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

Identifieur interne : 000129 ( Pmc/Curation ); précédent : 000128; suivant : 000130

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

Auteurs : Philippe Halfon [France] ; Françoise Imbert-Bismut [France] ; Djamila Messous [France] ; Gilles Antoniotti [France] ; Didier Benchetrit [France] ; Philippe Cart-Lamy [France] ; Gilles Delaporte [France] ; Danièle Doutheau [France] ; Théo Klump [France] ; Michel Sala [France] ; Didier Thibaud [France] ; Elisabeth Trepo [France] ; Dominique Thabut [France] ; Robert P. Myers [France] ; Thierry Poynard [France]

Source :

RBID : PMC:149429

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.


Url:
DOI: 10.1186/1476-5926-1-3
PubMed: 12537583
PubMed Central: 149429

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PMC:149429

Le document en format XML

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<name sortKey="Doutheau, Daniele" sort="Doutheau, Daniele" uniqKey="Doutheau D" first="Danièle" last="Doutheau">Danièle Doutheau</name>
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<nlm:aff id="I7">Laboratoire Marcel Merieux, BP 7322, 69357 Lyon Cedex 07, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Laboratoire Marcel Merieux, BP 7322, 69357 Lyon Cedex 07</wicri:regionArea>
</affiliation>
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<name sortKey="Klump, Theo" sort="Klump, Theo" uniqKey="Klump T" first="Théo" last="Klump">Théo Klump</name>
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<country xml:lang="fr">France</country>
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<name sortKey="Sala, Michel" sort="Sala, Michel" uniqKey="Sala M" first="Michel" last="Sala">Michel Sala</name>
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<nlm:aff id="I9">Laboratoire Claude Levy, 78 Avenue de Verdun, 94200 Ivry-sur-Seine, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Laboratoire Claude Levy, 78 Avenue de Verdun, 94200 Ivry-sur-Seine</wicri:regionArea>
</affiliation>
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<name sortKey="Thibaud, Didier" sort="Thibaud, Didier" uniqKey="Thibaud D" first="Didier" last="Thibaud">Didier Thibaud</name>
<affiliation wicri:level="1">
<nlm:aff id="I10">Laboratoire Sery, 4 Rue Gustave Cazavan, 76600 Le Havre, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Laboratoire Sery, 4 Rue Gustave Cazavan, 76600 Le Havre</wicri:regionArea>
</affiliation>
</author>
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<name sortKey="Trepo, Elisabeth" sort="Trepo, Elisabeth" uniqKey="Trepo E" first="Elisabeth" last="Trepo">Elisabeth Trepo</name>
<affiliation wicri:level="1">
<nlm:aff id="I11">Centre de Biologie République, Centre de Biologie République, 42 Place de la République, 69002 Lyon, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Centre de Biologie République, Centre de Biologie République, 42 Place de la République, 69002 Lyon</wicri:regionArea>
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<name sortKey="Thabut, Dominique" sort="Thabut, Dominique" uniqKey="Thabut D" first="Dominique" last="Thabut">Dominique Thabut</name>
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<nlm:aff id="I12">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</nlm:aff>
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</affiliation>
</author>
<author>
<name sortKey="Myers, Robert P" sort="Myers, Robert P" uniqKey="Myers R" first="Robert P" last="Myers">Robert P. Myers</name>
<affiliation wicri:level="1">
<nlm:aff id="I12">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</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>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</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Poynard, Thierry" sort="Poynard, Thierry" uniqKey="Poynard T" first="Thierry" last="Poynard">Thierry Poynard</name>
