title: A prospective assessment of the inter-laboratory variability of biochemical markers of fibrosis (FibroTest) and activity (ActiTest) in patients with chronic liver disease.
abstract: BACKGROUND: Biochemical markers for liver fibrosis (FibroTest) and necroinflammatory features (ActiTest) are an alternative to liver biopsy in patients with chronic hepatitis C. Our aim was to assess the inter-laboratory variability of these tests, and their 6 components (gamma-glutamyl transpeptidase, alanine aminotransferase, alpha2-macroglobulin, haptoglobin, apolipoprotein A1, and total bilirubin) and to identify factors associated with this variability. RESULTS: Serum of 24 patients with chronic hepatitis C or severe alcoholic liver disease were prospectively recorded and analyzed in one reference center and in 8 additional laboratories. When gamma-glutamyl transpeptidase and alanine aminotransferase were expressed in international units, there was no significant difference between laboratories in the results of FibroTest or ActiTest; kappa statistics were greater than 0.50 with only 0.8% of cases (3/384) with a discordance of more than one stage. The main factor significantly associated with variability was the expression of gamma-glutamyl transpeptidase and alanine aminotransferase, as multiples of upper limit of reference values. The use of standardized method with pyridoxal phosphate reduced the variability of alanine aminotransferase expression, and standardized original Szasz method reduced the variability of gamma-glutamyl transpeptidase expression. CONCLUSIONS: The variability of FibroTest and ActiTest was acceptable without clinical consequences for the prediction of the stage of liver fibrosis and grade of activity. Standardized methods and assay calibration should be used and expression of alanine aminotransferase and gamma-glutamyl transpeptidase in multiples of the upper limit of reference values should not be employed.
authors.affiliation: Service d'Hépato-Gastroentérologie, Groupe Hospitalier Pitié-Salpêtrière, AP-HP, Université Paris 6 et UPRESA 8067 CNRS Paris, 47 Boulevard de l'Hôpital, 75651 Paris Cedex 13, France. tpoynard@teaser.fr
authors.forename: Philippe
authors.initials: P
authors.lastname: Halfon
authors.forename: Françoise
authors.initials: F
authors.lastname: Imbert-Bismut
authors.forename: Djamila
authors.initials: D
authors.lastname: Messous
authors.forename: Gilles
authors.initials: G
authors.lastname: Antoniotti
authors.forename: Didier
authors.initials: D
authors.lastname: Benchetrit
authors.forename: Philippe
authors.initials: P
authors.lastname: Cart-Lamy
authors.forename: Gilles
authors.initials: G
authors.lastname: Delaporte
authors.forename: Danièle
authors.initials: D
authors.lastname: Doutheau
authors.forename: Théo
authors.initials: T
authors.lastname: Klump
authors.forename: Michel
authors.initials: M
authors.lastname: Sala
authors.forename: Didier
authors.initials: D
authors.lastname: Thibaud
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Trepo
authors.forename: Dominique
authors.initials: D
authors.lastname: Thabut
authors.forename: Robert P
authors.initials: RP
authors.lastname: Myers
authors.forename: Thierry
authors.initials: T
authors.lastname: Poynard