Serum Matrix Metalloproteinase 7 Is a Diagnostic Biomarker of Biliary Injury and Fibrosis in Pediatric Autoimmune Liver Disease
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 scler...
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| Veröffentlicht in: | Hepatology communications 2020-11, Vol.4 (11), p.1680-1693 |
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| creator | Lam, Simon Singh, Ruchi Dillman, Jonathan R. Trout, Andrew T. Serai, Suraj D. Sharma, Divya Sheridan, Rachel Su, Weizhe Fei, Lin Karns, Rebekah Haramija, Marija M. Ridgway, Ged Goldfinger, Marc Squires, James E. Denson, Lee A. Hyams, Jeffery S. Miethke, Alexander G. |
| description | 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 years) with AILD (AIH, n = 26; ASC, n = 16; and PSC, n = 12) at our center. The sMMP7 concentrations were higher in patients with SC compared to those without cholangiopathy (P 23.7 ng/mL had a sensitivity and specificity of 79% and 96%, respectively, and outperformed alkaline phosphatase (ALP) and gamma‐glutamyltransferase (GGT) in segregating patients with SC. Serum concentrations correlated with liver gene expression levels for MMP7 (r = 0.70; P |
| doi_str_mv | 10.1002/hep4.1589 |
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We studied serum matrix metalloproteinase 7 (sMMP7) as a biomarker for pediatric sclerosing cholangitis (SC). We prospectively enrolled 54 children (median age, 16 years) with AILD (AIH, n = 26; ASC, n = 16; and PSC, n = 12) at our center. The sMMP7 concentrations were higher in patients with SC compared to those without cholangiopathy (P < 0.001). An sMMP7 concentration >23.7 ng/mL had a sensitivity and specificity of 79% and 96%, respectively, and outperformed alkaline phosphatase (ALP) and gamma‐glutamyltransferase (GGT) in segregating patients with SC. Serum concentrations correlated with liver gene expression levels for MMP7 (r = 0.70; P < 0.001). 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 (r = 0.56; P < 0.01). Using magnetic resonance cholangiopancreatography plus (MRCP+), sMMP7 in 34 patients correlated with the number of biliary dilatations (r = 0.54; P < 0.01) and strictures (r = 0.56; P < 0.01). 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‐related complication. Conclusion: 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.</description><identifier>ISSN: 2471-254X</identifier><identifier>EISSN: 2471-254X</identifier><identifier>DOI: 10.1002/hep4.1589</identifier><identifier>PMID: 33163837</identifier><language>eng</language><publisher>United States: Wolters Kluwer Health Medical Research, Lippincott Williams & Wilkins</publisher><subject>Bile ; Biomarkers ; Inflammatory bowel disease ; Magnetic resonance imaging ; Original</subject><ispartof>Hepatology communications, 2020-11, Vol.4 (11), p.1680-1693</ispartof><rights>2020 The Authors. Hepatology Communications published by Wiley Periodicals LLC on behalf of the American Association for the Study of Liver Diseases.</rights><rights>2020. This work is published under http://creativecommons.org/licenses/by-nc-nd/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5099-422403409c8e955aab4a9cbea4852977b159f10ee27d745796f0fb55cfe8b1093</citedby><cites>FETCH-LOGICAL-c5099-422403409c8e955aab4a9cbea4852977b159f10ee27d745796f0fb55cfe8b1093</cites><orcidid>0000-0002-0540-1466</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7603534/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7603534/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,315,728,781,785,865,886,1418,2103,11564,27926,27927,45576,45577,46054,46478,53793,53795</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33163837$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lam, Simon</creatorcontrib><creatorcontrib>Singh, Ruchi</creatorcontrib><creatorcontrib>Dillman, Jonathan R.</creatorcontrib><creatorcontrib>Trout, Andrew T.</creatorcontrib><creatorcontrib>Serai, Suraj D.</creatorcontrib><creatorcontrib>Sharma, Divya</creatorcontrib><creatorcontrib>Sheridan, Rachel</creatorcontrib><creatorcontrib>Su, Weizhe</creatorcontrib><creatorcontrib>Fei, Lin</creatorcontrib><creatorcontrib>Karns, Rebekah</creatorcontrib><creatorcontrib>Haramija, Marija M.</creatorcontrib><creatorcontrib>Ridgway, Ged</creatorcontrib><creatorcontrib>Goldfinger, Marc</creatorcontrib><creatorcontrib>Squires, James E.</creatorcontrib><creatorcontrib>Denson, Lee A.</creatorcontrib><creatorcontrib>Hyams, Jeffery S.</creatorcontrib><creatorcontrib>Miethke, Alexander G.</creatorcontrib><title>Serum Matrix Metalloproteinase 7 Is a Diagnostic Biomarker of Biliary Injury and Fibrosis in Pediatric Autoimmune Liver Disease</title><title>Hepatology communications</title><addtitle>Hepatol Commun</addtitle><description>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 years) with AILD (AIH, n = 26; ASC, n = 16; and PSC, n = 12) at our center. The sMMP7 concentrations were higher in patients with SC compared to those without cholangiopathy (P < 0.001). An sMMP7 concentration >23.7 ng/mL had a sensitivity and specificity of 79% and 96%, respectively, and outperformed alkaline phosphatase (ALP) and gamma‐glutamyltransferase (GGT) in segregating patients with SC. Serum concentrations correlated with liver gene expression levels for MMP7 (r = 0.70; P < 0.001). 