TY - JOUR
T1 - Hepatic Encephalopathy in Children with Acute Liver Failure
T2 - Utility of Serum Neuromarkers
AU - Pediatric Acute Liver Failure Study Group
AU - Toney, Nicole A.
AU - Bell, Michael J.
AU - Belle, Steven H.
AU - Hardison, Regina M.
AU - Rodriguez-Baez, Norberto
AU - Loomes, Kathleen M.
AU - Vodovotz, Yoram
AU - Zamora, Ruben
AU - Squires, Robert H.
N1 - Funding Information:
Hospital of Pittsburgh of UPMC 4401 Penn Ave, Faculty Pavilion Room 6116, Pittsburgh, PA 15224 (e-mail: squiresr@upmc.edu). Laboratory analysis was performed at the University of Pittsburgh. Supplemental digital content is available for this article. Direct URL citations appear in the printed text, and links to the digital files are provided in the HTML text of this article on the journal’s Web site (www.jpgn.org). Funding for the project is provided by the National Institutes of Health (NIH-NIDDK U01 DK072146). The authors report no conflicts of interest. Copyright © 2019 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition DOI: 10.1097/MPG.0000000000002351
Funding Information:
Acknowledgments: Key individuals who have actively participated in the PALF studies include (by site): Current Sites, Principal Investigators and Coordinators—Robert H. Squires, MD, Kathryn Bukauskas, RN, CCRC, Madeline Schulte, RN, BSN, Clinical Research Coordinator (Children’s Hospital of Pittsburgh of UPMC, Pittsburgh, Pennsylvania); Michael R. Narkewicz, MD, Michelle Hite, MA, CCRC (Children’s Hospital Colorado, Aurora, Colorado); Kathleen M. Loomes, MD, Elizabeth B. Rand, MD, David Piccoli, MD, Deborah Kawchak, MS, RD, Christa Seidman, Clinical Research Coordinator (Children’s Hospital of Philadelphia, Philadelphia, PA); Rene Romero, MD, Saul Karpen, MD, PhD, Liezl de la Cruz-Tracy, CCRC (Emory University, Atlanta, GA); Vicky Ng, MD, Kelsey Hunt, Clinical Research Coordinator (Hospital for Sick Children, Toronto, Ontario, Canada); Girish C. Subbarao, MD, Ann Klipsch, RN, Sarah Munson, Clinical Research Coordinator (Indiana University Riley Hospital, Indianapolis, IN); Estella M. Alonso, MD, Lisa Sorenson, PhD, Susan Kelly, RN, BSN, Katie Neighbors, MPH, CCRC (Lurie Children’s Hospital of Chicago, Chicago, IL); Philip J. Rosenthal, MD, Shannon Fleck, Clinical Research Coordinator (University of California San Francisco, San Francisco, CA); Mike A. Leonis, MD, PhD, John Bucuvalas, MD, Tracie Horning, Clinical Research Coordinator (University of Cincinnati, Cincinnati, OH); Norberto Rodriguez Baez, MD, Shirley Montanye, RN, Clinical Research Coordinator, Margaret Cowie, Clinical Research Coordinator (University of Texas Southwestern, Dallas, TX); Simon P. Horslen, MD, Karen Murray, MD, Melissa Young, Clinical Research Coordinator, Heather Nielson, Clinical Research Coordinator, Jani Klein, Clinical Research Coordinator (University of Washington, Seattle, WA); David A. Rudnick, MD, PhD, Ross W. Shepherd, MD, Kathy Harris, Clinical Research Coordinator (Washington University, St. Louis, MO). Previous Sites, Principal Investigators and Coordinators – Saul J. Karpen, MD, PhD, Alejandro De La Torre, Clinical Research Coordinator (Baylor College of Medicine, Houston, TX); Dominic Dell Olio, MD, Deirdre Kelly, MD, Carla Lloyd, Clinical Research Coordinator (Birmingham Children’s Hospital, Birmingham, United Kingdom); Steven J. Lobritto, MD, Sumerah Bakhsh, MPH, Clinical Research Coordinator (Columbia University, New York, NY); Maureen Jonas, MD, Scott A. Elifoson, MD, Roshan Raza, MBBS (Harvard Medical School, Boston, MA); Kathleen B. Schwarz, MD, Wikrom W. Karnsakul, MD, Mary Kay Alford, RN, MSN, CPNP (Johns Hopkins University, Baltimore, MD); Anil Dhawan, MD, Emer Fitzpatrick, MD (King’s College Hospital, London, United Kingdom); Nanda N. Kerkar, MD, Brandy Haydel, CCRC, Sreevidya Narayanappa, Clinical Research Coordinator (Mt. Sinai School of Medicine, New York, NY); M. James Lopez, MD, PhD, Victoria Shieck, RN, BSN (University of Michigan, Ann Arbor, MI). The authors are also grateful for support from the National Institutes of Health (Edward Doo, MD, Director Liver Disease Research Program, and Averell H. Sherker, MD, Scientific Advisor, Viral Hepatitis and Liver Diseases, DDDN-NIDDK) and for assistance from members of the Data Coordinating Center at the University of Pittsburgh (directed by Steven H. Belle, PhD, MScHyg).
Publisher Copyright:
Copyright © 2019 ESPGHAN and NASPGHAN. All rights reserved.
PY - 2019/7/1
Y1 - 2019/7/1
N2 - 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.
AB - 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.
KW - acute liver failure
KW - hepatic encephalopathy
KW - inflammatory markers
KW - neuromarkers
KW - pediatric acute liver failure
UR - http://www.scopus.com/inward/record.url?scp=85068587867&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85068587867&partnerID=8YFLogxK
U2 - 10.1097/MPG.0000000000002351
DO - 10.1097/MPG.0000000000002351
M3 - Article
C2 - 31058776
AN - SCOPUS:85068587867
SN - 0277-2116
VL - 69
SP - 108
EP - 115
JO - Journal of pediatric gastroenterology and nutrition
JF - Journal of pediatric gastroenterology and nutrition
IS - 1
ER -