Age as a Confounding Factor for the Accurate Non-Invasive Diagnosis of Advanced NAFLD Fibrosis
Identifieur interne : 000B42 ( Pmc/Checkpoint ); précédent : 000B41; suivant : 000B43Age as a Confounding Factor for the Accurate Non-Invasive Diagnosis of Advanced NAFLD Fibrosis
Auteurs : Stuart Mcpherson [Royaume-Uni] ; Tim Hardy [Royaume-Uni] ; Jean-Francois Dufour [Suisse] ; Salvatore Petta [Italie] ; Manuel Romero-Gomez [Espagne] ; Mike Allison [Royaume-Uni] ; Claudia P. Oliveira [Brésil] ; Sven Francque [Belgique] ; Luc Van Gaal [Belgique] ; Jörn M. Schattenberg [Allemagne] ; Dina Tiniakos [Royaume-Uni] ; Alastair Burt [Australie] ; Elisabetta Bugianesi [Italie] ; Vlad Ratziu [France] ; Christopher P. Day [Royaume-Uni] ; Quentin M. Anstee [Royaume-Uni]Source :
- The American Journal of Gastroenterology [ 0002-9270 ] ; 2016.
Abstract
Non-invasive fibrosis scores are widely used to identify/exclude advanced fibrosis in patients with non-alcoholic fatty liver disease (NAFLD). However, these scores were principally developed and validated in patients aged between 35 and 65 years of age. The objective of this study was to assess the effect of age on the performance of non-invasive fibrosis tests in NAFLD.
Patients were recruited from European specialist hepatology clinics. The cohort was divided into five age-based groups: ≤35 (
Six hundred and thirty-four patients were included. The diagnostic accuracy of the AST/ALT ratio was lower than NFS and FIB-4 in all the age groups. The AST/ALT ratio, NFS, and FIB-4 score performed poorly for a diagnosis of advanced fibrosis in those aged ≤35 years (area under the receiver operating characteristic curves (AUROCs 0.52, 0.52, and 0.60, respectively). For all groups >35 years, AUROCs for advanced fibrosis were similar for the NFS and FIB-4 score (range 0.77–0.84). However, the specificity for advanced fibrosis using the FIB-4 and NFS declined with age, becoming unacceptably low in those aged ≥65 years (35% for FIB-4 and 20% for NFS). New cutoffs were derived (and validated) for those aged ≥65 years, which improved specificity to 70% without adversely affecting sensitivity (FIB-4 2.0, sensitivity 77% NFS 0.12, sensitivity 80%).
The NFS and FIB-4 scores have similar accuracy for advanced fibrosis in patients aged >35 years. However, the specificity for advanced fibrosis is unacceptably low in patients aged ≥65 years, resulting in a high false positive rate. New thresholds for use in patients aged ≥65 years are proposed to address this issue.
Url:
DOI: 10.1038/ajg.2016.453
PubMed: 27725647
PubMed Central: 5418560
Affiliations:
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PMC:5418560Le document en format XML
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<author><name sortKey="Romero Gomez, Manuel" sort="Romero Gomez, Manuel" uniqKey="Romero Gomez M" first="Manuel" last="Romero-Gomez">Manuel Romero-Gomez</name>
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<author><name sortKey="Oliveira, Claudia P" sort="Oliveira, Claudia P" uniqKey="Oliveira C" first="Claudia P" last="Oliveira">Claudia P. Oliveira</name>
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<author><name sortKey="Van Gaal, Luc" sort="Van Gaal, Luc" uniqKey="Van Gaal L" first="Luc" last="Van Gaal">Luc Van Gaal</name>
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<author><name sortKey="Schattenberg, Jorn M" sort="Schattenberg, Jorn M" uniqKey="Schattenberg J" first="Jörn M" last="Schattenberg">Jörn M. Schattenberg</name>
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, Turin,<country>Italy</country>
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<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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</nlm:aff>
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<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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<affiliation wicri:level="1"><nlm:aff id="aff2"><institution>Liver Unit, Newcastle Upon Tyne Hospitals NHS Trust, Freeman Hospital</institution>
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Age as a Confounding Factor for the Accurate Non-Invasive Diagnosis of Advanced NAFLD Fibrosis</title>
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</nlm:aff>
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<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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<author><name sortKey="Dufour, Jean Francois" sort="Dufour, Jean Francois" uniqKey="Dufour J" first="Jean-Francois" last="Dufour">Jean-Francois Dufour</name>
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, Berne,<country>Switzerland</country>
</nlm:aff>
<country xml:lang="fr">Suisse</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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<author><name sortKey="Petta, Salvatore" sort="Petta, Salvatore" uniqKey="Petta S" first="Salvatore" last="Petta">Salvatore Petta</name>
<affiliation wicri:level="1"><nlm:aff id="aff4"><institution>Section of Gastroenterology, Di.Bi.M.I.S., University of Palermo</institution>
, Palermo,<country>Italy</country>
</nlm:aff>
<country xml:lang="fr">Italie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Romero Gomez, Manuel" sort="Romero Gomez, Manuel" uniqKey="Romero Gomez M" first="Manuel" last="Romero-Gomez">Manuel Romero-Gomez</name>
<affiliation wicri:level="1"><nlm:aff id="aff5"><institution>UCM Digestive Diseases, Hospital Universitario Virgen Macarena-Virgen del Rocío</institution>
, Sevilla,<country>Spain</country>
</nlm:aff>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Allison, Mike" sort="Allison, Mike" uniqKey="Allison M" first="Mike" last="Allison">Mike Allison</name>
<affiliation wicri:level="1"><nlm:aff id="aff6"><institution>Liver Unit, Addenbrooke's Hospital, Cambridge Biomedical Research Centre</institution>
, Cambridge,<country>UK</country>
</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Oliveira, Claudia P" sort="Oliveira, Claudia P" uniqKey="Oliveira C" first="Claudia P" last="Oliveira">Claudia P. Oliveira</name>
<affiliation wicri:level="1"><nlm:aff id="aff7"><institution>Department of Gastroenterology, University of Sao Paulo School of Medicine</institution>
, Sao Paulo,<country>Brazil</country>
</nlm:aff>
<country xml:lang="fr">Brésil</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Francque, Sven" sort="Francque, Sven" uniqKey="Francque S" first="Sven" last="Francque">Sven Francque</name>
<affiliation wicri:level="1"><nlm:aff id="aff8"><institution>Department of Gastroenterology Hepatology, Antwerp University Hospital</institution>
, Antwerp,<country>Belgium</country>
</nlm:aff>
<country xml:lang="fr">Belgique</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Van Gaal, Luc" sort="Van Gaal, Luc" uniqKey="Van Gaal L" first="Luc" last="Van Gaal">Luc Van Gaal</name>
<affiliation wicri:level="1"><nlm:aff id="aff9"><institution>Department of Endocrinology, Diabetology and Metabolism, Antwerp University Hospital</institution>
, Antwerp,<country>Belgium</country>
</nlm:aff>
<country xml:lang="fr">Belgique</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Schattenberg, Jorn M" sort="Schattenberg, Jorn M" uniqKey="Schattenberg J" first="Jörn M" last="Schattenberg">Jörn M. Schattenberg</name>
<affiliation wicri:level="1"><nlm:aff id="aff10"><institution>Department of Medicine, University Hospital</institution>
, Mainz,<country>Germany</country>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Tiniakos, Dina" sort="Tiniakos, Dina" uniqKey="Tiniakos D" first="Dina" last="Tiniakos">Dina Tiniakos</name>
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, Newcastle upon Tyne,<country>UK</country>
</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="aff2"><institution>Liver Unit, Newcastle Upon Tyne Hospitals NHS Trust, Freeman Hospital</institution>
, Newcastle upon Tyne,<country>UK</country>
</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Burt, Alastair" sort="Burt, Alastair" uniqKey="Burt A" first="Alastair" last="Burt">Alastair Burt</name>
<affiliation wicri:level="1"><nlm:aff id="aff11"><institution>School of Medicine, University of Adelaide</institution>
, Adelaide,<country>Australia</country>
</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Bugianesi, Elisabetta" sort="Bugianesi, Elisabetta" uniqKey="Bugianesi E" first="Elisabetta" last="Bugianesi">Elisabetta Bugianesi</name>
<affiliation wicri:level="1"><nlm:aff id="aff12"><institution>Department of Medical Sciences, Division of Gastro-Hepatology, A.O. Città della Salute e della Scienza di Torino, University of Turin</institution>
, Turin,<country>Italy</country>
</nlm:aff>
<country xml:lang="fr">Italie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Ratziu, Vlad" sort="Ratziu, Vlad" uniqKey="Ratziu V" first="Vlad" last="Ratziu">Vlad Ratziu</name>
<affiliation wicri:level="1"><nlm:aff id="aff13"><institution>Institute of Cardiometabolism and Nutrition, Pitié-Salpêtrière Hospital</institution>
, Paris,<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Day, Christopher P" sort="Day, Christopher P" uniqKey="Day C" first="Christopher P" last="Day">Christopher P. Day</name>
<affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Institute of Cellular Medicine, Faculty of Medical Sciences, Newcastle University</institution>
, Newcastle upon Tyne,<country>UK</country>
</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="aff2"><institution>Liver Unit, Newcastle Upon Tyne Hospitals NHS Trust, Freeman Hospital</institution>
, Newcastle upon Tyne,<country>UK</country>
</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Anstee, Quentin M" sort="Anstee, Quentin M" uniqKey="Anstee Q" first="Quentin M" last="Anstee">Quentin M. Anstee</name>
<affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Institute of Cellular Medicine, Faculty of Medical Sciences, Newcastle University</institution>