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 (r = 0.56; P < 0.01). Using magnetic resonance cholangiopancreatography plus (MRCP+), sMMP7 in 34 patients correlated with the number of biliary dilatations (r = 0.54; P < 0.01) and strictures (r = 0.56; P < 0.01). 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‐related complication. 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Singh, Ruchi ; Dillman, Jonathan R. ; Trout, Andrew T. ; Serai, Suraj D. ; Sharma, Divya ; Sheridan, Rachel ; Su, Weizhe ; Fei, Lin ; Karns, Rebekah ; Haramija, Marija M. ; Ridgway, Ged ; Goldfinger, Marc ; Squires, James E. ; Denson, Lee A. ; Hyams, Jeffery S. ; Miethke, Alexander G.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5099-422403409c8e955aab4a9cbea4852977b159f10ee27d745796f0fb55cfe8b1093</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Bile</topic><topic>Biomarkers</topic><topic>Inflammatory bowel disease</topic><topic>Magnetic resonance imaging</topic><topic>Original</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lam, Simon</creatorcontrib><creatorcontrib>Singh, Ruchi</creatorcontrib><creatorcontrib>Dillman, Jonathan R.</creatorcontrib><creatorcontrib>Trout, Andrew T.</creatorcontrib><creatorcontrib>Serai, Suraj D.</creatorcontrib><creatorcontrib>Sharma, Divya</creatorcontrib><creatorcontrib>Sheridan, Rachel</creatorcontrib><creatorcontrib>Su, Weizhe</creatorcontrib><creatorcontrib>Fei, Lin</creatorcontrib><creatorcontrib>Karns, Rebekah</creatorcontrib><creatorcontrib>Haramija, Marija M.</creatorcontrib><creatorcontrib>Ridgway, Ged</creatorcontrib><creatorcontrib>Goldfinger, Marc</creatorcontrib><creatorcontrib>Squires, James E.</creatorcontrib><creatorcontrib>Denson, Lee A.</creatorcontrib><creatorcontrib>Hyams, Jeffery S.</creatorcontrib><creatorcontrib>Miethke, Alexander G.</creatorcontrib><collection>Open Access: Wiley-Blackwell Open Access Journals</collection><collection>Wiley Online Library</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection (Proquest)</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>AUTh Library subscriptions: ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>Directory of Open Access Journals</collection><jtitle>Hepatology communications</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lam, Simon</au><au>Singh, Ruchi</au><au>Dillman, Jonathan R.</au><au>Trout, Andrew T.</au><au>Serai, Suraj D.</au><au>Sharma, Divya</au><au>Sheridan, Rachel</au><au>Su, Weizhe</au><au>Fei, Lin</au><au>Karns, Rebekah</au><au>Haramija, Marija M.</au><au>Ridgway, Ged</au><au>Goldfinger, Marc</au><au>Squires, James E.</au><au>Denson, Lee A.</au><au>Hyams, Jeffery S.</au><au>Miethke, Alexander G.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Serum Matrix Metalloproteinase 7 Is a Diagnostic Biomarker of Biliary Injury and Fibrosis in Pediatric Autoimmune Liver Disease</atitle><jtitle>Hepatology communications</jtitle><addtitle>Hepatol Commun</addtitle><date>2020-11</date><risdate>2020</risdate><volume>4</volume><issue>11</issue><spage>1680</spage><epage>1693</epage><pages>1680-1693</pages><issn>2471-254X</issn><eissn>2471-254X</eissn><abstract>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 years) with AILD (AIH, n = 26; ASC, n = 16; and PSC, n = 12) at our center. The sMMP7 concentrations were higher in patients with SC compared to those without cholangiopathy (P < 0.001). An sMMP7 concentration >23.7 ng/mL had a sensitivity and specificity of 79% and 96%, respectively, and outperformed alkaline phosphatase (ALP) and gamma‐glutamyltransferase (GGT) in segregating patients with SC. Serum concentrations correlated with liver gene expression levels for MMP7 (r = 0.70; P < 0.001). 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 (r = 0.56; P < 0.01). Using magnetic resonance cholangiopancreatography plus (MRCP+), sMMP7 in 34 patients correlated with the number of biliary dilatations (r = 0.54; P < 0.01) and strictures (r = 0.56; P < 0.01). 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‐related complication. Conclusion: 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.</abstract><cop>United States</cop><pub>Wolters Kluwer Health Medical Research, Lippincott Williams & Wilkins</pub><pmid>33163837</pmid><doi>10.1002/hep4.1589</doi><tpages>14</tpages><orcidid>https://orcid.org/0000-0002-0540-1466</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Bile Biomarkers Inflammatory bowel disease Magnetic resonance imaging Original |
| title | Serum Matrix Metalloproteinase 7 Is a Diagnostic Biomarker of Biliary Injury and Fibrosis in Pediatric Autoimmune Liver Disease |
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