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<country xml:lang="fr">France</country>
<wicri:regionArea>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</wicri:regionArea>
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<title>Background</title>
<p>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, α
<sub>2</sub>
-macroglobulin, haptoglobin, apolipoprotein A1, and total bilirubin) and to identify factors associated with this variability.</p>
</sec>
<sec>
<title>Results</title>
<p>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.</p>
</sec>
<sec>
<title>Conclusions</title>
<p>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.</p>
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<journal-id journal-id-type="nlm-ta">Comp Hepatol</journal-id>
<journal-title>Comparative Hepatology</journal-title>
<issn pub-type="epub">1476-5926</issn>
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<article-id pub-id-type="pmid">12537583</article-id>
<article-id pub-id-type="pmc">149429</article-id>
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<article-id pub-id-type="doi">10.1186/1476-5926-1-3</article-id>
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<title-group>
<article-title>A prospective assessment of the inter-laboratory variability of biochemical markers of fibrosis (FibroTest) and activity (ActiTest) in patients with chronic liver disease</article-title>
</title-group>
<contrib-group>
<contrib id="A1" contrib-type="author">
<name>
<surname>Halfon</surname>
<given-names>Philippe</given-names>
</name>
<xref ref-type="aff" rid="I1">1</xref>
<email>philippe.halfon@alphabio.fr</email>
</contrib>
<contrib id="A2" contrib-type="author">
<name>
<surname>Imbert-Bismut</surname>
<given-names>Françoise</given-names>
</name>
<xref ref-type="aff" rid="I2">2</xref>
<email>francoise.bismut@psl.ap-hop-paris.fr</email>
</contrib>
<contrib id="A3" contrib-type="author">
<name>
<surname>Messous</surname>
<given-names>Djamila</given-names>
</name>
<xref ref-type="aff" rid="I2">2</xref>
<email>francoise.bismut@psl.ap-hop-paris.fr</email>
</contrib>
<contrib id="A4" contrib-type="author">
<name>
<surname>Antoniotti</surname>
<given-names>Gilles</given-names>
</name>
<xref ref-type="aff" rid="I3">3</xref>
<email>lamanton@bio-medica.com</email>
</contrib>
<contrib id="A5" contrib-type="author">
<name>
<surname>Benchetrit</surname>
<given-names>Didier</given-names>
</name>
<xref ref-type="aff" rid="I4">4</xref>
<email>d.benche@azurbio.org</email>
</contrib>
<contrib id="A6" contrib-type="author">
<name>
<surname>Cart-Lamy</surname>
<given-names>Philippe</given-names>
</name>
<xref ref-type="aff" rid="I5">5</xref>
<email>cartlamy@aol.com</email>
</contrib>
<contrib id="A7" contrib-type="author">
<name>
<surname>Delaporte</surname>
<given-names>Gilles</given-names>
</name>
<xref ref-type="aff" rid="I6">6</xref>
<email>labdelap45@aol.com</email>
</contrib>
<contrib id="A8" contrib-type="author">
<name>
<surname>Doutheau</surname>
<given-names>Danièle</given-names>
</name>
<xref ref-type="aff" rid="I7">7</xref>
<email>tpoynard@teaser.fr</email>
</contrib>
<contrib id="A9" contrib-type="author">
<name>
<surname>Klump</surname>
<given-names>Théo</given-names>
</name>
<xref ref-type="aff" rid="I8">8</xref>
<email>klumpp@noos.fr</email>
</contrib>
<contrib id="A10" contrib-type="author">
<name>
<surname>Sala</surname>
<given-names>Michel</given-names>
</name>
<xref ref-type="aff" rid="I9">9</xref>
<email>m.sala@lablcl.com</email>
</contrib>
<contrib id="A11" contrib-type="author">
<name>
<surname>Thibaud</surname>
