10_4_2
  doi: 10.1002/j.1536-4801.2002.tb07745.x
– ident: e_1_2_10_26_2
  doi: 10.1056/NEJMra1600561
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Snippet BACKGROUND:Pediatric acute liver failure (PALF) is a public heath burden, often requiring prolonged hospitalization and liver transplantation. Hepatic...
Pediatric acute liver failure (PALF) is a public heath burden, often requiring prolonged hospitalization and liver transplantation. Hepatic encephalopathy (HE)...
BACKGROUNDPediatric acute liver failure (PALF) is a public heath burden, often requiring prolonged hospitalization and liver transplantation. Hepatic...
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Title Hepatic Encephalopathy in Children With Acute Liver Failure: Utility of Serum Neuromarkers
URI https://www.ncbi.nlm.nih.gov/pubmed/31058776
https://search.proquest.com/docview/2232129148
https://pubmed.ncbi.nlm.nih.gov/PMC6591057
Volume 69
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