Document Detail


A longitudinal study to identify laboratory predictors of liver disease outcome in Alagille syndrome.
MedLine Citation:
PMID:  20421762     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVES: Liver disease in Alagille syndrome (AGS) is highly variable, ranging from biochemical abnormalities only to end-stage disease. It is not possible to predict whether a child with cholestasis will have improvement or progression of liver disease. This poses a challenge to the clinician in terms of timing therapies. The study aim was to identify laboratory markers present in children younger than 5 years that could predict the ultimate outcome of liver disease in AGS.
METHODS: A retrospective review of laboratory data from 33 subjects with AGS was performed. Patients older than 10 years of age were stratified into mild (22) and severe (11) hepatic outcome groups. Nonparametric analysis was performed on longitudinal data from birth to 5 years to determine association with hepatic outcome. JAGGED1 mutational analysis was performed on available samples.
RESULTS: The following variables were statistically different between severe and mild outcome groups: total bilirubin (TB, P = 0.0001), conjugated bilirubin (CB, P = 0.0066), and cholesterol (P = 0.0022). Further analysis revealed cutoff values that differentiated between severe and mild outcomes; TB 6.5 mg/dL (111 micromol/L), CB 4.5 mg/dL (77 micromol/L), and cholesterol 520 mg/dL (13.5 mmol/L). Genetic analysis of JAGGED1 mutations did not reveal genotype-phenotype correlation.
CONCLUSIONS: TB >6.5 mg/dL, CB >4.5 mg/dL, and cholesterol >520 mg/dL in children younger than 5 years of age are likely to be associated with severe liver disease in later life. These data represent cutoff values below which a child is likely to have a benign outcome and above which more aggressive therapy may be warranted, and can thus be used to guide management.
Authors:
Binita M Kamath; Pedro S Munoz; Natalie Bab; Alastair Baker; Zhongxue Chen; Nancy B Spinner; David A Piccoli
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Journal of pediatric gastroenterology and nutrition     Volume:  50     ISSN:  1536-4801     ISO Abbreviation:  J. Pediatr. Gastroenterol. Nutr.     Publication Date:  2010 May 
Date Detail:
Created Date:  2010-04-27     Completed Date:  2011-02-15     Revised Date:  2012-05-15    
Medline Journal Info:
Nlm Unique ID:  8211545     Medline TA:  J Pediatr Gastroenterol Nutr     Country:  United States    
Other Details:
Languages:  eng     Pagination:  526-30     Citation Subset:  IM    
Affiliation:
Division of Gastroenterology, Children's Hospital of Philadelphia, USA. binita.kamath@sickkids.ca
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MeSH Terms
Descriptor/Qualifier:
Alagille Syndrome / blood*,  genetics
Bilirubin / blood*
Biological Markers / blood
Calcium-Binding Proteins / genetics
Child
Child, Preschool
Cholesterol / blood*
Disease Progression
Genotype
Humans
Infant
Intercellular Signaling Peptides and Proteins / genetics
Liver Diseases / blood,  etiology*,  genetics
Longitudinal Studies
Membrane Proteins / genetics
Mutation
Phenotype
Prognosis
Reference Values
Retrospective Studies
Severity of Illness Index
Grant Support
ID/Acronym/Agency:
R01 DK053104-09S1/DK/NIDDK NIH HHS; R01 DK081702/DK/NIDDK NIH HHS; R01 DK081702-03/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Biological Markers; 0/Calcium-Binding Proteins; 0/Intercellular Signaling Peptides and Proteins; 0/Membrane Proteins; 134324-36-0/Serrate proteins; 57-88-5/Cholesterol; 635-65-4/Bilirubin
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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