<given-names>Didier</given-names>
</name>
<xref ref-type="aff" rid="I10">10</xref>
<email>d.thibaud@bioceane.fr</email>
</contrib>
<contrib id="A12" contrib-type="author">
<name>
<surname>Trepo</surname>
<given-names>Elisabeth</given-names>
</name>
<xref ref-type="aff" rid="I11">11</xref>
<email>e.trepo@labo-republique.com</email>
</contrib>
<contrib id="A13" contrib-type="author">
<name>
<surname>Thabut</surname>
<given-names>Dominique</given-names>
</name>
<xref ref-type="aff" rid="I12">12</xref>
<email>dthabut@libertysurf.fr</email>
</contrib>
<contrib id="A14" contrib-type="author">
<name>
<surname>Myers</surname>
<given-names>Robert P</given-names>
</name>
<xref ref-type="aff" rid="I12">12</xref>
<email>drrobpmyers@hotmail.com</email>
</contrib>
<contrib id="A15" corresp="yes" contrib-type="author">
<name>
<surname>Poynard</surname>
<given-names>Thierry</given-names>
</name>
<xref ref-type="aff" rid="I12">12</xref>
<email>tpoynard@teaser.fr</email>
</contrib>
</contrib-group>
<aff id="I1">
<label>1</label>
Laboratoire Alphabio, 23 Rue de Friedland 13006 Marseille, France</aff>
<aff id="I2">
<label>2</label>
Laboratoire de Biochimie, Groupe Hospitalier Pitié-Salpêtrière, 75651 Paris, France</aff>
<aff id="I3">
<label>3</label>
Laboratoire Biomedica, 7 Rue Davat, 73100 Aix les Bains, France</aff>
<aff id="I4">
<label>4</label>
Laboratoire Barla, 10 Avenue Durante, 6000 Nice, France</aff>
<aff id="I5">
<label>5</label>
Laboratoire Clinilab, 42 Avenue de la Plaine Fleurie, 38240 Meylan, France</aff>
<aff id="I6">
<label>6</label>
Laboratoire Delaporte, 37 Rue de la Marne BP 25, 45501 Gien, France</aff>
<aff id="I7">
<label>7</label>
Laboratoire Marcel Merieux, BP 7322, 69357 Lyon Cedex 07, France</aff>
<aff id="I8">
<label>8</label>
Laboratoire Klump, 1 Rue Kuhn, 67000 Strasbourg, France</aff>
<aff id="I9">
<label>9</label>
Laboratoire Claude Levy, 78 Avenue de Verdun, 94200 Ivry-sur-Seine, France</aff>
<aff id="I10">
<label>10</label>
Laboratoire Sery, 4 Rue Gustave Cazavan, 76600 Le Havre, France</aff>
<aff id="I11">
<label>11</label>
Centre de Biologie République, Centre de Biologie République, 42 Place de la République, 69002 Lyon, France</aff>
<aff id="I12">
<label>12</label>
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</aff>
<pub-date pub-type="collection">
<year>2002</year>
</pub-date>
<pub-date pub-type="epub">
<day>30</day>
<month>12</month>
<year>2002</year>
</pub-date>
<volume>1</volume>
<fpage>3</fpage>
<lpage>3</lpage>
<ext-link ext-link-type="uri" xlink:href="http://www.comparative-hepatology.com/content/1/1/3"></ext-link>
<history>
<date date-type="received">
<day>24</day>
<month>9</month>
<year>2002</year>
</date>
<date date-type="accepted">
<day>30</day>
<month>12</month>
<year>2002</year>
</date>
</history>
<permissions>
<copyright-statement>Copyright © 2002 Halfon et al; licensee BioMed Central Ltd. This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original URL.</copyright-statement>
<copyright-year>2002</copyright-year>
<copyright-holder>Halfon et al; licensee BioMed Central Ltd. This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original URL.</copyright-holder>
</permissions>
<abstract>
<sec>
<title>Background</title>
<p>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, α
<sub>2</sub>
-macroglobulin, haptoglobin, apolipoprotein A1, and total bilirubin) and to identify factors associated with this variability.</p>
</sec>
<sec>
<title>Results</title>
<p>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.</p>
</sec>
<sec>
<title>Conclusions</title>
<p>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.</p>
</sec>
</abstract>
</article-meta>
</front>
</pmc>
</record>

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