, Newcastle upon Tyne,<country>UK</country>
</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="aff2"><institution>Liver Unit, Newcastle Upon Tyne Hospitals NHS Trust, Freeman Hospital</institution>
, Newcastle upon Tyne,<country>UK</country>
</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
</analytic>
<series><title level="j">The American Journal of Gastroenterology</title>
<idno type="ISSN">0002-9270</idno>
<idno type="eISSN">1572-0241</idno>
<imprint><date when="2016">2016</date>
</imprint>
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<front><div type="abstract" xml:lang="en"><sec><title>OBJECTIVES:</title>
<p>Non-invasive fibrosis scores are widely used to identify/exclude advanced fibrosis in patients with non-alcoholic fatty liver disease (NAFLD). However, these scores were principally developed and validated in patients aged between 35 and 65 years of age. The objective of this study was to assess the effect of age on the performance of non-invasive fibrosis tests in NAFLD.</p>
</sec>
<sec><title>METHODS:</title>
<p>Patients were recruited from European specialist hepatology clinics. The cohort was divided into five age-based groups: ≤35 (<italic>n</italic>
=74), 36–45 (<italic>n</italic>
=96), 46–55 (<italic>n</italic>
=197), 56–64 (<italic>n</italic>
=191), and ≥65 years (<italic>n</italic>
=76), and the performance of the aspartate aminotransferase (AST)/alanine transaminase (ALT) ratio, fibrosis 4 (FIB-4), and NAFLD fibrosis score (NFS) for advanced fibrosis (stage F3–F4) for each group was assessed using liver biopsy as the standard.</p>
</sec>
<sec><title>RESULTS:</title>
<p>Six hundred and thirty-four patients were included. The diagnostic accuracy of the AST/ALT ratio was lower than NFS and FIB-4 in all the age groups. The AST/ALT ratio, NFS, and FIB-4 score performed poorly for a diagnosis of advanced fibrosis in those aged ≤35 years (area under the receiver operating characteristic curves (AUROCs 0.52, 0.52, and 0.60, respectively). For all groups >35 years, AUROCs for advanced fibrosis were similar for the NFS and FIB-4 score (range 0.77–0.84). However, the specificity for advanced fibrosis using the FIB-4 and NFS declined with age, becoming unacceptably low in those aged ≥65 years (35% for FIB-4 and 20% for NFS). New cutoffs were derived (and validated) for those aged ≥65 years, which improved specificity to 70% without adversely affecting sensitivity (FIB-4 2.0, sensitivity 77% NFS 0.12, sensitivity 80%).</p>
</sec>
<sec><title>CONCLUSIONS:</title>
<p>The NFS and FIB-4 scores have similar accuracy for advanced fibrosis in patients aged >35 years. However, the specificity for advanced fibrosis is unacceptably low in patients aged ≥65 years, resulting in a high false positive rate. New thresholds for use in patients aged ≥65 years are proposed to address this issue.</p>
</sec>
</div>
</front>
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<pmc article-type="research-article"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Am J Gastroenterol</journal-id>
<journal-id journal-id-type="iso-abbrev">Am. J. Gastroenterol</journal-id>
<journal-title-group><journal-title>The American Journal of Gastroenterology</journal-title>
</journal-title-group>
<issn pub-type="ppub">0002-9270</issn>
<issn pub-type="epub">1572-0241</issn>
<publisher><publisher-name>Nature Publishing Group</publisher-name>
</publisher>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">27725647</article-id>
<article-id pub-id-type="pmc">5418560</article-id>
<article-id pub-id-type="pii">ajg2016453</article-id>
<article-id pub-id-type="doi">10.1038/ajg.2016.453</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Liver</subject>
</subj-group>
</article-categories>
<title-group><article-title>Age as a Confounding Factor for the Accurate Non-Invasive Diagnosis of Advanced NAFLD Fibrosis</article-title>
<alt-title alt-title-type="running">Effect of Age on Non-Invasive Fibrosis Scores in NAFLD</alt-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>McPherson</surname>
<given-names>Stuart</given-names>
</name>
<degrees>BSc, MBChB, MD, FRCP</degrees>
<xref ref-type="aff" rid="aff1">1</xref>
<xref ref-type="aff" rid="aff2">2</xref>
<xref ref-type="corresp" rid="caf1">*</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Hardy</surname>
<given-names>Tim</given-names>
</name>
<degrees>BSc, MBBS</degrees>
<xref ref-type="aff" rid="aff1">1</xref>
<xref ref-type="aff" rid="aff2">2</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Dufour</surname>
<given-names>Jean-Francois</given-names>
</name>
<degrees>MD, PhD</degrees>
<xref ref-type="aff" rid="aff3">3</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Petta</surname>
<given-names>Salvatore</given-names>
</name>
<degrees>MD, PhD</degrees>
<xref ref-type="aff" rid="aff4">4</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Romero-Gomez</surname>
<given-names>Manuel</given-names>
</name>
<degrees>MD, PhD</degrees>
<xref ref-type="aff" rid="aff5">5</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Allison</surname>
<given-names>Mike</given-names>
</name>
<degrees>BSc(Hons), MD, PhD</degrees>
<xref ref-type="aff" rid="aff6">6</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Oliveira</surname>
<given-names>Claudia P</given-names>
</name>
<degrees>MD, PhD</degrees>
<xref ref-type="aff" rid="aff7">7</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Francque</surname>
<given-names>Sven</given-names>
</name>
<degrees>MD, PhD</degrees>
<xref ref-type="aff" rid="aff8">8</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Van Gaal</surname>
<given-names>Luc</given-names>
</name>
<degrees>MD, PhD</degrees>
<xref ref-type="aff" rid="aff9">9</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Schattenberg</surname>
<given-names>Jörn M</given-names>
</name>
<degrees>MD, PhD</degrees>
<xref ref-type="aff" rid="aff10">10</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Tiniakos</surname>
<given-names>Dina</given-names>
</name>
<degrees>MD, PhD</degrees>
<xref ref-type="aff" rid="aff1">1</xref>
<xref ref-type="aff" rid="aff2">2</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Burt</surname>
<given-names>Alastair</given-names>
</name>
<degrees>BSc (Hons), MBChB, MD (Hons), FRCPath, FRCP, FRCPA, FRSB, F AcadMEd, FAHMS</degrees>
<xref ref-type="aff" rid="aff11">11</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Bugianesi</surname>
<given-names>Elisabetta</given-names>
</name>
<degrees>MD, PhD</degrees>
<xref ref-type="aff" rid="aff12">12</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Ratziu</surname>
<given-names>Vlad</given-names>
</name>
<degrees>MD, PhD</degrees>
<xref ref-type="aff" rid="aff13">13</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Day</surname>
<given-names>Christopher P</given-names>
</name>
<degrees>MA, MB BChir, MD, PhD, FRCP, FRCPE, FMedSci</degrees>
<xref ref-type="aff" rid="aff1">1</xref>
<xref ref-type="aff" rid="aff2">2</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Anstee</surname>
<given-names>Quentin M</given-names>
</name>
<degrees>BSc, MB BS, PhD, FRCP</degrees>
<xref ref-type="aff" rid="aff1">1</xref>
<xref ref-type="aff" rid="aff2">2</xref>
<xref ref-type="corresp" rid="caf2">*</xref>
</contrib>
<aff id="aff1"><label>1</label>
<institution>Institute of Cellular Medicine, Faculty of Medical Sciences, Newcastle University</institution>
, Newcastle upon Tyne,<country>UK</country>
</aff>
<aff id="aff2"><label>2</label>
<institution>Liver Unit, Newcastle Upon Tyne Hospitals NHS Trust, Freeman Hospital</institution>
, Newcastle upon Tyne,<country>UK</country>
</aff>
<aff id="aff3"><label>3</label>
<institution>University Clinic for Visceral Surgery and Medicine, University of Berne</institution>
, Berne,<country>Switzerland</country>
</aff>
<aff id="aff4"><label>4</label>
<institution>Section of Gastroenterology, Di.Bi.M.I.S., University of Palermo</institution>
, Palermo,<country>Italy</country>
</aff>
<aff id="aff5"><label>5</label>
<institution>UCM Digestive Diseases, Hospital Universitario Virgen Macarena-Virgen del Rocío</institution>
, Sevilla,<country>Spain</country>
</aff>
<aff id="aff6"><label>6</label>
<institution>Liver Unit, Addenbrooke's Hospital, Cambridge Biomedical Research Centre</institution>
, Cambridge,<country>UK</country>
</aff>
<aff id="aff7"><label>7</label>
<institution>Department of Gastroenterology, University of Sao Paulo School of Medicine</institution>
, Sao Paulo,<country>Brazil</country>
</aff>
<aff id="aff8"><label>8</label>
<institution>Department of Gastroenterology Hepatology, Antwerp University Hospital</institution>
, Antwerp,<country>Belgium</country>
</aff>
<aff id="aff9"><label>9</label>
<institution>Department of Endocrinology, Diabetology and Metabolism, Antwerp University Hospital</institution>
, Antwerp,<country>Belgium</country>
</aff>
<aff id="aff10"><label>10</label>
<institution>Department of Medicine, University Hospital</institution>
, Mainz,<country>Germany</country>
</aff>
<aff id="aff11"><label>11</label>
<institution>School of Medicine, University of Adelaide</institution>
, Adelaide,<country>Australia</country>
</aff>
<aff id="aff12"><label>12</label>
<institution>Department of Medical Sciences, Division of Gastro-Hepatology, A.O. Città della Salute e della Scienza di Torino, University of Turin</institution>
, Turin,<country>Italy</country>
</aff>
<aff id="aff13"><label>13</label>
<institution>Institute of Cardiometabolism and Nutrition, Pitié-Salpêtrière Hospital</institution>
, Paris,<country>France</country>
</aff>
</contrib-group>
<author-notes><corresp id="caf1"><label>*</label>
<institution>The Liver Unit, Newcastle Upon Tyne Hospitals NHS Trust, Freeman Hospital</institution>
, Level 6, Freeman Road, High Heaton, Newcastle upon Tyne NE7 7DN, <country>UK</country>
