title: Diagnostic Accuracy of the Enhanced Liver Fibrosis (ELF®) Score Using HCV-Infected Serum Samples Cryopreserved for up to 25 Years.
abstract: OBJECTIVE
  Cryopreservation of serum samples is a standard procedure for biomedical research in tertiary centers. However, studies evaluating the long-term biological stability of direct liver fibrosis markers using cryopreserved samples are scarce.
  
  
  METHODS
  We compared the stability of hyaluronic acid (HA), tissue inhibitor of metalloproteinases (TIMP-1) and amino-terminal propeptide of type III procollagen (PIIINP) in 225 frozen serum samples of HCV-infected patients with a paired liver biopsy for up to 25 years (1990-2014). Moreover, we assessed the diagnostic accuracy (AUROC) of the Enhanced Liver Fibrosis (ELF®) score to identify significant fibrosis (F2-4) and its predictive capacity to identify clinical events during follow-up.
  
  
  RESULTS
  Seventy-six patients (39,8%) had mild fibrosis (F0-1) and 115 (60,2%) significant fibrosis (F2-4). HA, PIIINP and TIMP-1 values remained stable during the period from 1995 to 2014 while those of 1990-94 were slightly higher. We did not find significant differences in the median ELF® values during the 20-year period from 1995-2014 in patients with mild (from 8,4 to 8,7) and significant fibrosis (from 9,9 to 10,9) (p = ns between periods and fibrosis stages). The AUROCs of ELF® to identify significant fibrosis were high in all the periods (from 0,85 to 0,91). The ELF® score showed a good predictive capability to identify clinical events during follow-up.
  
  
  CONCLUSIONS
  The biological stability of direct serum markers (HA, PIIINP and TIMP-1) using HCV-infected samples cryopreserved for 20 years is good. Therefore, the diagnostic accuracy of the ELF® score to identify significant fibrosis and clinical events during follow-up is very high.
authors.affiliation: Liver Section, Gastroenterology Department, Hospital del Mar, Universitat Autònoma de Barcelona.|IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain.
authors.forename: Marc
authors.initials: M
authors.lastname: Puigvehí
authors.affiliation: Laboratori de Referència de Catalunya, Barcelona, Spain.
authors.forename: Juanjo
authors.initials: J
authors.lastname: Hernández
authors.affiliation: Liver Section, Gastroenterology Department, Hospital del Mar, Universitat Autònoma de Barcelona.|IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain.
authors.forename: Teresa
authors.initials: T
authors.lastname: Broquetas
authors.affiliation: Liver Section, Gastroenterology Department, Hospital del Mar, Universitat Autònoma de Barcelona.|IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain.
authors.forename: Susanna
authors.initials: S
authors.lastname: Coll
authors.affiliation: Liver Section, Gastroenterology Department, Hospital del Mar, Universitat Autònoma de Barcelona.|IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain.
authors.forename: Montserrat
authors.initials: M
authors.lastname: Garcia-Retortillo
authors.affiliation: Liver Section, Gastroenterology Department, Hospital del Mar, Universitat Autònoma de Barcelona.|IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain.
authors.forename: Nuria
authors.initials: N
authors.lastname: Cañete
authors.affiliation: Liver Section, Gastroenterology Department, Hospital del Mar, Universitat Autònoma de Barcelona.|IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain.
authors.forename: Maria Dolors
authors.initials: MD
authors.lastname: Giménez
authors.affiliation: Pathology Department, Hospital del Mar, Barcelona, Spain.
authors.forename: Mar
authors.initials: M
authors.lastname: Garcia
authors.affiliation: Liver Section, Gastroenterology Department, Hospital del Mar, Universitat Autònoma de Barcelona.
authors.forename: Felipe
authors.initials: F
authors.lastname: Bory
authors.affiliation: Laboratori de Referència de Catalunya, Barcelona, Spain.
authors.forename: Margarita
authors.initials: M
authors.lastname: Salvadó
authors.affiliation: Liver Section, Gastroenterology Department, Hospital del Mar, Universitat Autònoma de Barcelona.|IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain.
authors.forename: Ricard
authors.initials: R
authors.lastname: Solà
authors.affiliation: Liver Section, Gastroenterology Department, Hospital del Mar, Universitat Autònoma de Barcelona.|IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain.
authors.forename: José A
authors.initials: JA
authors.lastname: Carrión
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D015925:Cryopreservation; D005260:Female; D019698:Hepatitis C, Chronic / Q000150:complications* / Q000175:diagnosis; D006801:Humans; D006820:Hyaluronic Acid / Q000097:blood*; D008103:Liver Cirrhosis / Q000175:diagnosis*; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000097:blood*; D011347:Procollagen / Q000097:blood*; D012680:Sensitivity and Specificity; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood*; D055815:Young Adult
chemical_list: D015415:Biomarkers; D010446:Peptide Fragments; D011347:Procollagen; C560822:TIMP1 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; C041876:procollagen Type III-N-terminal peptide; D006820:Hyaluronic Acid