{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T09:57:07Z","timestamp":1775123827402,"version":"3.50.1"},"reference-count":33,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T00:00:00Z","timestamp":1775088000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T00:00:00Z","timestamp":1775088000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Klinikum der Universit\u00e4t M\u00fcnchen"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Drug-induced liver injury (DILI) is associated with high mortality risk. However, no biomarker can reliably predict outcome. In order to identify baseline parameters that are associated with mortality the data of 268 prospectively collected DILI patients were analyzed. Multivariate logistic regression and receiver operating characteristic curves were used to identify the parameters being most predictive for a fatal outcome, as defined by orthotopic liver transplantation (OLT) or death. 10.4% of patients had a fatal outcome, which was associated with higher levels of transaminases, total bilirubin, INR and model for end-stage liver disease (MELD) scores (25 vs. 12,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.001). Multivariate analysis revealed that only MELD and aspartate aminotransferase (AST) were independently associated with a poor outcome, the MELD score in particular had an extraordinarily high c-statistic of 0.93 (95% CI: 0.87\u20130.97). At a cut-off of \u2265\u200920, MELD could predict a fatal outcome with a sensitivity and specificity of 88% and 81%. The predictive performance of the MELD score could even be enhanced by combing it with AST elevation: At a cut-off of \u2265\u200920 and \u2265\u200929.6xULN, respectively, positive and negative predictive values of 44% and 96% were observed, which were higher than for any other baseline parameter.\n                  <\/jats:p>","DOI":"10.1038\/s41598-026-44893-8","type":"journal-article","created":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T06:14:26Z","timestamp":1775110466000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Aspartate aminotransferase and model for end-stage liver disease reliably predict mortality in drug-induced liver injury"],"prefix":"10.1038","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7077-8078","authenticated-orcid":false,"given":"Sabine","family":"Weber","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Izabel","family":"Mircheva","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rochell","family":"Balakumar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julian","family":"Allgeier","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Didem","family":"Saka","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nirali","family":"Donga","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christian M.","family":"Lange","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexander L.","family":"Gerbes","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2026,4,2]]},"reference":[{"issue":"12","key":"44893_CR1","doi-asserted-by":"publisher","first-page":"947","DOI":"10.7326\/0003-4819-137-12-200212170-00007","volume":"137","author":"G Ostapowicz","year":"2002","unstructured":"Ostapowicz, G. et al. Results of a prospective study of acute liver failure at 17 tertiary care centers in the United States. Ann. Intern. Med. 137(12), 947\u2013954. https:\/\/doi.org\/10.7326\/0003-4819-137-12-200212170-00007 (2002).","journal-title":"Ann. Intern. Med."},{"issue":"9","key":"44893_CR2","doi-asserted-by":"publisher","first-page":"1380","DOI":"10.1038\/ajg.2012.138","volume":"107","author":"KT Suk","year":"2012","unstructured":"Suk, K. T. et al. A prospective nationwide study of drug-induced liver injury in Korea. Am. J. Gastroenterol. 107(9), 1380\u20131387. https:\/\/doi.org\/10.1038\/ajg.2012.138 (2012).","journal-title":"Am. J. Gastroenterol."},{"issue":"2","key":"44893_CR3","doi-asserted-by":"publisher","first-page":"451","DOI":"10.1053\/jhep.2002.34857","volume":"36","author":"C Sgro","year":"2002","unstructured":"Sgro, C. et al. Incidence of drug-induced hepatic injuries: A French population-based study. Hepatology 36(2), 451\u2013455. https:\/\/doi.org\/10.1053\/jhep.2002.34857 (2002).","journal-title":"Hepatology"},{"issue":"2","key":"44893_CR4","doi-asserted-by":"publisher","first-page":"512","DOI":"10.1016\/j.gastro.2005.05.006","volume":"129","author":"RJ Andrade","year":"2005","unstructured":"Andrade, R. J. et al. Drug-induced liver injury: An analysis of 461 incidences submitted to the Spanish registry over a 10-year period. Gastroenterology 129(2), 512\u2013521. https:\/\/doi.org\/10.1016\/j.gastro.2005.05.006 (2005).","journal-title":"Gastroenterology"},{"issue":"7","key":"44893_CR5","doi-asserted-by":"publisher","first-page":"1340","DOI":"10.1053\/j.gastro.2015.03.006","volume":"148","author":"N Chalasani","year":"2015","unstructured":"Chalasani, N. et al. Features and outcomes of 899 patients with drug-induced liver injury: The DILIN prospective study. Gastroenterology 148(7), 1340-1352e e1347. https:\/\/doi.org\/10.1053\/j.gastro.2015.03.006 (2015).","journal-title":"Gastroenterology"},{"issue":"4","key":"44893_CR6","doi-asserted-by":"publisher","first-page":"439","DOI":"10.3109\/00365521.2014.958094","volume":"50","author":"R Jeong","year":"2015","unstructured":"Jeong, R. et al. Model for end-stage liver disease score as a predictor of short-term outcome in patients with drug-induced liver injury. Scand. J. Gastroenterol. 