. E-mail: <email>stuart.mcpherson@nuth.nhs.uk</email>
</corresp>
<corresp id="caf2"><label>*</label>
<institution>Institute of Cellular Medicine, The Medical School, Newcastle University</institution>
, 4th Floor, William Leech Building, Framlington Place, Newcastle upon Tyne NE2 4HH, <country>UK</country>
. E-mail: <email>quentin.anstee@ncl.ac.uk</email>
</corresp>
</author-notes>
<pub-date pub-type="ppub"><month>05</month>
<year>2017</year>
</pub-date>
<pub-date pub-type="epub"><day>11</day>
<month>10</month>
<year>2016</year>
</pub-date>
<volume>112</volume>
<issue>5</issue>
<fpage>740</fpage>
<lpage>751</lpage>
<history><date date-type="received"><day>06</day>
<month>04</month>
<year>2016</year>
</date>
<date date-type="accepted"><day>03</day>
<month>07</month>
<year>2016</year>
</date>
</history>
<permissions><copyright-statement>Copyright © 2017 American College of Gastroenterology</copyright-statement>
<copyright-year>2017</copyright-year>
<copyright-holder>American College of Gastroenterology</copyright-holder>
<license license-type="open-access" xlink:href="http://creativecommons.org/licenses/by-nc-sa/4.0/"><pmc-comment>author-paid</pmc-comment>
<license-p>This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit <ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by-nc-sa/4.0/">http://creativecommons.org/licenses/by-nc-sa/4.0/</ext-link>
</license-p>
</license>
</permissions>
<abstract><sec><title>OBJECTIVES:</title>
<p>Non-invasive fibrosis scores are widely used to identify/exclude advanced fibrosis in patients with non-alcoholic fatty liver disease (NAFLD). However, these scores were principally developed and validated in patients aged between 35 and 65 years of age. The objective of this study was to assess the effect of age on the performance of non-invasive fibrosis tests in NAFLD.</p>
</sec>
<sec><title>METHODS:</title>
<p>Patients were recruited from European specialist hepatology clinics. The cohort was divided into five age-based groups: ≤35 (<italic>n</italic>
=74), 36–45 (<italic>n</italic>
=96), 46–55 (<italic>n</italic>
=197), 56–64 (<italic>n</italic>
=191), and ≥65 years (<italic>n</italic>
=76), and the performance of the aspartate aminotransferase (AST)/alanine transaminase (ALT) ratio, fibrosis 4 (FIB-4), and NAFLD fibrosis score (NFS) for advanced fibrosis (stage F3–F4) for each group was assessed using liver biopsy as the standard.</p>
</sec>
<sec><title>RESULTS:</title>
<p>Six hundred and thirty-four patients were included. The diagnostic accuracy of the AST/ALT ratio was lower than NFS and FIB-4 in all the age groups. The AST/ALT ratio, NFS, and FIB-4 score performed poorly for a diagnosis of advanced fibrosis in those aged ≤35 years (area under the receiver operating characteristic curves (AUROCs 0.52, 0.52, and 0.60, respectively). For all groups >35 years, AUROCs for advanced fibrosis were similar for the NFS and FIB-4 score (range 0.77–0.84). However, the specificity for advanced fibrosis using the FIB-4 and NFS declined with age, becoming unacceptably low in those aged ≥65 years (35% for FIB-4 and 20% for NFS). New cutoffs were derived (and validated) for those aged ≥65 years, which improved specificity to 70% without adversely affecting sensitivity (FIB-4 2.0, sensitivity 77% NFS 0.12, sensitivity 80%).</p>
</sec>
<sec><title>CONCLUSIONS:</title>
<p>The NFS and FIB-4 scores have similar accuracy for advanced fibrosis in patients aged >35 years. However, the specificity for advanced fibrosis is unacceptably low in patients aged ≥65 years, resulting in a high false positive rate. New thresholds for use in patients aged ≥65 years are proposed to address this issue.</p>
</sec>
</abstract>
</article-meta>
</front>
<floats-group><fig id="fig1"><label>Figure 1</label>
<caption><p>Plots of sensitivity and specificity against age for existing diagnostic cutoffs for advanced fibrosis for: (<bold>a</bold>
) aspartate aminotransferase (AST)/alanine transaminase (ALT) ratio (0.8); (<bold>b</bold>
) non-alcoholic fatty liver disease fibrosis score (NFS) (−1.445); (<bold>c</bold>
) fibrosis 4 (FIB-4) score (1.3). These show a reduction in sensitivity and an increase in specificity with age.</p>
</caption>
<graphic xlink:href="ajg2016453f1"></graphic>
</fig>
<fig id="fig2"><label>Figure 2</label>
<caption><p>Relationship between serum alanine transaminase (ALT) level and age in patients with (<bold>a</bold>
) stage F0–F1 fibrosis and (<bold>b</bold>
) stage F2–F4 fibrosis. Relationship between serum aspartate aminotransferase (AST) level and age in patients with (<bold>c</bold>
) stage F0–F1 fibrosis and (<bold>d</bold>
) stage F2–F4 fibrosis. A full color version of this figure is available at the <italic>American Journal of Gastroenterology</italic>
journal online.</p>
</caption>
<graphic xlink:href="ajg2016453f2"></graphic>
</fig>
<fig id="fig3"><label>Figure 3</label>
<caption><p>Plots of sensitivity and specificity against age for new diagnostic cutoffs for advanced fibrosis for: (<bold>a</bold>
) fibrosis 4 (FIB-4) score (2.0); (<bold>b</bold>
) non-alcoholic fatty liver disease fibrosis score (NFS) (0.12). Age range for which proposed thresholds are optimized is highlighted by red box. These show better specificity than current cutoffs without an adverse effect on sensitivity. A full color version of this figure is available at the <italic>American Journal of Gastroenterology</italic>
journal online.</p>
</caption>
<graphic xlink:href="ajg2016453f3"></graphic>
</fig>
<fig id="fig4"><label>Figure 4</label>
<caption><p>Proposed algorithm for the use of the (<bold>a</bold>
) non-alcoholic fatty liver disease (NAFLD) fibrosis score (NFS) and (<bold>b</bold>
) fibrosis 4 (FIB-4) score to help diagnose or exclude advanced fibrosis patients using the age specific cutoffs. The NFS and FIB-4 scores are not suitable for patients aged <35 years. Existing thresholds as previously published should be used for those aged 35–65 years. The new lower thresholds derived and validated in the current paper are recommended for those aged ≥65 years. Existing upper cutoffs remain the same for those aged ≥65 years. A full color version of this figure is available at the <italic>American Journal of Gastroenterology</italic>
journal online.</p>
</caption>
<graphic xlink:href="ajg2016453f4"></graphic>
</fig>
<table-wrap id="tbl1"><label>Table 1</label>
<caption><title>An overview of the simple non-invasive fibrosis markers under investigation (<xref ref-type="bibr" rid="bib15">15</xref>
, <xref ref-type="bibr" rid="bib16">16</xref>
, <xref ref-type="bibr" rid="bib18">18</xref>
, <xref ref-type="bibr" rid="bib19">19</xref>
, <xref ref-type="bibr" rid="bib26">26</xref>
, <xref ref-type="bibr" rid="bib27">27</xref>
)</title>
</caption>
<table frame="hsides" rules="groups" border="1"><colgroup><col align="left"></col>
<col align="center"></col>
<col align="char" char="."></col>
<col align="char" char="."></col>
</colgroup>
<thead valign="bottom"><tr><th align="left" valign="top" charoff="50"><bold>Test</bold>
</th>
<th align="center" valign="top" charoff="50"><bold>Calculation method</bold>
</th>
<th align="center" valign="top" char="." charoff="50"><bold>Lower cutoff</bold>
</th>
<th align="center" valign="top" char="." charoff="50"><bold>Upper cutoff</bold>
</th>
</tr>
</thead>
<tbody valign="top"><tr><td align="left" valign="top" charoff="50">AST/ALT ratio</td>
<td align="center" valign="top" charoff="50">AST/ALT</td>
<td align="char" valign="top" char="." charoff="50">0.8</td>
<td align="char" valign="top" char="." charoff="50">1</td>
</tr>
<tr><td align="left" valign="top" charoff="50">FIB-4 score</td>
<td align="center" valign="top" charoff="50">Age × AST (IU/l)/platelet count (× 10<sup>9</sup>
/l) × √ALT (IU/l)</td>
<td align="char" valign="top" char="." charoff="50">1.3</td>
<td align="char" valign="top" char="." charoff="50">2.67</td>
</tr>
<tr><td align="left" valign="top" charoff="50">NAFLD fibrosis score (NFS)</td>
<td align="center" valign="top" charoff="50">−1.675+0.037 × age (years)+0.094 × BMI (kg/m<sup>2</sup>
)+1.13 × impaired fasting glycemia (IFG) or diabetes (yes=1, no=0)+0.99 × AST/ALT ratio −0.013 × platelet (× 10<sup>9</sup>
/l)−0.66 × albumin (g/dl)</td>
<td align="char" valign="top" char="." charoff="50">−1.455</td>
<td align="char" valign="top" char="." charoff="50">0.676</td>
</tr>
</tbody>
</table>
<table-wrap-foot><fn id="t1-fn1"><p>ALT, alanine transaminase; AST, aspartate aminotransferase; BMI, body masss index; FIB-4, fibrosis 4; NAFLD, non-alcoholic fatty liver disease. A score below the lower cutoff is used to exclude advanced fibrosis (stage F3–F4) with reasonable accuracy and a score above the upper cutoff is suggestive of the presence of advanced fibrosis in patients with NAFLD.</p>
</fn>
</table-wrap-foot>
</table-wrap>
<table-wrap id="tbl2"><label>Table 2</label>
<caption><title>Effect of age on clinical, biochemical, and histological features in patients with NAFLD</title>
</caption>
<table frame="hsides" rules="groups" border="1"><colgroup><col align="left"></col>
<col align="char" char="±"></col>
<col align="char" char="±"></col>
<col align="char" char="±"></col>
<col align="char" char="±"></col>
<col align="char" char="±"></col>
<col align="char" char="."></col>
</colgroup>
<thead valign="bottom"><tr><th align="left" valign="top" charoff="50"><bold>Characteristics</bold>
</th>
<th align="center" valign="top" char="±" charoff="50"><bold>≤35 years,</bold>
<italic><bold>n</bold>
</italic>
<bold>=74</bold>
</th>
<th align="center" valign="top" char="±" charoff="50"><bold>36–45 years,</bold>
<italic><bold>n</bold>
</italic>
<bold>=96</bold>
</th>
<th align="center" valign="top" char="±" charoff="50"><bold>46–55 years,</bold>
<italic><bold>n</bold>
</italic>
<bold>=197</bold>
</th>
