{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T12:33:38Z","timestamp":1791894818098,"version":"4.3.4"},"reference-count":16,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","license":[{"start":{"date-parts":[[2013,12,18]],"date-time":"2013-12-18T00:00:00Z","timestamp":1387324800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/3.0\/"},{"start":{"date-parts":[[2014,2,1]],"date-time":"2014-02-01T00:00:00Z","timestamp":1391212800000},"content-version":"tdm","delay-in-days":0,"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":[[2014,2]]},"abstract":"<jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      <jats:bold>Drug-induced liver injury (DILI) is considered to be a diagnosis of exclusion. Liver biopsy may contribute to diagnostic accuracy, but the histological features of DILI and their relationship to biochemical parameters and outcomes are not well defined. We have classified the pathological pattern of liver injury and systematically evaluated histological changes in liver biopsies obtained from 249 patients with suspected DILI enrolled in the prospective, observational study conducted by the Drug Induced Liver Injury Network. Histological features were analyzed for their frequency within different clinical phenotypes of liver injury and to identify associations between clinical and laboratory findings and histological features. The most common histological patterns were acute (21%) and chronic hepatitis (14%), acute (9%) and chronic cholestasis (10%), and cholestatic hepatitis (29%). Liver histology from 128 patients presenting with hepatocellular injury had more severe inflammation, necrosis, and apoptosis and more frequently demonstrated lobular disarray, rosette formation, and hemorrhage than those with cholestasis. Conversely, histology of the 73 patients with cholestatic injury more often demonstrated bile plugs and duct paucity. Severe or fatal hepatic injury in 46 patients was associated with higher degrees of necrosis, fibrosis stage, microvesicular steatosis, and ductular reaction among other findings, whereas eosinophils and granulomas were found more often in those with milder injury.<\/jats:bold>\n                      <jats:bold>Conclusion<\/jats:bold>\n                      <jats:bold>: We describe an approach for evaluating liver histology in DILI and demonstrate numerous associations between pathological findings and clinical presentations that may serve as a foundation for future studies correlating DILI pathology with its causality and outcome. (Hepatology 2014;59:661\u2013670)<\/jats:bold>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/hep.26709","type":"journal-article","created":{"date-parts":[[2013,8,28]],"date-time":"2013-08-28T12:06:35Z","timestamp":1377691595000},"page":"661-670","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":394,"title":["Hepatic Histological Findings in Suspected Drug-Induced Liver Injury: Systematic Evaluation and Clinical Associations"],"prefix":"10.1097","volume":"59","author":[{"given":"David E.","family":"Kleiner","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naga P.","family":"Chalasani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William M.","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert J.","family":"Fontana","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Herbert L.","family":"Bonkovsky","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul B.","family":"Watkins","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul H.","family":"Hayashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy J.","family":"Davern","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor","family":"Navarro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajender","family":"Reddy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jayant A.","family":"Talwalkar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Stolz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiezhun","family":"Gu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huiman","family":"Barnhart","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jay H.","family":"Hoofnagle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"R1-33-20250207","doi-asserted-by":"crossref","first-page":"730","DOI":"10.1002\/hep.23696","article-title":"Standardization of nomenclature and causality assessment in druginduced liver injury: summary of a clinical research workshop.","volume":"52","author":"Fontana","year":"2010","journal-title":"Hepatology"},{"key":"R2-33-20250207","doi-asserted-by":"crossref","first-page":"947","DOI":"10.7326\/0003-4819-137-12-200212170-00007","article-title":"Results of a prospective study of acute liver failure at 17 tertiary care centers in the United States.","volume":"137","author":"Ostapowicz","year":"2002","journal-title":"Ann