A Multi-Center Group to Study Acute Liver Failure in Children

NCT ID: NCT00986648

Last Updated: 2016-01-12

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 158 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2000-01-31
• Study Completion Date: 2015-12-31

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.

Conditions

Acute Liver Failure; Hepatic Encephalopathy

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

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

• Maximum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

NIH

Sponsor Role: collaborator

University of Pittsburgh

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Robert H Squires, MD

Role: PRINCIPAL_INVESTIGATOR

Children's Hospital of Pittsburgh of UPMC, University of Pittsburgh

Locations

University of California, San Francisco

San Francisco, California, United States

Children's Hospital Colorado

Aurora, Colorado, United States

Emory University, Children's Healthcare of Atlanta

Atlanta, Georgia, United States

Ann & Robert H. Lurie Children's Hospital of Chicago

Chicago, Illinois, United States

Riley Children's Hospital

Indianapolis, Indiana, United States

Johns Hopkins University

Baltimore, Maryland, United States

Harvard University, Boston Children's Hospital

Boston, Massachusetts, United States

University of Michigan

Ann Arbor, Michigan, United States

St. Louis Children's Hospital

St Louis, Missouri, United States

Mount Sinai Hospital

New York, New York, United States

Columbia-Presbyterian

New York, New York, United States

University of Cincinnati, Cincinnati Children's Hospital

Cincinnati, Ohio, United States

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Children's Hospital of Pittsburgh of UPMC

Pittsburgh, Pennsylvania, United States

Children's Medical Center of Dallas

Dallas, Texas, United States

Baylor College of Medicine

Houston, Texas, United States

University of Washington

Seattle, Washington, United States

Hospital for Sick Children

Toronto, Ontario, Canada

Birmingham Children's Hospital

Birmingham, , United Kingdom

King's College Hospital (London, UK)

London, , United Kingdom

Countries

United States; Canada; United Kingdom

References

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.

Reference Type: RESULT

PMID: 19643443 (View on PubMed)

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.

Reference Type: RESULT

PMID: 18643912 (View on PubMed)

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.

Reference Type: RESULT

PMID: 16950959 (View on PubMed)

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.

Reference Type: RESULT

PMID: 16737880 (View on PubMed)

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.

Reference Type: RESULT

PMID: 15789368 (View on PubMed)

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.

Reference Type: RESULT

PMID: 15791615 (View on PubMed)

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.

Reference Type: RESULT

PMID: 21621221 (View on PubMed)

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.

Reference Type: RESULT

PMID: 22906509 (View on PubMed)

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.

Reference Type: RESULT

PMID: 23439908 (View on PubMed)

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.

Reference Type: RESULT

PMID: 23111765 (View on PubMed)

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.

Reference Type: RESULT

PMID: 23260095 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 28088395 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 27496798 (View on PubMed)

Other Identifiers

U01DK072146

Identifier Type: NIH

Identifier Source: secondary_id

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2U01DK072146-06

Identifier Type: NIH

Identifier Source: secondary_id

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1U01DK072146-01

Identifier Type: NIH

Identifier Source: org_study_id

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