<th align="center" valign="top" char="±" charoff="50"><bold>56–64 years,</bold>
<italic><bold>n</bold>
</italic>
<bold>=191</bold>
</th>
<th align="center" valign="top" char="±" charoff="50"><bold>≥65 years,</bold>
<italic><bold>n</bold>
</italic>
<bold>=76</bold>
</th>
<th align="center" valign="top" char="." charoff="50"><italic><bold>P</bold>
</italic>
<bold>value</bold>
</th>
</tr>
</thead>
<tbody valign="top"><tr><td align="left" valign="top" charoff="50">Age (years)</td>
<td align="char" valign="top" char="±" charoff="50">28±5</td>
<td align="char" valign="top" char="±" charoff="50">41±3</td>
<td align="char" valign="top" char="±" charoff="50">51±3</td>
<td align="char" valign="top" char="±" charoff="50">60±3</td>
<td align="char" valign="top" char="±" charoff="50">69±3</td>
<td align="char" valign="top" char="." charoff="50"> </td>
</tr>
<tr><td align="left" valign="top" charoff="50">Gender (% of male)</td>
<td align="center" valign="top" char="±" charoff="50">72%</td>
<td align="center" valign="top" char="±" charoff="50">64%</td>
<td align="center" valign="top" char="±" charoff="50">57%</td>
<td align="center" valign="top" char="±" charoff="50">50%</td>
<td align="center" valign="top" char="±" charoff="50">32%</td>
<td align="char" valign="top" char="." charoff="50"><0.001<xref ref-type="fn" rid="t2-fn2">a</xref>
</td>
</tr>
<tr><td align="left" valign="top" charoff="50">BMI (kg/m<sup>2</sup>
)</td>
<td align="char" valign="top" char="±" charoff="50">34.9±6.0</td>
<td align="char" valign="top" char="±" charoff="50">35.5±6.9</td>
<td align="char" valign="top" char="±" charoff="50">34.8±6.2</td>
<td align="char" valign="top" char="±" charoff="50">34±5.2</td>
<td align="char" valign="top" char="±" charoff="50">33.6±6.3</td>
<td align="char" valign="top" char="." charoff="50">0.17<xref ref-type="fn" rid="t2-fn3">b</xref>
</td>
</tr>
<tr><td align="left" valign="top" charoff="50">Diabetes</td>
<td align="center" valign="top" char="±" charoff="50">38%</td>
<td align="center" valign="top" char="±" charoff="50">38%</td>
<td align="center" valign="top" char="±" charoff="50">41%</td>
<td align="center" valign="top" char="±" charoff="50">53%</td>
<td align="center" valign="top" char="±" charoff="50">58%</td>
<td align="char" valign="top" char="." charoff="50"><0.001<xref ref-type="fn" rid="t2-fn2">a</xref>
</td>
</tr>
<tr><td align="left" valign="top" charoff="50">ALT (IU/l)</td>
<td align="char" valign="top" char="±" charoff="50">108±72</td>
<td align="char" valign="top" char="±" charoff="50">75±45</td>
<td align="char" valign="top" char="±" charoff="50">68±45</td>
<td align="char" valign="top" char="±" charoff="50">59±33</td>
<td align="char" valign="top" char="±" charoff="50">57±40</td>
<td align="char" valign="top" char="." charoff="50"><0.001<xref ref-type="fn" rid="t2-fn3">b</xref>
</td>
</tr>
<tr><td align="left" valign="top" charoff="50">AST (IU/l)</td>
<td align="char" valign="top" char="±" charoff="50">56±33</td>
<td align="char" valign="top" char="±" charoff="50">48±33</td>
<td align="char" valign="top" char="±" charoff="50">47±32</td>
<td align="char" valign="top" char="±" charoff="50">46±24</td>
<td align="char" valign="top" char="±" charoff="50">52±42</td>
<td align="char" valign="top" char="." charoff="50">0.1<xref ref-type="fn" rid="t2-fn3">b</xref>
</td>
</tr>
<tr><td align="left" valign="top" charoff="50">ALB (g/l)</td>
<td align="char" valign="top" char="±" charoff="50">46±7</td>
<td align="char" valign="top" char="±" charoff="50">45±4</td>
<td align="char" valign="top" char="±" charoff="50">45±5</td>
<td align="char" valign="top" char="±" charoff="50">44±4</td>
<td align="char" valign="top" char="±" charoff="50">45±5</td>
<td align="char" valign="top" char="." charoff="50"><0.001<xref ref-type="fn" rid="t2-fn3">b</xref>
</td>
</tr>
<tr><td align="left" valign="top" charoff="50">Platelets (× 10<sup>9</sup>
/l)</td>
<td align="char" valign="top" char="±" charoff="50">271±63</td>
<td align="char" valign="top" char="±" charoff="50">258±77</td>
<td align="char" valign="top" char="±" charoff="50">250±66</td>
<td align="char" valign="top" char="±" charoff="50">237±67</td>
<td align="char" valign="top" char="±" charoff="50">214±84</td>
<td align="char" valign="top" char="." charoff="50"><0.001<xref ref-type="fn" rid="t2-fn3">b</xref>
</td>
</tr>
<tr><td align="left" valign="top" charoff="50">AST/ALT ratio</td>
<td align="char" valign="top" char="±" charoff="50">0.58±0.18</td>
<td align="char" valign="top" char="±" charoff="50">0.68±0.29</td>
<td align="char" valign="top" char="±" charoff="50">0.74±0.28</td>
<td align="char" valign="top" char="±" charoff="50">0.83±0.34</td>
<td align="char" valign="top" char="±" charoff="50">1.01±0.45</td>
<td align="char" valign="top" char="." charoff="50"><0.001<xref ref-type="fn" rid="t2-fn3">b</xref>
</td>
</tr>
<tr><td align="left" valign="top" charoff="50">FIB-4 score</td>
<td align="char" valign="top" char="±" charoff="50">0.59±0.25</td>
<td align="char" valign="top" char="±" charoff="50">0.98±0.62</td>
<td align="char" valign="top" char="±" charoff="50">1.24±0.72</td>
<td align="char" valign="top" char="±" charoff="50">1.70±1.1</td>
<td align="char" valign="top" char="±" charoff="50">2.94±2.98</td>
<td align="char" valign="top" char="." charoff="50"><0.001<xref ref-type="fn" rid="t2-fn3">b</xref>
</td>
</tr>
<tr><td align="left" valign="top" charoff="50">NAFLD fibrosis score</td>
<td align="char" valign="top" char="±" charoff="50">−3.20±1.14</td>
<td align="char" valign="top" char="±" charoff="50">−2.03±1.52</td>
<td align="char" valign="top" char="±" charoff="50">−1.55±1.34</td>
<td align="char" valign="top" char="±" charoff="50">−0.88±1.36</td>
<td align="char" valign="top" char="±" charoff="50">0.08±1.54</td>
<td align="char" valign="top" char="." charoff="50"><0.001<xref ref-type="fn" rid="t2-fn3">b</xref>
</td>
</tr>
<tr><td align="left" valign="top" charoff="50"><italic>Fibrosis stage</italic>
</td>
<td align="center" valign="top" char="±" charoff="50">0 (0–3)</td>
<td align="center" valign="top" char="±" charoff="50">0 (0–4)</td>
<td align="center" valign="top" char="±" charoff="50">1 (0–4)</td>
<td align="center" valign="top" char="±" charoff="50">2 (0–4)</td>
<td align="center" valign="top" char="±" charoff="50">2 (0–4)</td>
<td align="char" valign="top" char="." charoff="50"><0.001<xref ref-type="fn" rid="t2-fn4">c</xref>
</td>
</tr>
<tr><td align="left" valign="top" charoff="50"> 0</td>
<td align="center" valign="top" char="±" charoff="50">38 (51%)</td>
<td align="center" valign="top" char="±" charoff="50">50 (52%)</td>
<td align="center" valign="top" char="±" charoff="50">74 (37%)</td>
<td align="center" valign="top" char="±" charoff="50">50 (26%)</td>
<td align="center" valign="top" char="±" charoff="50">16 (21%)</td>
<td align="char" valign="top" char="." charoff="50"> </td>
</tr>
<tr><td align="left" valign="top" charoff="50"> 1</td>
<td align="center" valign="top" char="±" charoff="50">20 (27%)</td>
<td align="center" valign="top" char="±" charoff="50">19 (20%)</td>
<td align="center" valign="top" char="±" charoff="50">48 (24%)</td>
<td align="center" valign="top" char="±" charoff="50">44 (23%)</td>
<td align="center" valign="top" char="±" charoff="50">17 (22%)</td>
<td align="char" valign="top" char="." charoff="50"> </td>
</tr>
<tr><td align="left" valign="top" charoff="50"> 2</td>
<td align="center" valign="top" char="±" charoff="50">8 (11%)</td>
<td align="center" valign="top" char="±" charoff="50">9 (9%)</td>
<td align="center" valign="top" char="±" charoff="50">33 (17%)</td>
<td align="center" valign="top" char="±" charoff="50">33 (17%)</td>
<td align="center" valign="top" char="±" charoff="50">13 (17%)</td>
<td align="char" valign="top" char="." charoff="50"> </td>
</tr>
<tr><td align="left" valign="top" charoff="50"> 3</td>
<td align="center" valign="top" char="±" charoff="50">8 (11%)</td>
<td align="center" valign="top" char="±" charoff="50">15 (16%)</td>
<td align="center" valign="top" char="±" charoff="50">33 (17%)</td>
<td align="center" valign="top" char="±" charoff="50">40 (21%)</td>
<td align="center" valign="top" char="±" charoff="50">15 (20%)</td>
<td align="char" valign="top" char="." charoff="50"> </td>
</tr>
<tr><td align="left" valign="top" charoff="50"> 4</td>
<td align="center" valign="top" char="±" charoff="50">0 (0%)</td>
<td align="center" valign="top" char="±" charoff="50">3 (3%)</td>
<td align="center" valign="top" char="±" charoff="50">9 (5%)</td>
<td align="center" valign="top" char="±" charoff="50">24 (13%)</td>
<td align="center" valign="top" char="±" charoff="50">15 (20%)</td>
<td align="char" valign="top" char="." charoff="50"> </td>
</tr>
<tr><td align="left" valign="top" charoff="50">Stage F3 or F4 fibrosis</td>
<td align="center" valign="top" char="±" charoff="50">8 (11%)</td>
<td align="center" valign="top" char="±" charoff="50">18 (19%)</td>
<td align="center" valign="top" char="±" charoff="50">42 (22%)</td>
<td align="center" valign="top" char="±" charoff="50">64 (34%)</td>
<td align="center" valign="top" char="±" charoff="50">30 (40%)</td>
<td align="char" valign="top" char="." charoff="50"><0.001<xref ref-type="fn" rid="t2-fn2">a</xref>
</td>
</tr>
<tr><td align="left" valign="top" charoff="50">NASH</td>
<td align="center" valign="top" char="±" charoff="50">45 (61%)</td>
<td align="center" valign="top" char="±" charoff="50">61 (64%)</td>
<td align="center" valign="top" char="±" charoff="50">141 (72%)</td>
<td align="center" valign="top" char="±" charoff="50">154 (81%)</td>
<td align="center" valign="top" char="±" charoff="50">60 (79%)</td>
<td align="char" valign="top" char="." charoff="50">0.002<xref ref-type="fn" rid="t2-fn2">a</xref>
</td>
</tr>
<tr><td align="left" valign="top" charoff="50">NAS</td>
<td align="center" valign="top" char="±" charoff="50">4 (1–7)</td>
<td align="center" valign="top" char="±" charoff="50">4 (1–7)</td>