Intern Med"},{"key":"R3-33-20250207","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1080\/01926230590522356","article-title":"Recognizing druginduced liver injury: current problems, possible solutions.","volume":"33","author":"Lee","year":"2005","journal-title":"Toxicol Pathol"},{"key":"R4-33-20250207","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1016\/j.cld.2007.06.003","article-title":"Causality assessment of druginduced hepatotoxicity: promises and pitfalls.","volume":"11","author":"Shapiro","year":"2007","journal-title":"Clin Liver Dis"},{"key":"R6-33-20250207","doi-asserted-by":"crossref","first-page":"364","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":"R7-33-20250207","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1136\/jcp.2008.058248","article-title":"Histological patterns in druginduced liver disease.","volume":"62","author":"Ramachandran","year":"2009","journal-title":"J Clin Pathol"},{"key":"R8-33-20250207","doi-asserted-by":"crossref","first-page":"55","DOI":"10.2165\/00002018-200932010-00005","article-title":"DrugInduced Liver Injury Network (DILIN) prospective study: rationale, design and conduct.","volume":"32","author":"Fontana","year":"2009","journal-title":"Drug Saf"},{"key":"R10-33-20250207","first-page":"A773","article-title":"Relationship of biochemical to histologic findings and the pathological pattern of injury among cases identified in the NIH DrugInduced Liver Injury Network (DILIN) Study.","volume":"132","author":"Kleiner","year":"2007","journal-title":"Gastroenterology"},{"key":"R14-33-20250207","doi-asserted-by":"crossref","first-page":"1323","DOI":"10.1016\/0895-4356(93)90101-6","article-title":"Causality assessment of adverse reactions to drugsI. A novel method based on the conclusions of international consensus meetings: application to druginduced liver injuries.","volume":"46","author":"Danan","year":"1993","journal-title":"J Clin Epidemiol"},{"key":"R15-33-20250207","doi-asserted-by":"crossref","first-page":"696","DOI":"10.1016\/0168-8278(95)80226-6","article-title":"Histological grading and staging of chronic hepatitis.","volume":"22","author":"Ishak","year":"1995","journal-title":"J Hepatol"},{"key":"R16-33-20250207","doi-asserted-by":"crossref","first-page":"1225","DOI":"10.1111\/j.1478-3231.2006.01377.x","article-title":"Liver regeneration in acute severe liver impairment: a clinicopathological correlation study.","volume":"26","author":"Katoonizadeh","year":"2006","journal-title":"Liver Int"},{"key":"R17-33-20250207","doi-asserted-by":"crossref","first-page":"1411","DOI":"10.1111\/j.1365-2036.2007.03330.x","article-title":"The impact of eosinophilia and hepatic necrosis on prognosis in patients with druginduced liver injury.","volume":"25","author":"Bjornsson","year":"2007","journal-title":"Aliment Pharmacol Ther"},{"key":"R18-33-20250207","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1016\/S0168-8278(86)80031-9","article-title":"Chronic liver disease after low daily doses of amiodarone. Report of three cases.","volume":"3","author":"Babany","year":"1986","journal-title":"J Hepatol"},{"key":"R19-33-20250207","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1016\/0002-9343(80)90443-X","article-title":"Adverse reactions to nitrofurantoin. Analysis of 921 reports.","volume":"69","author":"Holmberg","year":"1980","journal-title":"Am J Med"},{"key":"R20-33-20250207","first-page":"497","article-title":"Nitrofurantoininduced chronic liver disease. Clinical course and outcome of five cases.","volume":"14","author":"Iwarson","year":"1979","journal-title":"Scand J Gastroenterol"},{"key":"R22-33-20250207","doi-asserted-by":"crossref","first-page":"931","DOI":"10.1002\/hep.24481","article-title":"The use of liver biopsy evaluation in discrimination of idiopathic autoimmune hepatitis versus druginduced liver injury.","volume":"54","author":"Suzuki","year":"2011","journal-title":"Hepatology"}],"container-title":["Hepatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fhep.26709","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/hep.26709","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/hep.26709","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.lww.com\/01515467-201402000-00033","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,7]],"date-time":"2025-02-07T11:54:37Z","timestamp":1738929277000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.lww.com\/01515467-201402000-00033"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,2]]},"references-count":16,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2014]]}},"URL":"https:\/\/doi.org\/10.1002\/hep.26709","relation":{},"ISSN":["0270-9139"],"issn-type":[{"value":"0270-9139","type":"print"}],"subject":[],"published":{"date-parts":[[2014,2]]}}}