title: The role of serum biomarkers in predicting fibrosis progression in pediatric and adult hepatitis C virus chronic infection.
abstract: OBJECTIVE
  Liver biopsy represents the gold standard for damage evaluation, but noninvasive serum markers that mirror liver fibrosis progression are actual goals both in adults and especially in children. The aim was to determine specific serum markers that correlate with liver fibrosis progression during chronic HCV infection.
  
  
  METHODS
  Liver biopsies and concomitant serum samples from 22 pediatric and 22 adult HCV patients were analyzed. Histological parameters were evaluated. On serum TGF-ß1, tissue inhibitor of matrix metalloprotein inhibitor-1 (TIMP-1), hyaluronic acid (HA) and aminoterminal peptide of procollagen type III (PIIINP) were tested.
  
  
  RESULTS
  Significant fibrosis (F≥2) and advanced fibrosis (F≥3) represented 64% and 20%, respectively in children; while 54% F≥2 and 23% F≥3 in adults. Hyaluronic acid (p = 0.011) and PIIINP (p = 0.016) were related to worse fibrosis stages only in adults, along with TIMP-1 (p = 0.039) just in children; but TGF-ß1 was associated with mild fibrosis (p = 0.022) in adults. The AUROC of TIMP-1 in children to discriminate advanced fibrosis was 0.800 (95%IC 0.598-0.932). In adults, the best AUROCs were that of HA, PIIINP and TGF-ß1 [0.929 (IC95% 0.736-0.994), 0.894 (IC95% 0.689-0.984) and 0.835 (IC95% 0.617-0.957)], respectively. In children, according to the cut off (165.7 ng/mL) value for TIMP-1, biopsies could have been avoided in 72% (18/25). Considering the cut off for HA (109.7 ng/mL), PIIINP (9.1 µg/L), and TGF-ß1 (10,848.3 pg/mL), biopsies could have been avoided in 87% (19/22) of adult patients by using HA and 73% (16/22) using PIIINP or TGF-ß1.
  
  
  CONCLUSIONS
  In adults given the diagnostic accuracy of HA, PIIINP, TGF-ß1, their combination may provide a potential useful tool to assess liver fibrosis. This first pediatric study suggests that TIMP-1 is clinically useful for predicting liver fibrosis in HCV patients.
authors.affiliation: Laboratory of Molecular Biology, Pathology Division, Ricardo Gutiérrez Children's Hospital, Buenos Aires, Argentina. valvapamela@yahoo.com
authors.forename: Pamela
authors.initials: P
authors.lastname: Valva
authors.forename: Paola
authors.initials: P
authors.lastname: Casciato
authors.forename: Juan M
authors.initials: JM
authors.lastname: Diaz Carrasco
authors.forename: Adrian
authors.initials: A
authors.lastname: Gadano
authors.forename: Omar
authors.initials: O
authors.lastname: Galdame
authors.forename: María Cristina
authors.initials: MC
authors.lastname: Galoppo
authors.forename: Eduardo
authors.initials: E
authors.lastname: Mullen
authors.forename: Elena
authors.initials: E
authors.lastname: De Matteo
authors.forename: María Victoria
authors.initials: MV
authors.lastname: Preciado
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood*; D001706:Biopsy; D002648:Child; D002675:Child, Preschool; D018450:Disease Progression; D005260:Female; D019698:Hepatitis C, Chronic / Q000097:blood* / Q000473:pathology / Q000821:virology; D006801:Humans; D006820:Hyaluronic Acid / Q000097:blood; D007118:Immunoassay / Q000379:methods; D007223:Infant; D008099:Liver / Q000473:pathology / Q000821:virology; D008103:Liver Cirrhosis / Q000097:blood* / Q000175:diagnosis / Q000821:virology; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000097:blood; D011237:Predictive Value of Tests; D011347:Procollagen / Q000097:blood; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood; D053773:Transforming Growth Factor beta1 / Q000097:blood
chemical_list: D015415:Biomarkers; D010446:Peptide Fragments; D011347:Procollagen; D019715:Tissue Inhibitor of Metalloproteinase-1; D053773:Transforming Growth Factor beta1; C041876:procollagen Type III-N-terminal peptide; D006820:Hyaluronic Acid