<td align="center" valign="top" char="±" charoff="50">4 (1–8)</td>
<td align="center" valign="top" char="±" charoff="50">4 (1–8)</td>
<td align="center" valign="top" char="±" charoff="50">3 (1–7)</td>
<td align="char" valign="top" char="." charoff="50">0.24<xref ref-type="fn" rid="t2-fn4">c</xref>
</td>
</tr>
<tr><td align="left" valign="top" charoff="50">Raised transaminases</td>
<td align="center" valign="top" char="±" charoff="50">62 (84%)</td>
<td align="center" valign="top" char="±" charoff="50">74 (77%)</td>
<td align="center" valign="top" char="±" charoff="50">142 (72%)</td>
<td align="center" valign="top" char="±" charoff="50">137 (72%)</td>
<td align="center" valign="top" char="±" charoff="50">49 (64%)</td>
<td align="char" valign="top" char="." charoff="50">0.083<xref ref-type="fn" rid="t2-fn2">a</xref>
</td>
</tr>
</tbody>
</table>
<table-wrap-foot><fn id="t2-fn1"><p>ALB, albumin; ALT, alanine transaminase; AST, aspartate aminotransferase; BMI, body masss index; FIB-4, fibrosis 4; NAFLD, non-alcoholic fatty liver disease; NAS, NAFLD Activity Score; NASH, non-alcoholic steatohepatitis. Data are expressed as mean±s.d. or median (range). Raised transaminases=serum ALT or AST >40 IU/l.</p>
</fn>
<fn id="t2-fn2"><label>a</label>
<p>Chi-square test.</p>
</fn>
<fn id="t2-fn3"><label>b</label>
<p>Student's <italic>t</italic>
-test.</p>
</fn>
<fn id="t2-fn4"><label>c</label>
<p>Mann–Whitney <italic>U</italic>
-test.</p>
</fn>
</table-wrap-foot>
</table-wrap>
<table-wrap id="tbl3"><label>Table 3</label>
<caption><title>Performance of the tests for diagnosis/exclusion of advanced fibrosis by age group using established cutoffs (<xref ref-type="bibr" rid="bib15">15</xref>
, <xref ref-type="bibr" rid="bib16">16</xref>
, <xref ref-type="bibr" rid="bib18">18</xref>
, <xref ref-type="bibr" rid="bib19">19</xref>
)</title>
</caption>
<table frame="hsides" rules="groups" border="1"><colgroup><col align="left"></col>
<col align="char" char="("></col>
<col align="char" char="."></col>
<col align="char" char="."></col>
<col align="char" char="."></col>
<col align="char" char="."></col>
<col align="char" char="."></col>
<col align="char" char="."></col>
<col align="char" char="."></col>
</colgroup>
<thead valign="bottom"><tr><th align="left" valign="top" charoff="50"><bold>Test</bold>
</th>
<th align="center" valign="top" char="(" charoff="50"><bold>AUROC (95% CI)</bold>
</th>
<th align="center" valign="top" char="." charoff="50"><bold>Cutoff</bold>
</th>
<th align="center" valign="top" char="." charoff="50"><bold>Sens. (%)</bold>
</th>
<th align="center" valign="top" char="." charoff="50"><bold>Spec. (%)</bold>
</th>
<th align="center" valign="top" char="." charoff="50"><bold>PPV (%)</bold>
</th>
<th align="center" valign="top" char="." charoff="50"><bold>NPV (%)</bold>
</th>
<th align="center" valign="top" char="." charoff="50"><bold>LR +ve</bold>
</th>
<th align="center" valign="top" char="." charoff="50"><bold>LR −ve</bold>
</th>
</tr>
</thead>
<tbody valign="top"><tr><td colspan="9" align="left" valign="top" charoff="50"><italic>≤35 years</italic>
</td>
</tr>
<tr><td align="left" valign="top" charoff="50"> AST/ALT ratio</td>
<td align="char" valign="top" char="(" charoff="50">0.52 (0.29–0.75)</td>
<td align="char" valign="top" char="." charoff="50">0.8</td>
<td align="char" valign="top" char="." charoff="50">25</td>
<td align="char" valign="top" char="." charoff="50">89</td>
<td align="char" valign="top" char="." charoff="50">22</td>
<td align="char" valign="top" char="." charoff="50">91</td>
<td align="char" valign="top" char="." charoff="50">2.27</td>
<td align="char" valign="top" char="." charoff="50">0.84</td>
</tr>
<tr><td align="left" valign="top" charoff="50"> </td>
<td align="char" valign="top" char="(" charoff="50"> </td>
<td align="char" valign="top" char="." charoff="50">1</td>
<td align="char" valign="top" char="." charoff="50">0</td>
<td align="char" valign="top" char="." charoff="50">98.5</td>
<td align="char" valign="top" char="." charoff="50">0</td>
<td align="char" valign="top" char="." charoff="50">89</td>
<td align="char" valign="top" char="." charoff="50">0</td>
<td align="char" valign="top" char="." charoff="50">0.13</td>
</tr>
<tr><td align="left" valign="top" charoff="50"> FIB-4 score</td>
<td align="char" valign="top" char="(" charoff="50">0.60 (0.40–0.81)</td>
<td align="char" valign="top" char="." charoff="50">1.30</td>
<td align="char" valign="top" char="." charoff="50">0</td>
<td align="char" valign="top" char="." charoff="50">97</td>
<td align="char" valign="top" char="." charoff="50">0</td>
<td align="char" valign="top" char="." charoff="50">89</td>
<td align="char" valign="top" char="." charoff="50">0</td>
<td align="char" valign="top" char="." charoff="50">1.03</td>
</tr>
<tr><td align="left" valign="top" charoff="50"> </td>
<td align="char" valign="top" char="(" charoff="50"> </td>
<td align="char" valign="top" char="." charoff="50">2.67</td>
<td align="char" valign="top" char="." charoff="50">0</td>
<td align="char" valign="top" char="." charoff="50">100</td>
<td align="char" valign="top" char="." charoff="50">0</td>
<td align="char" valign="top" char="." charoff="50">89</td>
<td align="center" valign="top" char="." charoff="50">—</td>
<td align="char" valign="top" char="." charoff="50">1</td>
</tr>
<tr><td align="left" valign="top" charoff="50"> </td>
<td align="char" valign="top" char="(" charoff="50"> </td>
<td align="char" valign="top" char="." charoff="50">3.25</td>
<td align="char" valign="top" char="." charoff="50">0</td>
<td align="char" valign="top" char="." charoff="50">100</td>
<td align="char" valign="top" char="." charoff="50">0</td>
<td align="char" valign="top" char="." charoff="50">89</td>
<td align="center" valign="top" char="." charoff="50">—</td>
<td align="char" valign="top" char="." charoff="50">1</td>
</tr>
<tr><td align="left" valign="top" charoff="50"> NFS</td>
<td align="char" valign="top" char="(" charoff="50">0.52 (0.32–0.73)</td>
<td align="char" valign="top" char="." charoff="50">−1.455</td>
<td align="char" valign="top" char="." charoff="50">0</td>
<td align="char" valign="top" char="." charoff="50">91</td>
<td align="char" valign="top" char="." charoff="50">0</td>
<td align="char" valign="top" char="." charoff="50">88</td>
<td align="center" valign="top" char="." charoff="50">—</td>
<td align="char" valign="top" char="." charoff="50">1</td>
</tr>
<tr><td align="left" valign="top" charoff="50"> </td>
<td align="char" valign="top" char="(" charoff="50"> </td>
<td align="char" valign="top" char="." charoff="50">0.676</td>
<td align="char" valign="top" char="." charoff="50">0</td>
<td align="char" valign="top" char="." charoff="50">100</td>
<td align="char" valign="top" char="." charoff="50">0</td>
<td align="char" valign="top" char="." charoff="50">89</td>
<td align="center" valign="top" char="." charoff="50">—</td>
<td align="char" valign="top" char="." charoff="50">1</td>
</tr>
<tr><td colspan="9" align="left" valign="top" charoff="50"><italic>36–45 years</italic>
</td>
</tr>
<tr><td align="left" valign="top" charoff="50"> AST/ALT ratio</td>
<td align="char" valign="top" char="(" charoff="50">0.66 (0.53–0.80)</td>
<td align="char" valign="top" char="." charoff="50">0.8</td>
<td align="char" valign="top" char="." charoff="50">39</td>
<td align="char" valign="top" char="." charoff="50">80</td>
<td align="char" valign="top" char="." charoff="50">31</td>
<td align="char" valign="top" char="." charoff="50">85</td>
<td align="char" valign="top" char="." charoff="50">1.95</td>
<td align="char" valign="top" char="." charoff="50">0.76</td>
</tr>
<tr><td align="left" valign="top" charoff="50"> </td>
<td align="char" valign="top" char="(" charoff="50"> </td>
<td align="char" valign="top" char="." charoff="50">1</td>
<td align="char" valign="top" char="." charoff="50">6</td>
<td align="char" valign="top" char="." charoff="50">94</td>
<td align="char" valign="top" char="." charoff="50">19</td>
<td align="char" valign="top" char="." charoff="50">81</td>
<td align="char" valign="top" char="." charoff="50">1</td>
<td align="char" valign="top" char="." charoff="50">1</td>
</tr>
<tr><td align="left" valign="top" charoff="50"> FIB-4 score</td>
<td align="char" valign="top" char="(" charoff="50">0.79 (0.66–0.91)</td>
<td align="char" valign="top" char="." charoff="50">1.30</td>
<td align="char" valign="top" char="." charoff="50">56</td>
<td align="char" valign="top" char="." charoff="50">91</td>
<td align="char" valign="top" char="." charoff="50">59</td>
<td align="char" valign="top" char="." charoff="50">90</td>
<td align="char" valign="top" char="." charoff="50">6.2</td>
<td align="char" valign="top" char="." charoff="50">0.48</td>
</tr>
<tr><td align="left" valign="top" charoff="50"> </td>
<td align="char" valign="top" char="(" charoff="50"> </td>
<td align="char" valign="top" char="." charoff="50">2.67</td>
<td align="char" valign="top" char="." charoff="50">17</td>
<td align="char" valign="top" char="." charoff="50">100</td>
<td align="char" valign="top" char="." charoff="50">100</td>
<td align="char" valign="top" char="." charoff="50">84</td>
<td align="char" valign="top" char="." charoff="50">∞</td>
<td align="char" valign="top" char="." charoff="50">0.83</td>
</tr>
<tr><td align="left" valign="top" charoff="50"> </td>
<td align="char" valign="top" char="(" charoff="50"> </td>
<td align="char" valign="top" char="." charoff="50">3.25</td>
<td align="char" valign="top" char="." charoff="50">6</td>
<td align="char" valign="top" char="." charoff="50">100</td>
<td align="char" valign="top" char="." charoff="50">100</td>
<td align="char" valign="top" char="." charoff="50">82</td>
<td align="char" valign="top" char="." charoff="50">∞</td>
<td align="char" valign="top" char="." charoff="50">0.94</td>
</tr>
<tr><td align="left" valign="top" charoff="50"> NFS</td>
