Clinical trial NCT00986648: A Multi-Center Group to Study Acute Liver Failure in Children
Official title: A Multi-Center Group to Study Acute Liver Failure in Children
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Acute Liver Failure
Hepatic Encephalopathy
Keywords: acute liver failure
hepatic encephalopathy
acetaminophen toxicity
Lead sponsor: University of Pittsburgh
Sponsor class: OTHER
Collaborators: name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
First posted: 2009-09-30
Enrollment: 158
Sex: ALL
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Children between birth and age 18 years who present with acute liver failure.

Brief summary: The PALF study group began with 20 sites and now continues with 12 sites (11 in the United States and 1 in Canada) in the new funding period. The primary objective of the Pediatric Acute Liver Failure (PALF) study is to collect, maintain, analyze, and report clinical, epidemiological, and outcome data in children with ALF, including information derived from biospecimens.

Detailed description: The PALF study group will collect clinical, epidemiological and outcome data on children with ALF. This information will be used to develop methods to predict whether a child will recover from the illness without the need for a liver transplant or other life-saving procedure. We believe the methods to predict survival will vary with different patient age groups, but that diagnosis, multi-system organ failure, degree of encephalopathy and level of coagulopathy will be important regardless of patient age. Biological samples, such as blood and liver tissue, will provide opportunities to identify subgroups of patients who have unique treatment requirements and outcomes. In addition, we hope to identify unrecognized mechanisms of liver injury resulting in ALF in children. Eligible study participants will be invited to participate in neurocognitive testing. Since patients that develop acute liver failure experience varying levels of hepatic encephalopathy and cerebral edema, we suspect that there may be residual sub-clinical neurological injury that compromises long-term neurocognitive function. Detailed neurocognitive testing has never been performed in a cohort of children that survive acute liver failure and this study seeks to close that information gap by defining the spectrum of neurocognitive outcomes in this population.

Eligibility criteria: Inclusion Criteria:

* Written informed consent/assent
* Birth through 17 years of age
* Biochemical evidence of acute liver injury
* Coagulopathy not corrected by vitamin K (or other intervention intended to correct coagulopathy)

  * The presence of encephalopathy (ENC) is required if the INR is at least 1.5 and less than 2.0
  * If INR is at least 2.0, the presence of ENC is not required

Exclusion Criteria:

* Known chronic underlying liver disease
* Multi-organ system failure following heart surgery or ECMO
* Solid organ or bone marrow transplantation
* Acute trauma
* Previously enrolled in the PALF Cohort Study
* Other severe illness, condition, or other reason in the opinion of the investigator that would make the patient unsuitable for the study

