? The Pediatric Acute Liver Failure Study Group (PALFSG) is the first multi-center, multi-national collaboration to identify, characterize, and develop management strategies for infants, children and adolescents who present with acute liver failure (ALF). Initial funding and support came through the Acute Liver Failure Study Group (NIH 1R01-DK58369-01, William Lee, MD, P.I). This proposal is to establish independent NIH funding to support the current and future activities of this pediatric consortium. PALFSG includes 24 active sites (21 in the U.S., 1 in Canada and 2 in the U.K.) which have collected detailed clinical data from 293 children. We have already redefined ALF in children, demonstrated that the etiologies of ALF in children differs greatly from those seen in adults, described unique features of autoimmune hepatitis associated ALF, and are now conducting a clinical trial using intravenous (IV) N-acetylcysteine (NAC) to treat non- acetaminophen ALF.
The Specific Aims of this application are: (1) To collect, maintain, analyze and report clinical, epidemiological, and outcome data in children with ALF, including information derived from serum, tissue, and DNA specimens. Long-term outcome data on patients not enrolled in other NIH-funded pediatric consortia will be collected through the PALFSG. To conserve resources, the NIDDK repositories for tissue, DNA and serum will be utilized. These data will be used to develop predictors of prognosis, analyze trends, and provide materials to investigators. (2) To identify unrecognized mechanisms of hepatocellular injury resulting in ALF in children. Studies will assess the impact of fatty acid oxidation defects, NK cell dysfunction, and acetaminophen on the pathogenesis of ALF. Through these studies, novel treatment strategies may be developed. (3) To continue and complete the double-blind, randomized, placebo controlled trial of NAC to treat non-acetaminophen ALF. The purpose is to examine the safety and efficacy of IV NAC in children with ALF for whom there is no antidote or other specific treatment ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01DK072146-04
Application #
7486840
Study Section
Special Emphasis Panel (ZDK1-GRB-4 (M1))
Program Officer
Robuck, Patricia R
Project Start
2005-09-15
Project End
2009-08-31
Budget Start
2008-09-01
Budget End
2009-08-31
Support Year
4
Fiscal Year
2008
Total Cost
$1,056,928
Indirect Cost
Name
Children's Hosp Pittsburgh/Upmc Health Sys
Department
Type
DUNS #
044304145
City
Pittsburgh
State
PA
Country
United States
Zip Code
15224
Bryce, Cindy L; Chang, Chung Chou H; Ren, Yi et al. (2018) Using time-varying models to estimate post-transplant survival in pediatric liver transplant recipients. PLoS One 13:e0198132
Squires, James E; Rudnick, David A; Hardison, Regina M et al. (2018) Liver Transplant Listing in Pediatric Acute Liver Failure: Practices and Participant Characteristics. Hepatology 68:2338-2347
Narkewicz, Michael R; Horslen, Simon; Hardison, Regina M et al. (2018) A Learning Collaborative Approach Increases Specificity of Diagnosis of Acute Liver Failure in Pediatric Patients. Clin Gastroenterol Hepatol 16:1801-1810.e3
Sorensen, Lisa G; Neighbors, Katie; Hardison, Regina M et al. (2018) Health Related Quality of Life and Neurocognitive Outcomes in the First Year after Pediatric Acute Liver Failure. J Pediatr 196:129-138.e3
Feldman, Amy G; Sokol, Ronald J; Hardison, Regina M et al. (2017) Lactate and Lactate: Pyruvate Ratio in the Diagnosis and Outcomes of Pediatric Acute Liver Failure. J Pediatr 182:217-222.e3
Zamora, Ruben; Vodovotz, Yoram; Mi, Qi et al. (2017) Data-Driven Modeling for Precision Medicine in Pediatric Acute Liver Failure. Mol Med 22:821-829
Narkewicz, Michael R; Horslen, Simon; Belle, Steven H et al. (2017) Prevalence and Significance of Autoantibodies in Children With Acute Liver Failure. J Pediatr Gastroenterol Nutr 64:210-217
Vodovotz, Yoram (2016) Reverse Engineering the Inflammatory ""Clock"": From Computational Modeling to Rational Resetting. Drug Discov Today Dis Models 22:57-63
Li, Ruosha; Belle, Steven H; Horslen, Simon et al. (2016) Clinical Course among Cases of Acute Liver Failure of Indeterminate Diagnosis. J Pediatr 171:163-70.e1-3
Sadowsky, David; Zamora, Ruben; Barclay, Derek et al. (2016) Machine Perfusion of Porcine Livers with Oxygen-Carrying Solution Results in Reprogramming of Dynamic Inflammation Networks. Front Pharmacol 7:413

Showing the most recent 10 out of 42 publications