<td align="char" valign="top" char="(" charoff="50">0.86 (0.76–0.96)</td>
<td align="char" valign="top" char="." charoff="50">−1.455</td>
<td align="char" valign="top" char="." charoff="50">78</td>
<td align="char" valign="top" char="." charoff="50">80</td>
<td align="char" valign="top" char="." charoff="50">48</td>
<td align="char" valign="top" char="." charoff="50">94</td>
<td align="char" valign="top" char="." charoff="50">3.9</td>
<td align="char" valign="top" char="." charoff="50">0.28</td>
</tr>
<tr><td align="left" valign="top" charoff="50"> </td>
<td align="char" valign="top" char="(" charoff="50"> </td>
<td align="char" valign="top" char="." charoff="50">0.676</td>
<td align="char" valign="top" char="." charoff="50">22</td>
<td align="char" valign="top" char="." charoff="50">100</td>
<td align="char" valign="top" char="." charoff="50">100</td>
<td align="char" valign="top" char="." charoff="50">85</td>
<td align="center" valign="top" char="." charoff="50">∞</td>
<td align="char" valign="top" char="." charoff="50">0.78</td>
</tr>
<tr><td colspan="9" align="left" valign="top" charoff="50"><italic>46–55 years</italic>
</td>
</tr>
<tr><td align="left" valign="top" charoff="50"> AST/ALT ratio</td>
<td align="char" valign="top" char="(" charoff="50">0.63 (0.53–0.73)</td>
<td align="char" valign="top" char="." charoff="50">0.8</td>
<td align="char" valign="top" char="." charoff="50">44</td>
<td align="char" valign="top" char="." charoff="50">74</td>
<td align="char" valign="top" char="." charoff="50">31</td>
<td align="char" valign="top" char="." charoff="50">83</td>
<td align="char" valign="top" char="." charoff="50">1.69</td>
<td align="char" valign="top" char="." charoff="50">0.76</td>
</tr>
<tr><td align="left" valign="top" charoff="50"> </td>
<td align="char" valign="top" char="(" charoff="50"> </td>
<td align="char" valign="top" char="." charoff="50">1</td>
<td align="char" valign="top" char="." charoff="50">20</td>
<td align="char" valign="top" char="." charoff="50">91</td>
<td align="char" valign="top" char="." charoff="50">37</td>
<td align="char" valign="top" char="." charoff="50">81</td>
<td align="char" valign="top" char="." charoff="50">2.22</td>
<td align="char" valign="top" char="." charoff="50">0.88</td>
</tr>
<tr><td align="left" valign="top" charoff="50"> FIB-4 score</td>
<td align="char" valign="top" char="(" charoff="50">0.77 (0.68–0.86)</td>
<td align="char" valign="top" char="." charoff="50">1.30</td>
<td align="char" valign="top" char="." charoff="50">63</td>
<td align="char" valign="top" char="." charoff="50">77</td>
<td align="char" valign="top" char="." charoff="50">42</td>
<td align="char" valign="top" char="." charoff="50">89</td>
<td align="char" valign="top" char="." charoff="50">2.74</td>
<td align="char" valign="top" char="." charoff="50">0.48</td>
</tr>
<tr><td align="left" valign="top" charoff="50"> </td>
<td align="char" valign="top" char="(" charoff="50"> </td>
<td align="char" valign="top" char="." charoff="50">2.67</td>
<td align="char" valign="top" char="." charoff="50">12</td>
<td align="char" valign="top" char="." charoff="50">98.7</td>
<td align="char" valign="top" char="." charoff="50">71</td>
<td align="char" valign="top" char="." charoff="50">81</td>
<td align="char" valign="top" char="." charoff="50">9.23</td>
<td align="char" valign="top" char="." charoff="50">0.89</td>
</tr>
<tr><td align="left" valign="top" charoff="50"> </td>
<td align="char" valign="top" char="(" charoff="50"> </td>
<td align="char" valign="top" char="." charoff="50">3.25</td>
<td align="char" valign="top" char="." charoff="50">5</td>
<td align="char" valign="top" char="." charoff="50">99.9</td>
<td align="char" valign="top" char="." charoff="50">93</td>
<td align="char" valign="top" char="." charoff="50">80</td>
<td align="char" valign="top" char="." charoff="50">50</td>
<td align="char" valign="top" char="." charoff="50">0.95</td>
</tr>
<tr><td align="left" valign="top" charoff="50"> NFS</td>
<td align="char" valign="top" char="(" charoff="50">0.81 (0.73–0.89)</td>
<td align="char" valign="top" char="." charoff="50">−1.455</td>
<td align="char" valign="top" char="." charoff="50">81</td>
<td align="char" valign="top" char="." charoff="50">65</td>
<td align="char" valign="top" char="." charoff="50">38</td>
<td align="char" valign="top" char="." charoff="50">93</td>
<td align="char" valign="top" char="." charoff="50">2.31</td>
<td align="char" valign="top" char="." charoff="50">0.29</td>
</tr>
<tr><td align="left" valign="top" charoff="50"> </td>
<td align="char" valign="top" char="(" charoff="50"> </td>
<td align="char" valign="top" char="." charoff="50">0.676</td>
<td align="char" valign="top" char="." charoff="50">22</td>
<td align="char" valign="top" char="." charoff="50">97.4</td>
<td align="char" valign="top" char="." charoff="50">69</td>
<td align="char" valign="top" char="." charoff="50">82</td>
<td align="char" valign="top" char="." charoff="50">8.46</td>
<td align="char" valign="top" char="." charoff="50">0.8</td>
</tr>
<tr><td colspan="9" align="left" valign="top" charoff="50"><italic>56–64 years</italic>
</td>
</tr>
<tr><td align="left" valign="top" charoff="50"> AST/ALT ratio</td>
<td align="char" valign="top" char="(" charoff="50">0.72 (0.64–0.80)</td>
<td align="char" valign="top" char="." charoff="50">0.8</td>
<td align="char" valign="top" char="." charoff="50">64</td>
<td align="char" valign="top" char="." charoff="50">69</td>
<td align="char" valign="top" char="." charoff="50">52</td>
<td align="char" valign="top" char="." charoff="50">79</td>
<td align="char" valign="top" char="." charoff="50">2.06</td>
<td align="char" valign="top" char="." charoff="50">0.52</td>
</tr>
<tr><td align="left" valign="top" charoff="50"> </td>
<td align="char" valign="top" char="(" charoff="50"> </td>
<td align="char" valign="top" char="." charoff="50">1</td>
<td align="char" valign="top" char="." charoff="50">38</td>
<td align="char" valign="top" char="." charoff="50">92</td>
<td align="char" valign="top" char="." charoff="50">71</td>
<td align="char" valign="top" char="." charoff="50">74</td>
<td align="char" valign="top" char="." charoff="50">4.75</td>
<td align="char" valign="top" char="." charoff="50">0.67</td>
</tr>
<tr><td align="left" valign="top" charoff="50"> FIB-4 score</td>
<td align="char" valign="top" char="(" charoff="50">0.84 (0.78–0.90)</td>
<td align="char" valign="top" char="." charoff="50">1.30</td>
<td align="char" valign="top" char="." charoff="50">90</td>
<td align="char" valign="top" char="." charoff="50">61</td>
<td align="char" valign="top" char="." charoff="50">54</td>
<td align="char" valign="top" char="." charoff="50">92</td>
<td align="char" valign="top" char="." charoff="50">2.3</td>
<td align="char" valign="top" char="." charoff="50">0.16</td>
</tr>
<tr><td align="left" valign="top" charoff="50"> </td>
<td align="char" valign="top" char="(" charoff="50"> </td>
<td align="char" valign="top" char="." charoff="50">2.67</td>
<td align="char" valign="top" char="." charoff="50">30</td>
<td align="char" valign="top" char="." charoff="50">97.6</td>
<td align="char" valign="top" char="." charoff="50">86</td>
<td align="char" valign="top" char="." charoff="50">73</td>
<td align="char" valign="top" char="." charoff="50">12.5</td>
<td align="char" valign="top" char="." charoff="50">0.72</td>
</tr>
<tr><td align="left" valign="top" charoff="50"> </td>
<td align="char" valign="top" char="(" charoff="50"> </td>
<td align="char" valign="top" char="." charoff="50">3.25</td>
<td align="char" valign="top" char="." charoff="50">20</td>
<td align="char" valign="top" char="." charoff="50">100</td>
<td align="char" valign="top" char="." charoff="50">100</td>
<td align="char" valign="top" char="." charoff="50">71</td>
<td align="center" valign="top" char="." charoff="50">∞</td>
<td align="char" valign="top" char="." charoff="50">0.8</td>
</tr>
<tr><td align="left" valign="top" charoff="50"> NFS</td>
<td align="char" valign="top" char="(" charoff="50">0.83 (0.64–0.80)</td>
<td align="char" valign="top" char="." charoff="50">−1.455</td>
<td align="char" valign="top" char="." charoff="50">95</td>
<td align="char" valign="top" char="." charoff="50">44</td>
<td align="char" valign="top" char="." charoff="50">47</td>
<td align="char" valign="top" char="." charoff="50">94</td>
<td align="char" valign="top" char="." charoff="50">1.69</td>
<td align="char" valign="top" char="." charoff="50">0.11</td>
</tr>
<tr><td align="left" valign="top" charoff="50"> </td>
<td align="char" valign="top" char="(" charoff="50"> </td>
<td align="char" valign="top" char="." charoff="50">0.676</td>
<td align="char" valign="top" char="." charoff="50">31</td>
<td align="char" valign="top" char="." charoff="50">99.9</td>
<td align="char" valign="top" char="." charoff="50">99</td>
<td align="char" valign="top" char="." charoff="50">74</td>
<td align="char" valign="top" char="." charoff="50">310</td>
<td align="char" valign="top" char="." charoff="50">0.69</td>
</tr>
<tr><td colspan="9" align="left" valign="top" charoff="50"><italic>≥65 years</italic>
</td>
</tr>
<tr><td align="left" valign="top" charoff="50"> AST/ALT ratio</td>
<td align="char" valign="top" char="(" charoff="50">0.73 (0.61–0.85)</td>
<td align="char" valign="top" char="." charoff="50">0.8</td>
<td align="char" valign="top" char="." charoff="50">80</td>
<td align="char" valign="top" char="." charoff="50">48</td>
<td align="char" valign="top" char="." charoff="50">50</td>
<td align="char" valign="top" char="." charoff="50">79</td>
<td align="char" valign="top" char="." charoff="50">1.53</td>
<td align="char" valign="top" char="." charoff="50">0.42</td>
</tr>
<tr><td align="left" valign="top" charoff="50"> </td>
<td align="char" valign="top" char="(" charoff="50"> </td>
<td align="char" valign="top" char="." charoff="50">1</td>