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
city: Aurora
country: United States
facility: Children's Hospital Colorado
state: Colorado
city: Atlanta
country: United States
facility: Emory University, Children's Healthcare of Atlanta
state: Georgia
city: Chicago
country: United States
facility: Ann & Robert H. Lurie Children's Hospital of Chicago
state: Illinois
city: Indianapolis
country: United States
facility: Riley Children's Hospital
state: Indiana
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
city: Boston
country: United States
facility: Harvard University, Boston Children's Hospital
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: St. Louis
country: United States
facility: St. Louis Children's Hospital
state: Missouri
city: New York
country: United States
facility: Mount Sinai Hospital
state: New York
city: New York
country: United States
facility: Columbia-Presbyterian
state: New York
city: Cincinnati
country: United States
facility: University of Cincinnati, Cincinnati Children's Hospital
state: Ohio
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Children's Hospital of Pittsburgh of UPMC
state: Pennsylvania
city: Dallas
country: United States
facility: Children's Medical Center of Dallas
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Seattle
country: United States
facility: University of Washington
state: Washington
city: Toronto
country: Canada
facility: Hospital for Sick Children
state: Ontario
city: Birmingham
country: United Kingdom
facility: Birmingham Children's Hospital
city: London
country: United Kingdom
facility: King's College Hospital (London, UK)
Study officials:
affiliation: Children's Hospital of Pittsburgh of UPMC, University of Pittsburgh
name: Robert H Squires, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Narkewicz MR, Dell Olio D, Karpen SJ, Murray KF, Schwarz K, Yazigi N, Zhang S, Belle SH, Squires RH; Pediatric Acute Liver Failure Study Group. Pattern of diagnostic evaluation for the causes of pediatric acute liver failure: an opportunity for quality improvement. J Pediatr. 2009 Dec;155(6):801-806.e1. doi: 10.1016/j.jpeds.2009.06.005. Epub 2009 Jul 29.
citation: Rudnick DA, Dietzen DJ, Turmelle YP, Shepherd R, Zhang S, Belle SH, Squires R; Pediatric Acute Liver Failure Study Group. Serum alpha-NH-butyric acid may predict spontaneous survival in pediatric acute liver failure. Pediatr Transplant. 2009 Mar;13(2):223-30. doi: 10.1111/j.1399-3046.2008.00998.x. Epub 2008 Jul 17.
citation: James LP, Alonso EM, Hynan LS, Hinson JA, Davern TJ, Lee WM, Squires RH; Pediatric Acute Liver Failure Study Group. Detection of acetaminophen protein adducts in children with acute liver failure of indeterminate cause. Pediatrics. 2006 Sep;118(3):e676-81. doi: 10.1542/peds.2006-0069.
citation: Squires RH Jr, Shneider BL, Bucuvalas J, Alonso E, Sokol RJ, Narkewicz MR, Dhawan A, Rosenthal P, Rodriguez-Baez N, Murray KF, Horslen S, Martin MG, Lopez MJ, Soriano H, McGuire BM, Jonas MM, Yazigi N, Shepherd RW, Schwarz K, Lobritto S, Thomas DW, Lavine JE, Karpen S, Ng V, Kelly D, Simonds N, Hynan LS. Acute liver failure in children: the first 348 patients in the pediatric acute liver failure study group. J Pediatr. 2006 May;148(5):652-658. doi: 10.1016/j.jpeds.2005.12.051.
citation: Alonso EM. Acute liver failure in children: the role of defects in fatty acid oxidation. Hepatology. 2005 Apr;41(4):696-9. doi: 10.1002/hep.20680. No abstract available.
citation: Shneider BL, Rinaldo P, Emre S, Bucuvalas J, Squires R, Narkewicz M, Gondolesi G, Magid M, Morotti R, Hynan LS. Abnormal concentrations of esterified carnitine in bile: a feature of pediatric acute liver failure with poor prognosis. Hepatology. 2005 Apr;41(4):717-21. doi: 10.1002/hep.20631.
citation: Sundaram SS, Alonso EM, Narkewicz MR, Zhang S, Squires RH; Pediatric Acute Liver Failure Study Group. Characterization and outcomes of young infants with acute liver failure. J Pediatr. 2011 Nov;159(5):813-818.e1. doi: 10.1016/j.jpeds.2011.04.016. Epub 2011 May 31.
citation: Sundaram V, Shneider BL, Dhawan A, Ng VL, Im K, Belle S, Squires RH. King's College Hospital Criteria for non-acetaminophen induced acute liver failure in an international cohort of children. J Pediatr. 2013 Feb;162(2):319-23.e1. doi: 10.1016/j.jpeds.2012.07.002. Epub 2012 Aug 18.
citation: Leonis MA, Alonso EM, Im K, Belle SH, Squires RH; Pediatric Acute Liver Failure Study Group. Chronic acetaminophen exposure in pediatric acute liver failure. Pediatrics. 2013 Mar;131(3):e740-6. doi: 10.1542/peds.2011-3035. Epub 2013 Feb 25.
citation: Bucuvalas J, Filipovich L, Yazigi N, Narkewicz MR, Ng V, Belle SH, Zhang S, Squires RH. Immunophenotype predicts outcome in pediatric acute liver failure. J Pediatr Gastroenterol Nutr. 2013 Mar;56(3):311-5. doi: 10.1097/MPG.0b013e31827a78b2.
citation: Lu BR, Zhang S, Narkewicz MR, Belle SH, Squires RH, Sokol RJ; Pediatric Acute Liver Failure Study Group. Evaluation of the liver injury unit scoring system to predict survival in a multinational study of pediatric acute liver failure. J Pediatr. 2013 May;162(5):1010-6.e1-4. doi: 10.1016/j.jpeds.2012.11.021. Epub 2012 Dec 20.
citation: Feldman AG, Sokol RJ, Hardison RM, Alonso EM, Squires RH, Narkewicz MR; Pediatric Acute Liver Failure Study Group. Lactate and Lactate: Pyruvate Ratio in the Diagnosis and Outcomes of Pediatric Acute Liver Failure. J Pediatr. 2017 Mar;182:217-222.e3. doi: 10.1016/j.jpeds.2016.12.031. Epub 2017 Jan 12.
citation: Narkewicz MR, Horslen S, Belle SH, Rudnick DA, Ng VL, Rosenthal P, Romero R, Loomes KM, Zhang S, Hardison RM, Squires RH; Pediatric Acute Liver Failure Study Group. Prevalence and Significance of Autoantibodies in Children With Acute Liver Failure. J Pediatr Gastroenterol Nutr. 2017 Feb;64(2):210-217. doi: 10.1097/MPG.0000000000001363.