title: Concordance in a world without a gold standard: a new non-invasive methodology for improving accuracy of fibrosis markers.
abstract: BACKGROUND
  Assessing liver fibrosis is traditionally performed by biopsy, an imperfect gold standard. Non-invasive techniques, liver stiffness measurements (LSM) and biomarkers [FibroTest(R) (FT)], are widely used in countries where they are available. The aim was to identify factors associated with LSM accuracy using FT as a non-invasive endpoint and vice versa.
  
  
  METHODS
  The proof of concept was taken using the manufacturers recommendations for excluding patients at high risk of false negative/positive. The hypothesis was that the concordance between LSM and FT, would be improved by excluding high-risk patients. Thereafter, the impact of potential variability factors was assessed by the same methods. Liver biopsy and independent endpoints were used to validate the results.
  
  
  RESULTS
  Applying manufacturers' recommendations in 2,004 patients increased the strength of concordance between LSM and FT (P<0.00001). Among the 1,338 patients satisfying recommendations, the methodology identified a significant LSM operator effect (P = 0.001) and the following variability factors (all P<0.01), related to LSM: male gender, older age, and NAFLD as a cause of liver disease. Biopsy confirmed in 391 patients these results.
  
  
  CONCLUSIONS
  This study has validated the concept of using the strength of concordance between non-invasive estimates of liver fibrosis for the identification of factors associated with variability and precautions of use.
authors.affiliation: APHP Groupe Hospitalier Pitié-Salpêtrière, Université Paris VI, CNRS UMR, Paris, France. tpoynard@teaser.fr
authors.forename: Thierry
authors.initials: T
authors.lastname: Poynard
authors.forename: Patrick
authors.initials: P
authors.lastname: Ingiliz
authors.forename: Laure
authors.initials: L
authors.lastname: Elkrief
authors.forename: Mona
authors.initials: M
authors.lastname: Munteanu
authors.forename: Pascal
authors.initials: P
authors.lastname: Lebray
authors.forename: Rachel
authors.initials: R
authors.lastname: Morra
authors.forename: Djamila
authors.initials: D
authors.lastname: Messous
authors.forename: Francoise Imbert
authors.initials: FI
authors.lastname: Bismut
authors.forename: Dominique
authors.initials: D
authors.lastname: Roulot
authors.forename: Yves
authors.initials: Y
authors.lastname: Benhamou
authors.forename: Dominique
authors.initials: D
authors.lastname: Thabut
authors.forename: Vlad
authors.initials: V
authors.lastname: Ratziu
mesh_terms: D015415:Biomarkers / Q000032:analysis; D001706:Biopsy; D005234:Fatty Liver / Q000473:pathology; D005260:Female; D006801:Humans; D008099:Liver / Q000473:pathology; D008103:Liver Cirrhosis / Q000175:diagnosis* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D012015:Reference Standards; D015203:Reproducibility of Results
chemical_list: D015415:Biomarkers