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We retrospectively analysed clinical presentation and liver histology of 29 PPC-patients with hepatic disease of unknown origin and validated the data in a second independent prospective cohort of 36 cases. According to causality assessment score (CIOMS), overall 50 cases were highly suggestive of PPC-induced hepatitis (PIH), 5 cases were doubtful and 10 cases could be ruled out with highest probability. Histologically, acute or subacute hepatitis with characteristic centrilobular and\/or bridging necrosis was present and only minimal inflammatory infiltrate mainly consisting of ceroid-laden macrophages. The clinical presentation ranged from elevated aminotransferases in the absence of clinical symptoms to acute liver failure in 9 patients (18%) necessitating liver transplantation. Complete recovery after drug cessation was seen in 41 patients. Hepatic disease occurred 4 to 9\u00a0months after initiation of PPC treatment in 46 PIH cases and 1 to 6\u00a0weeks after reexposure in 5 PIH cases, so PPC was often not considered causative and liver biopsy was critical in supporting the diagnosis, as autoimmune hepatitis and other causes of TA elevations could be excluded. PIH-patients were significantly more often female (70% versus 49%) and of younger age (60.1 versus 71.9\u00a0years) when compared to non-hepatic PPC adverse reactions in the literature. PIH is a potentially life-threatening adverse reaction with characteristic histology, clinical presentation and course, suspicious of idiosyncratic metabolic injury. Our data suggest liver transaminase controls 3\u20134\u00a0months after PPC treatment start. Complete omission of PPC prevents progression of liver injury, as reexposure appears faster and more severe.<\/jats:p>","DOI":"10.1007\/s00428-026-04497-z","type":"journal-article","created":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T12:27:51Z","timestamp":1775651271000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Characteristic histopathology of phenprocoumon-induced liver injury: correlation with clinical presentation and outcome"],"prefix":"10.1007","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4857-1561","authenticated-orcid":false,"given":"B. 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Liver Int 45(3):e70012. https:\/\/doi.org\/10.1111\/liv.70012","journal-title":"Liver Int"}],"container-title":["Virchows Archiv"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00428-026-04497-z.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00428-026-04497-z","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00428-026-04497-z.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T12:27:54Z","timestamp":1775651274000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00428-026-04497-z"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,8]]},"references-count":50,"alternative-id":["4497"],"URL":"https:\/\/doi.org\/10.1007\/s00428-026-04497-z","relation":{},"ISSN":["0945-6317","1432-2307"],"issn-type":[{"value":"0945-6317","type":"print"},{"value":"1432-2307","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,8]]},"assertion":[{"value":"21 December 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 February 2026","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 March 2026","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 April 2026","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The investigation was approved by the local ethical committees of the University of Cologne, University Hospital Heidelberg (205\/2005 and 206\/2006) and University Medicine Mainz\/Landes\u00e4rztekammer Rhineland-Palatinate (837.360.16 (10679)).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}},{"value":"No patient consent was obtained as data analysis was retrospective in nature, anonymous and no identifying images or informations are shown.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Patient consent statement"}},{"value":"The work was supported in part by a grant of the Federal Ministry of Education and Research BMBF to KB (e:Bio_MS_DiLi; FKZ 031L0074H).","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Statement of financial support"}},{"value":"VD has accepted fees for speaking and for writing about the histopathology of hepatitis C at two conferences and the website\n                      \n                      from Hofmann La Roche, main producer of phenprocoumon (Marcumar\n                      \u00a9\n                      ). PS has received speaker and consultation fees from Hofmann La Roche on other topics. BKS has received speaker and consultation fees from Bayer Healthcare, Bristol Myers Squibb, Boehringer Ingelheim, Astra Zeneca, med update as well as IMPP and holds a scientific cooperation with Resolve Biosciences, but not on the topic of drug-induced liver injury. All other authors declare no conflict of interest.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest disclosure"}}]}}