{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T17:42:15Z","timestamp":1788975735419,"version":"build-2803163510"},"reference-count":21,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2023,9,4]],"date-time":"2023-09-04T00:00:00Z","timestamp":1693785600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Histopathology"],"published-print":{"date-parts":[[2023,12]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>Wilson disease (WD) is a genetic disorder of copper metabolism caused by mutations in the <jats:italic>ATP7B<\/jats:italic> gene. Toxic copper accumulation leads to hepatic, neurologic, and psychiatric disorders with variable presentation. Metallothionein (MT) immunohistochemistry was proposed as a diagnostic marker.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>MT immunohistochemistry was performed on liver specimens of WD patients (<jats:italic>n<\/jats:italic>\u2009=\u200964) and control cases (<jats:italic>n<\/jats:italic>\u2009=\u2009160) including acute liver failure, steatotic liver disease, autoimmune hepatitis, normal liver, primary biliary cholangitis, primary and secondary sclerosing cholangitis, and progressive familial intrahepatic cholestasis. The optimal cutoff for detection of WD was determined by receiver operating characteristic (ROC) analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>At least moderate staining in &gt;50% of hepatocytes was observed in 81% of analysed liver specimens (<jats:italic>n<\/jats:italic>\u2009=\u200956\/69) of WD patients, while only five control cases showed this staining pattern. The sensitivity, specificity, and accuracy for a new diagnosis of WD were 85.7%, 96.9%, and 94.9%, respectively. Sensitivity in nonfibrotic patients was 70.6% and this MT pattern was robust in small biopsies. The\u00a0hepatic copper concentration was similar between MT\u2010positive and MT\u2010negative liver samples (<jats:italic>P<\/jats:italic>\u2009&gt;\u20090.05). Zinc treatment may induce hepatocellular MT expression. Kayser\u2013Fleischer rings (50% versus 15%) and neurologic disorders (50% versus 13%) were significantly more prevalent in MT\u2010negative compared to MT\u2010positive WD patients, respectively.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>MT immunostaining is an excellent biomarker for histological diagnosis of WD, should be incorporated in the diagnostic work\u2010up of patients with potential WD, and is useful in a modified Leipzig score.<\/jats:p><\/jats:sec>","DOI":"10.1111\/his.15041","type":"journal-article","created":{"date-parts":[[2023,9,4]],"date-time":"2023-09-04T07:22:46Z","timestamp":1693812166000},"page":"936-948","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Metallothionein: a game changer in histopathological diagnosis of Wilson disease"],"prefix":"10.1111","volume":"83","author":[{"given":"Hendrik","family":"Wiethoff","sequence":"first","affiliation":[{"name":"Institute of Pathology, Heidelberg University Hospital  Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabelle","family":"Mohr","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Infectious Diseases and Intoxication, Internal Medicine IV Heidelberg University Hospital  Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Fichtner","sequence":"additional","affiliation":[{"name":"Department of Pediatrics I University Children's Hospital Heidelberg  Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uta","family":"Merle","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Infectious Diseases and Intoxication, Internal Medicine IV Heidelberg University Hospital  Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Schirmacher","sequence":"additional","affiliation":[{"name":"Institute of Pathology, Heidelberg University Hospital  Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karl H","family":"Weiss","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Salem Medical Center  Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8888-1030","authenticated-orcid":false,"given":"Thomas","family":"Longerich","sequence":"additional","affiliation":[{"name":"Institute of Pathology, Heidelberg University Hospital  Heidelberg 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