title: Hyaluronic acid predicts hepatic fibrosis in children with hepatic disease.
abstract: BACKGROUND
  Hyaluronic acid (HA) is removed by the liver via sinusoidal cell adhesion molecules. This is impeded in fibrosis, leading to a rise in serum HA. As a noninvasive marker of fibrosis, HA may obviate the need for liver biopsy.
  
  
  OBJECTIVE
  To evaluate HA as a marker of hepatic fibrosis, in unselected children undergoing liver biopsy.
  
  
  METHODS
  Ninety-three unselected consecutive children (median age, 7.5 years; range, 0.07-19 years) undergoing a liver biopsy between April 2003 and March 2004 were prospectively recruited. Liver biopsy and fasting HA levels were taken simultaneously. The Ishak score was used to stage fibrosis. Scores of 3 or greater were regarded as significant fibrosis. Hyaluronic acid levels were measured using an enzyme-linked binding protein assay (2002 Corgenix, Inc) (adult reference range, 0-75 ng/mL; pediatric reference range, 0-30 ng/mL).
  
  
  RESULTS
  Twenty-three (25%) of 93 biopsies had significant fibrosis, and HA levels in this group were significantly higher than those with mild fibrosis (Ishak score, <3), (median level, 72 ng/mL vs 30 ng/mL; Mann-Whitney U test; P < 0.005). Hyaluronic acid level of 50 ng/mL had a positive predictive value 40% and negative predictive value 86% for significant fibrosis. An HA level 200 ng/mL has a sensitivity of 26% and specificity of 90%.
  
  
  CONCLUSIONS
  Hyaluronic Acid is a valid noninvasive predictor of hepatic fibrosis in unselected children with liver disease. An HA level of 200 ng/mL strongly suggests significant fibrosis. Hyaluronic acid level of less than 50 ng/mL accurately identifies those who do not have significant fibrosis.
authors.affiliation: Birmingham Children's Hospital, UK. janehartley@doctors.org.uk
authors.forename: Jane L
authors.initials: JL
authors.lastname: Hartley
authors.forename: Rachel M
authors.initials: RM
authors.lastname: Brown
authors.forename: Aniela
authors.initials: A
authors.lastname: Tybulewicz
authors.forename: Peter
authors.initials: P
authors.lastname: Hayes
authors.forename: David C
authors.initials: DC
authors.lastname: Wilson
authors.forename: Peter
authors.initials: P
authors.lastname: Gillett
authors.forename: Patrick
authors.initials: P
authors.lastname: McKiernan
mesh_terms: D000293:Adolescent; D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D019540:Area Under Curve; D001219:Aspartate Aminotransferases / Q000097:blood; D015415:Biomarkers / Q000097:blood; D001706:Biopsy; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D006820:Hyaluronic Acid / Q000097:blood*; D007223:Infant; D008099:Liver / Q000473:pathology*; D008103:Liver Cirrhosis / Q000097:blood* / Q000175:diagnosis*; D008111:Liver Function Tests; D008297:Male; D011237:Predictive Value of Tests; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index
chemical_list: D015415:Biomarkers; D006820:Hyaluronic Acid; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase