title: Serum biomarkers and transient elastography as predictors of advanced liver fibrosis in a United States cohort: the Boston children's hospital experience.
abstract: OBJECTIVE
  To evaluate and compare the ability of serum hyaluronic acid (HA) and human cartilage glycoprotein-39 (YKL-40) values, as well as transient elastography (TE) findings, to predict advanced hepatic fibrosis in a cohort from a single pediatric center.
  
  
  METHODS
  Subjects who underwent liver biopsy analysis within 12 months before enrollment were eligible for this prospective study. HA and YKL-40 measurements were obtained within 1 month of TE. A METAVIR score of F3 or F4 was considered to indicate advanced fibrosis.
  
  
  RESULTS
  A total of 128 patients (51% males) aged 1.4 months to 27.6 years (22% aged <2 years) were enrolled. Thirty-one subjects had data on only HA and YKL-40 measurements, and 97 subjects had data on both blood tests and TE. For the prediction of advanced fibrosis, the area under the receiver operating characteristic curve (AUC) values were 0.83 for TE, 0.72 for HA, and 0.52 for YKL-40. The AUC of 0.83 for TE was statistically significantly greater than the AUCs for HA (P = .03) and YKL-40 (P < .0001). Optimal cutpoints for predicting F3-F4 fibrosis were 8.6 kPa for TE (P < .0001), 43 ng/mL for HA (P < .0001), and 26.2 ng/mL for YKL-40 (P = .85). The combination of TE and HA was not better than TE alone for predicting advanced fibrosis (P = .15).
  
  
  CONCLUSIONS
  In this study, which evaluated TE, HA, and YKL-40 to predict liver fibrosis in children in the US, YKL-40 had no predictive value and TE was superior to HA, but the addition of HA did not improve the performance of TE. Our data suggest that TE and HA may be useful noninvasive tools for assessing liver fibrosis in children.
authors.affiliation: Division of Gastroenterology, Hepatology and Nutrition, Boston Children's Hospital, Boston, MA. Electronic address: Christine.Lee@childrens.harvard.edu.
authors.forename: Christine K
authors.initials: CK
authors.lastname: Lee
authors.forename: Antonio R
authors.initials: AR
authors.lastname: Perez-Atayde
authors.forename: Paul D
authors.initials: PD
authors.lastname: Mitchell
authors.forename: Roshan
authors.initials: R
authors.lastname: Raza
authors.forename: Nezam H
authors.initials: NH
authors.lastname: Afdhal
authors.forename: Maureen M
authors.initials: MM
authors.lastname: Jonas
mesh_terms: D054392:Adipokines / Q000097:blood; D000293:Adolescent; D000328:Adult; D019540:Area Under Curve; D015415:Biomarkers / Q000097:blood*; D001706:Biopsy; D001900:Boston; D002648:Child; D002675:Child, Preschool; D000071451:Chitinase-3-Like Protein 1; D015331:Cohort Studies; D054459:Elasticity Imaging Techniques / Q000379:methods*; D005260:Female; D005355:Fibrosis; D006776:Hospitals, Pediatric; D006801:Humans; D006820:Hyaluronic Acid / Q000097:blood; D007223:Infant; D037102:Lectins / Q000097:blood; D008103:Liver Cirrhosis / Q000097:blood* / Q000175:diagnosis / Q000473:pathology; D008297:Male; D011237:Predictive Value of Tests; D011446:Prospective Studies; D055815:Young Adult
chemical_list: D054392:Adipokines; D015415:Biomarkers; C084533:CHI3L1 protein, human; D000071451:Chitinase-3-Like Protein 1; D037102:Lectins; D006820:Hyaluronic Acid
keywords: ALT; APRI; AST; AUC; Alanine aminotransferase; Area under the receiver operating characteristic curve; Aspartate aminotransferase; Aspartate aminotransferase:platelet ratio index; GGTP; Gamma-glutamyl transpeptidase; HA; Human cartilage glycoprotein-39; Hyaluronic acid; NAFLD; NPV; Negative predictive value; Nonalcoholic fatty liver disease; PPV; Positive predictive value; ROC; Receiver operating characteristic; TE; Transient elastography; YKL-40