<td align="char" valign="top" char="." charoff="50">67</td>
<td align="char" valign="top" char="." charoff="50">76</td>
<td align="char" valign="top" char="." charoff="50">64</td>
<td align="char" valign="top" char="." charoff="50">78</td>
<td align="char" valign="top" char="." charoff="50">2.79</td>
<td align="char" valign="top" char="." charoff="50">0.43</td>
</tr>
<tr><td align="left" valign="top" charoff="50"> FIB-4 score</td>
<td align="char" valign="top" char="(" charoff="50">0.81 (0.72–0.91)</td>
<td align="char" valign="top" char="." charoff="50">1.30</td>
<td align="char" valign="top" char="." charoff="50">93</td>
<td align="char" valign="top" char="." charoff="50">35</td>
<td align="char" valign="top" char="." charoff="50">48</td>
<td align="char" valign="top" char="." charoff="50">89</td>
<td align="char" valign="top" char="." charoff="50">1.43</td>
<td align="char" valign="top" char="." charoff="50">0.2</td>
</tr>
<tr><td align="left" valign="top" charoff="50"> </td>
<td align="char" valign="top" char="(" charoff="50"> </td>
<td align="char" valign="top" char="." charoff="50">2.67</td>
<td align="char" valign="top" char="." charoff="50">53</td>
<td align="char" valign="top" char="." charoff="50">85</td>
<td align="char" valign="top" char="." charoff="50">69</td>
<td align="char" valign="top" char="." charoff="50">74</td>
<td align="char" valign="top" char="." charoff="50">3.53</td>
<td align="char" valign="top" char="." charoff="50">0.55</td>
</tr>
<tr><td align="left" valign="top" charoff="50"> </td>
<td align="char" valign="top" char="(" charoff="50"> </td>
<td align="char" valign="top" char="." charoff="50">3.25</td>
<td align="char" valign="top" char="." charoff="50">50</td>
<td align="char" valign="top" char="." charoff="50">91</td>
<td align="char" valign="top" char="." charoff="50">78</td>
<td align="char" valign="top" char="." charoff="50">74</td>
<td align="char" valign="top" char="." charoff="50">5.55</td>
<td align="char" valign="top" char="." charoff="50">0.55</td>
</tr>
<tr><td align="left" valign="top" charoff="50"> NFS</td>
<td align="char" valign="top" char="(" charoff="50">0.81 (0.71–0.92)</td>
<td align="char" valign="top" char="." charoff="50">−1.455</td>
<td align="char" valign="top" char="." charoff="50">93</td>
<td align="char" valign="top" char="." charoff="50">20</td>
<td align="char" valign="top" char="." charoff="50">43</td>
<td align="char" valign="top" char="." charoff="50">82</td>
<td align="char" valign="top" char="." charoff="50">1.16</td>
<td align="char" valign="top" char="." charoff="50">0.35</td>
</tr>
<tr><td align="left" valign="top" charoff="50"> </td>
<td align="char" valign="top" char="(" charoff="50"> </td>
<td align="char" valign="top" char="." charoff="50">0.676</td>
<td align="char" valign="top" char="." charoff="50">57</td>
<td align="char" valign="top" char="." charoff="50">85</td>
<td align="char" valign="top" char="." charoff="50">71</td>
<td align="char" valign="top" char="." charoff="50">76</td>
<td align="char" valign="top" char="." charoff="50">3.8</td>
<td align="char" valign="top" char="." charoff="50">0.51</td>
</tr>
</tbody>
</table>
<table-wrap-foot><fn id="t3-fn1"><p>ALT, alanine transaminase; AST, aspartate aminotransferase; AUROC, area under the receiver operating characteristic curve; CI, confidence interval; FIB-4, fibrosis 4; LR +ve, positive likelihood ratio, LR −ve, negative likelihood ratio; NFS, non-alcoholic fatty liver disease fibrosis score; NPV, negative predictive value; PPV, positive predictive value; Sens., sensitivity; Spec., specificity.</p>
</fn>
</table-wrap-foot>
</table-wrap>
<table-wrap id="tbl4"><label>Table 4</label>
<caption><title>Performance of current and proposed new cutoffs to exclude advanced fibrosis (stage F3–F4) in older patients (≥65 years) at different prevalence rates of advanced fibrosis</title>
</caption>
<table frame="hsides" rules="groups" border="1"><colgroup><col align="left"></col>
<col align="char" char="."></col>
<col align="char" char="."></col>
<col align="char" char="."></col>
<col align="char" char="."></col>
<col align="char" char="."></col>
<col align="char" char="."></col>
<col align="char" char="."></col>
<col align="char" char="."></col>
</colgroup>
<thead valign="bottom"><tr><th align="left" valign="top" charoff="50"><bold>Test</bold>
</th>
<th align="center" valign="top" char="." charoff="50"><bold>Cutoff</bold>
</th>
<th align="center" valign="top" char="." charoff="50"><bold>Sens. (%)</bold>
</th>
<th align="center" valign="top" char="." charoff="50"><bold>Spec. (%)</bold>
</th>
<th align="center" valign="top" char="." charoff="50"><bold>Prev. (%)</bold>
</th>
<th align="center" valign="top" char="." charoff="50"><bold>PPV (%)</bold>
</th>
<th align="center" valign="top" char="." charoff="50"><bold>NPV (%)</bold>
</th>
<th align="center" valign="top" char="." charoff="50"><bold>LR +ve</bold>
</th>
<th align="center" valign="top" char="." charoff="50"><bold>LR −ve</bold>
</th>
</tr>
</thead>
<tbody valign="top"><tr><td align="left" valign="top" charoff="50">FIB-4</td>
<td align="char" valign="top" char="." charoff="50">1.3</td>
<td align="char" valign="top" char="." charoff="50">93</td>
<td align="char" valign="top" char="." charoff="50">35</td>
<td align="char" valign="top" char="." charoff="50">5</td>
<td align="char" valign="top" char="." charoff="50">7</td>
<td align="char" valign="top" char="." charoff="50">99</td>
<td align="char" valign="top" char="." charoff="50">1.43</td>
<td align="char" valign="top" char="." charoff="50">0.2</td>
</tr>
<tr><td align="left" valign="top" charoff="50"> </td>
<td align="char" valign="top" char="." charoff="50"> </td>
<td align="char" valign="top" char="." charoff="50"> </td>
<td align="char" valign="top" char="." charoff="50"> </td>
<td align="char" valign="top" char="." charoff="50">10</td>
<td align="char" valign="top" char="." charoff="50">14</td>
<td align="char" valign="top" char="." charoff="50">98</td>
<td align="char" valign="top" char="." charoff="50"> </td>
<td align="char" valign="top" char="." charoff="50"> </td>
</tr>
<tr><td align="left" valign="top" charoff="50"> </td>
<td align="char" valign="top" char="." charoff="50"> </td>
<td align="char" valign="top" char="." charoff="50"> </td>
<td align="char" valign="top" char="." charoff="50"> </td>
<td align="char" valign="top" char="." charoff="50">20</td>
<td align="char" valign="top" char="." charoff="50">26</td>
<td align="char" valign="top" char="." charoff="50">95</td>
<td align="char" valign="top" char="." charoff="50"> </td>
<td align="char" valign="top" char="." charoff="50"> </td>
</tr>
<tr><td align="left" valign="top" charoff="50"> </td>
<td align="char" valign="top" char="." charoff="50"> </td>
<td align="char" valign="top" char="." charoff="50"> </td>
<td align="char" valign="top" char="." charoff="50"> </td>
<td align="char" valign="top" char="." charoff="50">30</td>
<td align="char" valign="top" char="." charoff="50">38</td>
<td align="char" valign="top" char="." charoff="50">92</td>
<td align="char" valign="top" char="." charoff="50"> </td>
<td align="char" valign="top" char="." charoff="50"> </td>
</tr>
<tr><td align="left" valign="top" charoff="50"> </td>
<td align="char" valign="top" char="." charoff="50"> </td>
<td align="char" valign="top" char="." charoff="50"> </td>
<td align="char" valign="top" char="." charoff="50"> </td>
<td align="char" valign="top" char="." charoff="50">40</td>
<td align="char" valign="top" char="." charoff="50">49</td>
<td align="char" valign="top" char="." charoff="50">88</td>
<td align="char" valign="top" char="." charoff="50"> </td>
<td align="char" valign="top" char="." charoff="50"> </td>
</tr>
<tr><td align="left" valign="top" charoff="50"> </td>
<td align="char" valign="top" char="." charoff="50">2.0</td>
<td align="char" valign="top" char="." charoff="50">77</td>
<td align="char" valign="top" char="." charoff="50">70</td>
<td align="char" valign="top" char="." charoff="50">5</td>
<td align="char" valign="top" char="." charoff="50">12</td>
<td align="char" valign="top" char="." charoff="50">98</td>
<td align="char" valign="top" char="." charoff="50">2.56</td>
<td align="char" valign="top" char="." charoff="50">0.33</td>
</tr>
<tr><td align="left" valign="top" charoff="50"> </td>
<td align="char" valign="top" char="." charoff="50"> </td>
<td align="char" valign="top" char="." charoff="50"> </td>
<td align="char" valign="top" char="." charoff="50"> </td>
<td align="char" valign="top" char="." charoff="50">10</td>
<td align="char" valign="top" char="." charoff="50">22</td>
<td align="char" valign="top" char="." charoff="50">96</td>
<td align="char" valign="top" char="." charoff="50"> </td>
<td align="char" valign="top" char="." charoff="50"> </td>
</tr>
<tr><td align="left" valign="top" charoff="50"> </td>
<td align="char" valign="top" char="." charoff="50"> </td>
<td align="char" valign="top" char="." charoff="50"> </td>
<td align="char" valign="top" char="." charoff="50"> </td>
<td align="char" valign="top" char="." charoff="50">20</td>
<td align="char" valign="top" char="." charoff="50">39</td>
<td align="char" valign="top" char="." charoff="50">92</td>
<td align="char" valign="top" char="." charoff="50"> </td>
<td align="char" valign="top" char="." charoff="50"> </td>
</tr>
<tr><td align="left" valign="top" charoff="50"> </td>
<td align="char" valign="top" char="." charoff="50"> </td>
<td align="char" valign="top" char="." charoff="50"> </td>
<td align="char" valign="top" char="." charoff="50"> </td>
<td align="char" valign="top" char="." charoff="50">30</td>
<td align="char" valign="top" char="." charoff="50">52</td>
<td align="char" valign="top" char="." charoff="50">88</td>
<td align="char" valign="top" char="." charoff="50"> </td>
<td align="char" valign="top" char="." charoff="50"> </td>
