Research

A prospective assessment of the inter-laboratory variability of biochemical markers of fibrosis (FibroTest) and activity (ActiTest) in patients with chronic liver disease

Philippe Halfon¹ , Françoise Imbert-Bismut² , Djamila Messous² , Gilles Antoniotti³ , Didier Benchetrit⁴ , Philippe Cart-Lamy⁵ , Gilles Delaporte⁶ , Danièle Doutheau⁷ , Théo Klump⁸ , Michel Sala⁹ , Didier Thibaud¹⁰ , Elisabeth Trepo¹¹ , Dominique Thabut¹² , Robert P Myers¹² and Thierry Poynard¹²

¹Laboratoire Alphabio, 23 Rue de Friedland 13006 Marseille, France

²Laboratoire de Biochimie, Groupe Hospitalier Pitié-Salpêtrière, 75651 Paris, France

³Laboratoire Biomedica, 7 Rue Davat, 73100 Aix les Bains, France

⁴Laboratoire Barla, 10 Avenue Durante, 6000 Nice, France

⁵Laboratoire Clinilab, 42 Avenue de la Plaine Fleurie, 38240 Meylan, France

⁶Laboratoire Delaporte, 37 Rue de la Marne BP 25, 45501 Gien, France

⁷Laboratoire Marcel Merieux, BP 7322, 69357 Lyon Cedex 07, France

⁸Laboratoire Klump, 1 Rue Kuhn, 67000 Strasbourg, France

⁹Laboratoire Claude Levy, 78 Avenue de Verdun, 94200 Ivry-sur-Seine, France

¹⁰Laboratoire Sery, 4 Rue Gustave Cazavan, 76600 Le Havre, France

¹¹Centre de Biologie République, Centre de Biologie République, 42 Place de la République, 69002 Lyon, France

¹²Service 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

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Comparative Hepatology 2002, 1:3doi:10.1186/1476-5926-1-3

Published:	30 December 2002

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 (γ-glutamyl transpeptidase, alanine aminotransferase, α₂-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 γ-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 γ-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 γ-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 γ-glutamyl transpeptidase in multiples of the upper limit of reference values should not be employed.