{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T12:04:09Z","timestamp":1789128249114,"version":"build-2803163510"},"reference-count":37,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"11","license":[{"start":{"date-parts":[[2020,9,24]],"date-time":"2020-09-24T00:00:00Z","timestamp":1600905600000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Hepatol. Commun."],"published-print":{"date-parts":[[2020,11]]},"abstract":"<jats:p>In autoimmune liver disease (AILD), including autoimmune hepatitis (AIH), primary sclerosing cholangitis (PSC), and overlap syndrome of AIH and PSC (ASC), the presence of biliary injury portends a worse prognosis. We studied serum matrix metalloproteinase 7 (sMMP7) as a biomarker for pediatric sclerosing cholangitis (SC). We prospectively enrolled 54 children (median age, 16\u00a0years) with AILD (AIH, n\u00a0=\u00a026; ASC,\u00a0n =\u00a016; and PSC, n\u00a0=\u00a012) at our center. The sMMP7 concentrations were higher in patients with SC compared to those without cholangiopathy (<jats:italic toggle=\"yes\">P<\/jats:italic>\u00a0&lt;\u00a00.001). An sMMP7 concentration &gt;23.7\u00a0ng\/mL had a sensitivity and specificity of 79% and 96%, respectively, and outperformed alkaline phosphatase (ALP) and gamma\u2010glutamyltransferase (GGT) in segregating patients with SC. Serum concentrations correlated with liver gene expression levels for <jats:italic toggle=\"yes\">MMP7<\/jats:italic> (<jats:italic toggle=\"yes\">r<\/jats:italic>\u00a0=\u00a00.70; <jats:italic toggle=\"yes\">P<\/jats:italic>\u00a0&lt;\u00a00.001). Using immunofluorescence, MMP7 was localized primarily to the cholangiocytes of patients with SC. In 46 subjects with liver biopsy available for blinded review, elevation in sMMP7 concentrations segregated with the presence of lymphocytic and neutrophilic cholangitis and periductal fibrosis and correlated with Ishak, Ludwig, and Nakanuma scoring systems. Liver stiffness measured by magnetic resonance elastography also correlated with sMMP7 concentrations (<jats:italic toggle=\"yes\">r<\/jats:italic>\u00a0=\u00a00.56; <jats:italic toggle=\"yes\">P<\/jats:italic>\u00a0&lt;\u00a00.01). Using magnetic resonance cholangiopancreatography plus (MRCP+), sMMP7 in 34 patients correlated with the number of biliary dilatations (<jats:italic toggle=\"yes\">r<\/jats:italic>\u00a0=\u00a00.54; <jats:italic toggle=\"yes\">P<\/jats:italic>\u00a0&lt;\u00a00.01) and strictures (<jats:italic toggle=\"yes\">r<\/jats:italic>\u00a0=\u00a00.56; <jats:italic toggle=\"yes\">P<\/jats:italic>\u00a0&lt;\u00a00.01). MMP7 as a marker of biliary injury was validated in an independent cohort of children with ulcerative colitis. Higher sMMP7 concentrations also correlated with a history of SC\u2010related complication. <jats:italic toggle=\"yes\">Conclusion<\/jats:italic>: MMP7 is a promising biomarker for pediatric SC that diagnostically outperforms ALP and GGT. sMMP7 may directly reflect biliary injury and fibrosis, the main drivers of disease progression in SC.<\/jats:p>","DOI":"10.1002\/hep4.1589","type":"journal-article","created":{"date-parts":[[2020,9,24]],"date-time":"2020-09-24T11:57:13Z","timestamp":1600948633000},"page":"1680-1693","source":"Crossref","is-referenced-by-count":27,"title":["Serum Matrix Metalloproteinase 7 Is a Diagnostic Biomarker of Biliary Injury and Fibrosis in Pediatric Autoimmune Liver Disease"],"prefix":"10.1097","volume":"4","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0540-1466","authenticated-orcid":false,"given":"Simon","family":"Lam","sequence":"first","affiliation":[{"name":"Division of Gastroenterology, Hepatology and Nutrition,Cincinnati Children's Hospital Medical Center,Cincinnati,OH,USA"},{"name":"Department of Pediatrics,University of Cincinnati College of Medicine,Cincinnati,OH,USA"},{"name":"Section of Pediatric Gastroenterology,Department of Pediatrics,Alberta Children\u2019s Hospital,University of Calgary,Calgary,Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruchi","family":"Singh","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Hepatology and Nutrition,Cincinnati Children's Hospital Medical Center,Cincinnati,OH,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan R.","family":"Dillman","sequence":"additional","affiliation":[{"name":"Department of Pediatrics,University of Cincinnati College of Medicine,Cincinnati,OH,USA"},{"name":"Department of Radiology,Cincinnati Children's Hospital Medical Center,University of Cincinnati College of Medicine,Cincinnati,OH,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew T.","family":"Trout","sequence":"additional","affiliation":[{"name":"Department of Pediatrics,University of Cincinnati College of Medicine,Cincinnati,OH,USA"},{"name":"Department of Radiology,Cincinnati Children's Hospital Medical Center,University of Cincinnati College of Medicine,Cincinnati,OH,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suraj D.","family":"Serai","sequence":"additional","affiliation":[{"name":"Department of Radiology,Children\u2019s Hospital of Philadelphia,Philadelphia,PA,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Divya","family":"Sharma","sequence":"additional","affiliation":[{"name":"Division of Pathology,University of Cincinnati,Cincinnati,OH,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel","family":"Sheridan","sequence":"additional","affiliation":[{"name":"Department of Pathology,Dayton Children\u2019s Hospital,Dayton,OH,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weizhe","family":"Su","sequence":"additional","affiliation":[{"name":"Division of Biostatistics and Epidemiology,Cincinnati Children's Hospital Medical Center,Cincinnati,OH,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Fei","sequence":"additional","affiliation":[{"name":"Division of Biostatistics and Epidemiology,Cincinnati Children's Hospital Medical Center,Cincinnati,OH,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebekah","family":"Karns","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Hepatology and Nutrition,Cincinnati Children's Hospital Medical Center,Cincinnati,OH,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marija M.","family":"Haramija","sequence":"additional","affiliation":[{"name":"Perspectum Diagnostics Ltd.,South San Francisco,CA,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ged","family":"Ridgway","sequence":"additional","affiliation":[{"name":"Perspectum Diagnostics Ltd.,South San Francisco,CA,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"Goldfinger","sequence":"additional","affiliation":[{"name":"Perspectum Diagnostics Ltd.,South San Francisco,CA,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James E.","family":"Squires","sequence":"additional","affiliation":[{"name":"Children\u2019s Hospital of Pittsburgh,Pittsburgh,PA,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lee A.","family":"Denson","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Hepatology and Nutrition,Cincinnati Children's Hospital Medical Center,Cincinnati,OH,USA"},{"name":"Department of Pediatrics,University of Cincinnati College of Medicine,Cincinnati,OH,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffery S.","family":"Hyams","sequence":"additional","affiliation":[{"name":"Division of Digestive Diseases,Hepatology, and Nutrition,Connecticut Children\u2019s Hospital Medical Center,Hartford,CT,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander G.","family":"Miethke","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Hepatology and Nutrition,Cincinnati Children's Hospital Medical Center,Cincinnati,OH,USA"},{"name":"Department of Pediatrics,University of Cincinnati College of Medicine,Cincinnati,OH,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2020,9,24]]},"reference":[{"key":"hep41589-bib-0001-20240114","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1016\/j.bpg.2011.10.007","article-title":"Autoimmune liver diseases in children\u2014what is different from 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