</tr>
<tr><td align="left" valign="top" charoff="50"> </td>
<td align="char" valign="top" char="." charoff="50"> </td>
<td align="char" valign="top" char="." charoff="50"> </td>
<td align="char" valign="top" char="." charoff="50"> </td>
<td align="char" valign="top" char="." charoff="50">40</td>
<td align="char" valign="top" char="." charoff="50">63</td>
<td align="char" valign="top" char="." charoff="50">82</td>
<td align="char" valign="top" char="." charoff="50"> </td>
<td align="char" valign="top" char="." charoff="50"> </td>
</tr>
<tr><td align="left" valign="top" charoff="50">NFS</td>
<td align="char" valign="top" char="." charoff="50">−1.455</td>
<td align="char" valign="top" char="." charoff="50">93</td>
<td align="char" valign="top" char="." charoff="50">20</td>
<td align="char" valign="top" char="." charoff="50">5</td>
<td align="char" valign="top" char="." charoff="50">6</td>
<td align="char" valign="top" char="." charoff="50">98</td>
<td align="char" valign="top" char="." charoff="50">1.16</td>
<td align="char" valign="top" char="." charoff="50">0.35</td>
</tr>
<tr><td align="left" valign="top" charoff="50"> </td>
<td align="char" valign="top" char="." charoff="50"> </td>
<td align="char" valign="top" char="." charoff="50"> </td>
<td align="char" valign="top" char="." charoff="50"> </td>
<td align="char" valign="top" char="." charoff="50">10</td>
<td align="char" valign="top" char="." charoff="50">11</td>
<td align="char" valign="top" char="." charoff="50">96</td>
<td align="char" valign="top" char="." charoff="50"> </td>
<td align="char" valign="top" char="." charoff="50"> </td>
</tr>
<tr><td align="left" valign="top" charoff="50"> </td>
<td align="char" valign="top" char="." charoff="50"> </td>
<td align="char" valign="top" char="." charoff="50"> </td>
<td align="char" valign="top" char="." charoff="50"> </td>
<td align="char" valign="top" char="." charoff="50">20</td>
<td align="char" valign="top" char="." charoff="50">23</td>
<td align="char" valign="top" char="." charoff="50">92</td>
<td align="char" valign="top" char="." charoff="50"> </td>
<td align="char" valign="top" char="." charoff="50"> </td>
</tr>
<tr><td align="left" valign="top" charoff="50"> </td>
<td align="char" valign="top" char="." charoff="50"> </td>
<td align="char" valign="top" char="." charoff="50"> </td>
<td align="char" valign="top" char="." charoff="50"> </td>
<td align="char" valign="top" char="." charoff="50">30</td>
<td align="char" valign="top" char="." charoff="50">33</td>
<td align="char" valign="top" char="." charoff="50">87</td>
<td align="char" valign="top" char="." charoff="50"> </td>
<td align="char" valign="top" char="." charoff="50"> </td>
</tr>
<tr><td align="left" valign="top" charoff="50"> </td>
<td align="char" valign="top" char="." charoff="50"> </td>
<td align="char" valign="top" char="." charoff="50"> </td>
<td align="char" valign="top" char="." charoff="50"> </td>
<td align="char" valign="top" char="." charoff="50">40</td>
<td align="char" valign="top" char="." charoff="50">44</td>
<td align="char" valign="top" char="." charoff="50">81</td>
<td align="char" valign="top" char="." charoff="50"> </td>
<td align="char" valign="top" char="." charoff="50"> </td>
</tr>
<tr><td align="left" valign="top" charoff="50"> </td>
<td align="char" valign="top" char="." charoff="50">0.12</td>
<td align="char" valign="top" char="." charoff="50">80</td>
<td align="char" valign="top" char="." charoff="50">70</td>
<td align="char" valign="top" char="." charoff="50">5</td>
<td align="char" valign="top" char="." charoff="50">12</td>
<td align="char" valign="top" char="." charoff="50">99</td>
<td align="char" valign="top" char="." charoff="50">2.67</td>
<td align="char" valign="top" char="." charoff="50">0.29</td>
</tr>
<tr><td align="left" valign="top" charoff="50"> </td>
<td align="char" valign="top" char="." charoff="50"> </td>
<td align="char" valign="top" char="." charoff="50"> </td>
<td align="char" valign="top" char="." charoff="50"> </td>
<td align="char" valign="top" char="." charoff="50">10</td>
<td align="char" valign="top" char="." charoff="50">23</td>
<td align="char" valign="top" char="." charoff="50">97</td>
<td align="char" valign="top" char="." charoff="50"> </td>
<td align="char" valign="top" char="." charoff="50"> </td>
</tr>
<tr><td align="left" valign="top" charoff="50"> </td>
<td align="char" valign="top" char="." charoff="50"> </td>
<td align="char" valign="top" char="." charoff="50"> </td>
<td align="char" valign="top" char="." charoff="50"> </td>
<td align="char" valign="top" char="." charoff="50">20</td>
<td align="char" valign="top" char="." charoff="50">40</td>
<td align="char" valign="top" char="." charoff="50">93</td>
<td align="char" valign="top" char="." charoff="50"> </td>
<td align="char" valign="top" char="." charoff="50"> </td>
</tr>
<tr><td align="left" valign="top" charoff="50"> </td>
<td align="char" valign="top" char="." charoff="50"> </td>
<td align="char" valign="top" char="." charoff="50"> </td>
<td align="char" valign="top" char="." charoff="50"> </td>
<td align="char" valign="top" char="." charoff="50">30</td>
<td align="char" valign="top" char="." charoff="50">53</td>
<td align="char" valign="top" char="." charoff="50">89</td>
<td align="char" valign="top" char="." charoff="50"> </td>
<td align="char" valign="top" char="." charoff="50"> </td>
</tr>
<tr><td align="left" valign="top" charoff="50"> </td>
<td align="char" valign="top" char="." charoff="50"> </td>
<td align="char" valign="top" char="." charoff="50"> </td>
<td align="char" valign="top" char="." charoff="50"> </td>
<td align="char" valign="top" char="." charoff="50">40</td>
<td align="char" valign="top" char="." charoff="50">64</td>
<td align="char" valign="top" char="." charoff="50">84</td>
<td align="char" valign="top" char="." charoff="50"> </td>
<td align="char" valign="top" char="." charoff="50"> </td>
</tr>
</tbody>
</table>
<table-wrap-foot><fn id="t4-fn1"><p>FIB-4, fibrosis 4; LR +ve, positive likelihood ratio, LR −ve, negative likelihood ratio; NFS, non-alcoholic fatty liver disease fibrosis score; NPV, negative predictive value; Prev., prevalence; PPV, positive predictive value; Sens., sensitivity; Spec., specificity.</p>
</fn>
</table-wrap-foot>
</table-wrap>
</floats-group>
</pmc>
<affiliations><list><country><li>Allemagne</li>
<li>Australie</li>
<li>Belgique</li>
<li>Brésil</li>
<li>Espagne</li>
<li>France</li>
<li>Italie</li>
<li>Royaume-Uni</li>
<li>Suisse</li>
</country>
</list>
<tree><country name="Royaume-Uni"><noRegion><name sortKey="Mcpherson, Stuart" sort="Mcpherson, Stuart" uniqKey="Mcpherson S" first="Stuart" last="Mcpherson">Stuart Mcpherson</name>
</noRegion>
<name sortKey="Allison, Mike" sort="Allison, Mike" uniqKey="Allison M" first="Mike" last="Allison">Mike Allison</name>
<name sortKey="Anstee, Quentin M" sort="Anstee, Quentin M" uniqKey="Anstee Q" first="Quentin M" last="Anstee">Quentin M. Anstee</name>
<name sortKey="Anstee, Quentin M" sort="Anstee, Quentin M" uniqKey="Anstee Q" first="Quentin M" last="Anstee">Quentin M. Anstee</name>
<name sortKey="Day, Christopher P" sort="Day, Christopher P" uniqKey="Day C" first="Christopher P" last="Day">Christopher P. Day</name>
<name sortKey="Day, Christopher P" sort="Day, Christopher P" uniqKey="Day C" first="Christopher P" last="Day">Christopher P. Day</name>
<name sortKey="Hardy, Tim" sort="Hardy, Tim" uniqKey="Hardy T" first="Tim" last="Hardy">Tim Hardy</name>
<name sortKey="Hardy, Tim" sort="Hardy, Tim" uniqKey="Hardy T" first="Tim" last="Hardy">Tim Hardy</name>
<name sortKey="Mcpherson, Stuart" sort="Mcpherson, Stuart" uniqKey="Mcpherson S" first="Stuart" last="Mcpherson">Stuart Mcpherson</name>
<name sortKey="Tiniakos, Dina" sort="Tiniakos, Dina" uniqKey="Tiniakos D" first="Dina" last="Tiniakos">Dina Tiniakos</name>
<name sortKey="Tiniakos, Dina" sort="Tiniakos, Dina" uniqKey="Tiniakos D" first="Dina" last="Tiniakos">Dina Tiniakos</name>
</country>
<country name="Suisse"><noRegion><name sortKey="Dufour, Jean Francois" sort="Dufour, Jean Francois" uniqKey="Dufour J" first="Jean-Francois" last="Dufour">Jean-Francois Dufour</name>
</noRegion>
</country>
<country name="Italie"><noRegion><name sortKey="Petta, Salvatore" sort="Petta, Salvatore" uniqKey="Petta S" first="Salvatore" last="Petta">Salvatore Petta</name>
</noRegion>
<name sortKey="Bugianesi, Elisabetta" sort="Bugianesi, Elisabetta" uniqKey="Bugianesi E" first="Elisabetta" last="Bugianesi">Elisabetta Bugianesi</name>
</country>
<country name="Espagne"><noRegion><name sortKey="Romero Gomez, Manuel" sort="Romero Gomez, Manuel" uniqKey="Romero Gomez M" first="Manuel" last="Romero-Gomez">Manuel Romero-Gomez</name>
</noRegion>
</country>
<country name="Brésil"><noRegion><name sortKey="Oliveira, Claudia P" sort="Oliveira, Claudia P" uniqKey="Oliveira C" first="Claudia P" last="Oliveira">Claudia P. Oliveira</name>
</noRegion>
</country>
<country name="Belgique"><noRegion><name sortKey="Francque, Sven" sort="Francque, Sven" uniqKey="Francque S" first="Sven" last="Francque">Sven Francque</name>
</noRegion>
<name sortKey="Van Gaal, Luc" sort="Van Gaal, Luc" uniqKey="Van Gaal L" first="Luc" last="Van Gaal">Luc Van Gaal</name>
</country>
<country name="Allemagne"><noRegion><name sortKey="Schattenberg, Jorn M" sort="Schattenberg, Jorn M" uniqKey="Schattenberg J" first="Jörn M" last="Schattenberg">Jörn M. Schattenberg</name>
</noRegion>
</country>
<country name="Australie"><noRegion><name sortKey="Burt, Alastair" sort="Burt, Alastair" uniqKey="Burt A" first="Alastair" last="Burt">Alastair Burt</name>
</noRegion>
</country>
<country name="France"><noRegion><name sortKey="Ratziu, Vlad" sort="Ratziu, Vlad" uniqKey="Ratziu V" first="Vlad" last="Ratziu">Vlad Ratziu</name>
</noRegion>
</country>
</tree>
</affiliations>
</record>
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