{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T00:05:42Z","timestamp":1791504342103,"version":"4.3.4"},"reference-count":15,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":1460,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2011,9,2]]},"abstract":"<jats:sec>\n            <jats:title\/>\n            <jats:p>\n                                 <jats:bold>Distinguishing drug-induced liver injury (DILI) from idiopathic autoimmune hepatitis (AIH) can be challenging. We performed a standardized histologic evaluation to explore potential hallmarks to differentiate AIH versus DILI. Biopsies from patients with clinically well-characterized DILI [n = 35, including 19 hepatocellular injury (HC) and 16 cholestatic\/mixed injury (CS)] and AIH (n = 28) were evaluated for Ishak scores, prominent inflammatory cell types in portal and intra-acinar areas, the presence or absence of emperipolesis, rosette formation, and cholestasis in a blinded fashion by four experienced hepatopathologists. Histologic diagnosis was concordant with clinical diagnosis in 65% of cases; but agreement on final diagnosis among the four pathologists was complete in only 46% of cases. Interface hepatitis, focal necrosis, and portal inflammation were present in all evaluated cases, but were more severe in AIH<\/jats:bold>\n                                 <jats:bold>\n                                    (P\n                                 <\/jats:bold>\n                                 <jats:bold>&lt; 0.05) than DILI (HC). Portal and intra-acinar plasma cells, rosette formation, and emperiopolesis were features that favored AIH<\/jats:bold>\n                                 <jats:bold>\n                                    (P\n                                 <\/jats:bold>\n                                 <jats:bold>&lt; 0.02). A model combining portal inflammation, portal plasma cells, intra-acinar lymphocytes and eosinophils, rosette formation, and canalicular cholestasis yielded an area under the receiver operating characteristic curve (AUROC) of 0.90 in predicting DILI (HC) versus AIH. All Ishak inflammation scores were more severe in AIH than DILI (CS)<\/jats:bold>\n                                 <jats:bold>\n                                    (P\n                                 <\/jats:bold>\n                                 <jats:bold>\u2264 0.05). The four AIH-favoring features listed above were consistently more prevalent in AIH, whereas portal neutrophils and intracellular (hepatocellular) cholestasis were more prevalent in DILI (CS)<\/jats:bold>\n                                 <jats:bold>\n                                    (P\n                                 <\/jats:bold>\n                                 <jats:bold>&lt; 0.02). The combination of portal inflammation, fibrosis, portal neutrophils and plasma cells, and intracellular (hepatocellular) cholestasis yielded an AUC of 0.91 in predicting DILI (CS) versus AIH.<\/jats:bold>\n                                 <jats:bold>\n                                    Conclusion:\n                                 <\/jats:bold>\n                                 <jats:bold>Although an overlap of histologic findings exists for AIH and DILI, sufficient differences exist so that pathologists can use the pattern of injury to suggest the correct diagnosis. (Hepatology 2011;)<\/jats:bold>\n                              <\/jats:p>\n          <\/jats:sec>","DOI":"10.1002\/hep.24481","type":"journal-article","created":{"date-parts":[[2011,6,14]],"date-time":"2011-06-14T14:59:48Z","timestamp":1308063588000},"page":"931-939","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":308,"title":["The use of liver biopsy evaluation in discrimination of idiopathic autoimmune hepatitis versus drug-induced liver injury"],"prefix":"10.1097","volume":"54","author":[{"given":"Ayako","family":"Suzuki","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth M.","family":"Brunt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David E.","family":"Kleiner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosa","family":"Miquel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas C.","family":"Smyrk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raul J.","family":"Andrade","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabel M.","family":"Lucena","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agustin","family":"Castiella","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keith","family":"Lindor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Einar","family":"Bj\u00f6rnsson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"R1-21-20241201","doi-asserted-by":"crossref","first-page":"20402048","DOI":"10.1002\/hep.23588","article-title":"Druginduced autoimmune hepatitis: clinical characteristics and prognosis.","volume":"51","author":"Bjornsson","year":"2010","journal-title":"HEPATOLOGY"},{"key":"R2-21-20241201","doi-asserted-by":"crossref","first-page":"755774","DOI":"10.1016\/S1089-3261(02)00025-9","article-title":"Immunemediated druginduced liver disease.","volume":"6","author":"Liu","year":"2002","journal-title":"Clin Liver Dis"},{"key":"R3-21-20241201","doi-asserted-by":"crossref","first-page":"383392","DOI":"10.1055\/s-0029-1240007","article-title":"Immunoallergic druginduced liver injury in humans.","volume":"29","author":"Uetrecht","year":"2009","journal-title":"Semin Liver Dis"},{"key":"R4-21-20241201","doi-asserted-by":"crossref","first-page":"277294","DOI":"10.2165\/00002018-200730040-00001","article-title":"Druginduced liver injury.","volume":"30","author":"Abboud","year":"2007","journal-title":"Drug Saf"},{"key":"R5-21-20241201","doi-asserted-by":"crossref","first-page":"7883","DOI":"10.1136\/gut.21.1.78","article-title":"Late results of the Royal Free Hospital prospective controlled trial of prednisolone therapy in hepatitis B surface antigen negative chronic active hepatitis.","volume":"21","author":"Kirk","year":"1980","journal-title":"Gut"},{"key":"R6-21-20241201","doi-asserted-by":"crossref","first-page":"253256","DOI":"10.1097\/00007890-199907270-00016","article-title":"Recurrence of autoimmune hepatitis after liver transplantation.","volume":"68","author":"Milkiewicz","year":"1999","journal-title":"Transplantation"},{"key":"R7-21-20241201","doi-asserted-by":"crossref","first-page":"820833","DOI":"10.1016\/S0016-5085(19)33223-8","article-title":"Clinical, biochemical, and histological remission of severe chronic active liver disease: a controlled study of treatments and early prognosis.","volume":"63","author":"Soloway","year":"1972","journal-title":"Gastroenterology"},{"key":"R8-21-20241201","doi-asserted-by":"crossref","first-page":"364372","DOI":"10.1055\/s-0029-1240005","article-title":"The pathology of druginduced liver injury.","volume":"29","author":"Kleiner","year":"2009","journal-title":"Semin Liver Dis"},{"key":"R10-21-20241201","doi-asserted-by":"crossref","first-page":"349362","DOI":"10.1016\/S1089-3261(02)00007-7","article-title":"Autoimmune hepatitis and overlap syndromes.","volume":"6","author":"Dienes","year":"2002","journal-title":"Clin Liver Dis"},{"key":"R11-21-20241201","doi-asserted-by":"crossref","first-page":"169176","DOI":"10.1002\/hep.22322","article-title":"Simplified criteria for the diagnosis of autoimmune hepatitis.","volume":"48","author":"Hennes","year":"2008","journal-title":"HEPATOLOGY"},{"key":"R12-21-20241201","first-page":"272276","article-title":"Criteria of druginduced liver disorders. 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