{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T17:13:56Z","timestamp":1790097236013,"version":"4.0.1"},"reference-count":35,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2022,6,6]],"date-time":"2022-06-06T00:00:00Z","timestamp":1654473600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2022,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background and Aims<\/jats:title>\n                    <jats:p>Wilson disease (WD) has diverse presentations that frequently mimic other liver diseases. Distinguishing WD from non\u2010alcoholic fatty liver disease (NAFLD) and autoimmune hepatitis (AIH), can be difficult and has critical implications for medical management. This study aimed to examine the utility of histological features of WD in children compared to those with NAFLD and AIH.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A review of liver biopsy slides was performed in children with a clinical and\/or genetic diagnosis of WD, seen at the Hospital for Sick Children between 1981 and 2019 and compared to controls with NAFLD and AIH. 37 children with WD and 37 disease controls (20 NAFLD; 17 AIH) were included. Three pathologists, blind to clinical details and diagnosis, reviewed all liver biopsies to reach consensus. Clinical and histopathologic features were compared between groups.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Most WD cases displayed steatosis or steatohepatitis on histology (34\/37), active AIH\u2010pattern in 1 and inactive cirrhosis in 2 cases. Electron microscopy (EM) findings of mitochondrial abnormalities including dilated tips of cristae, pleomorphism, membrane duplication and dense matrix were more frequent in the WD group as compared to disease controls (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.0001). In WD, dilated tips of mitochondrial cristae had a sensitivity of 91% and specificity of 86%, best among EM features.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Light microscopic findings display considerable overlap among children with WD, NAFLD and AIH. Ultrastructural findings of mitochondrial abnormalities are important to distinguish WD from NAFLD and AIH. EM examination should be considered essential in the diagnostic work\u2010up of paediatric liver biopsies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/liv.15319","type":"journal-article","created":{"date-parts":[[2022,5,23]],"date-time":"2022-05-23T03:50:43Z","timestamp":1653277843000},"page":"2482-2491","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Hepatic ultrastructural features distinguish paediatric Wilson disease from\n                    <scp>NAFLD<\/scp>\n                    and autoimmune hepatitis"],"prefix":"10.1111","volume":"42","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7569-1238","authenticated-orcid":false,"given":"Saleh A.","family":"Alqahtani","sequence":"first","affiliation":[{"name":"Department of Pediatrics Imam Abdulrahman Bin Faisal University  Dammam Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1242-9352","authenticated-orcid":false,"given":"Rose","family":"Chami","sequence":"additional","affiliation":[{"name":"Department of Pathology Hospital for Sick Children, University of Toronto  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7269-7853","authenticated-orcid":false,"given":"Dua","family":"Abuquteish","sequence":"additional","affiliation":[{"name":"Department of Basic Medical Sciences, Faculty of Medicine The Hashemite University  Zarqa Jordan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7157-2063","authenticated-orcid":false,"given":"Shannon M.","family":"Vandriel","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Hepatology and Nutrition Hospital for Sick Children, University of Toronto  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charesse","family":"Yap","sequence":"additional","affiliation":[{"name":"Department of Pathology Hospital for Sick Children, University of Toronto  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0963-7924","authenticated-orcid":false,"given":"Liyana","family":"Kukkadi","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Hepatology and Nutrition Hospital for Sick Children, University of Toronto  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aishwarya","family":"Parmar","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Hepatology and Nutrition Hospital for Sick Children, University of Toronto  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amrita","family":"Mundh","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Hepatology and Nutrition Hospital for Sick Children, University of Toronto  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eve A.","family":"Roberts","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Hepatology and Nutrition Hospital for Sick Children, University of Toronto  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Binita M.","family":"Kamath","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Hepatology and Nutrition Hospital for Sick Children, University of Toronto  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iram","family":"Siddiqui","sequence":"additional","affiliation":[{"name":"Department of Pathology Hospital for Sick Children, University of Toronto  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,6,6]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1293-327"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-444-63625-6.00003-3"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1039\/c2mt20019h"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1039\/b711118p"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1136\/gut.2005.087262"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.30280"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.23910"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1097\/MPG.0000000000002007"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1097\/MPG.0000000000002777"},{"key":"e_1_2_12_11_1","first-page":"257","volume-title":"Clinical and Translational Perspectives on Wilson Disease","author":"Lackner C","year":"2018"},{"key":"e_1_2_12_12_1","first-page":"315","article-title":"Hepatocellular changes in Wilson's disease. 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