50(4), 439\u2013446. https:\/\/doi.org\/10.3109\/00365521.2014.958094 (2015).","journal-title":"Scand. J. Gastroenterol."},{"issue":"4","key":"44893_CR7","doi-asserted-by":"publisher","first-page":"575","DOI":"10.1016\/j.cld.2013.07.001","volume":"17","author":"WM Lee","year":"2013","unstructured":"Lee, W. M. Drug-induced acute liver failure. Clin. Liver Dis. 17(4), 575\u2013586. https:\/\/doi.org\/10.1016\/j.cld.2013.07.001 (2013).","journal-title":"Clin. Liver Dis."},{"key":"44893_CR8","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23116049","volume":"23","author":"S Weber","year":"2022","unstructured":"Weber, S. & Gerbes, A. L. Challenges and future of drug-induced liver injury research-Laboratory tests. Int. J. Mol. Sci. 23, 11. https:\/\/doi.org\/10.3390\/ijms23116049 (2022).","journal-title":"Int. J. Mol. Sci."},{"issue":"1","key":"44893_CR9","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1353\/pbm.1968.0004","volume":"12","author":"HJ Zimmerman","year":"1968","unstructured":"Zimmerman, H. J. The spectrum of hepatotoxicity. Perspect. Biol. Med. 12(1), 135\u2013161. https:\/\/doi.org\/10.1353\/pbm.1968.0004 (1968).","journal-title":"Perspect. Biol. Med."},{"issue":"4","key":"44893_CR10","doi-asserted-by":"publisher","first-page":"1275","DOI":"10.1002\/hep.29283","volume":"66","author":"PH Hayashi","year":"2017","unstructured":"Hayashi, P. H. et al. Death and liver transplantation within 2 years of onset of drug-induced liver injury. Hepatology 66(4), 1275\u20131285. https:\/\/doi.org\/10.1002\/hep.29283 (2017).","journal-title":"Hepatology"},{"issue":"1","key":"44893_CR11","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1111\/liv.14271","volume":"40","author":"RJ Andrade","year":"2020","unstructured":"Andrade, R. J. & Robles-Diaz, M. Diagnostic and prognostic assessment of suspected drug-induced liver injury in clinical practice. Liver Int. 40(1), 6\u201317. https:\/\/doi.org\/10.1111\/liv.14271 (2020).","journal-title":"Liver Int."},{"issue":"1","key":"44893_CR12","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1053\/j.gastro.2014.03.050","volume":"147","author":"M Robles-Diaz","year":"2014","unstructured":"Robles-Diaz, M. et al. Use of Hy\u2019s law and a new composite algorithm to predict acute liver failure in patients with drug-induced liver injury. Gastroenterology 147(1), 109-118 e105. https:\/\/doi.org\/10.1053\/j.gastro.2014.03.050 (2014).","journal-title":"Gastroenterology"},{"issue":"2","key":"44893_CR13","doi-asserted-by":"publisher","first-page":"488","DOI":"10.1007\/s12072-022-10405-9","volume":"17","author":"Y Wang","year":"2023","unstructured":"Wang, Y. et al. Comparison of the prognostic models for mortality in idiosyncratic drug-induced liver injury. Hepatol. Int. 17(2), 488\u2013498. https:\/\/doi.org\/10.1007\/s12072-022-10405-9 (2023).","journal-title":"Hepatol. Int."},{"issue":"1","key":"44893_CR14","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1053\/j.gastro.2014.03.045","volume":"147","author":"RJ Fontana","year":"2014","unstructured":"Fontana, R. J. et al. Idiosyncratic drug-induced liver injury is associated with substantial morbidity and mortality within 6 months from onset. Gastroenterology 147(1), 96-108 e104. https:\/\/doi.org\/10.1053\/j.gastro.2014.03.045 (2014).","journal-title":"Gastroenterology"},{"issue":"9","key":"44893_CR15","doi-asserted-by":"publisher","first-page":"1382","DOI":"10.1038\/ajg.2017.215","volume":"112","author":"N Chalasani","year":"2017","unstructured":"Chalasani, N. et al. Idiosyncratic drug induced liver injury in African-Americans is associated with greater morbidity and mortality compared to Caucasians. Am. J. Gastroenterol. 112(9), 1382\u20131388. https:\/\/doi.org\/10.1038\/ajg.2017.215 (2017).","journal-title":"Am. J. Gastroenterol."},{"issue":"2","key":"44893_CR16","doi-asserted-by":"publisher","first-page":"661","DOI":"10.1002\/hep.26709","volume":"59","author":"DE Kleiner","year":"2014","unstructured":"Kleiner, D. E. et al. Hepatic histological findings in suspected drug-induced liver injury: Systematic evaluation and clinical associations. Hepatology 59(2), 661\u2013670. https:\/\/doi.org\/10.1002\/hep.26709 (2014).","journal-title":"Hepatology"},{"issue":"7","key":"44893_CR17","doi-asserted-by":"publisher","DOI":"10.1111\/liv.70182","volume":"45","author":"S Weber","year":"2025","unstructured":"Weber, S. et al. Histopathological changes as a predictor of fatal outcome in patients with drug-induced liver injury. Liver Int. 45(7), e70182. https:\/\/doi.org\/10.1111\/liv.70182 (2025).","journal-title":"Liver Int."},{"issue":"12","key":"44893_CR18","doi-asserted-by":"publisher","first-page":"1411","DOI":"10.1111\/j.1365-2036.2007.03330.x","volume":"25","author":"E Bjornsson","year":"2007","unstructured":"Bjornsson, E., Kalaitzakis, E. & Olsson, R. The impact of eosinophilia and hepatic necrosis on prognosis in patients with drug-induced liver injury. Aliment. Pharmacol. Ther. 25(12), 1411\u20131421. https:\/\/doi.org\/10.1111\/j.1365-2036.2007.03330.x (2007).","journal-title":"Aliment. Pharmacol. Ther."},{"issue":"4","key":"44893_CR19","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1002\/pds.1211","volume":"15","author":"R Temple","year":"2006","unstructured":"Temple, R. Hy\u2019s law: Predicting serious hepatotoxicity. Pharmacoepidemiol. Drug Saf. 15(4), 241\u2013243. https:\/\/doi.org\/10.1002\/pds.1211 (2006).","journal-title":"Pharmacoepidemiol. Drug Saf."},{"key":"44893_CR20","doi-asserted-by":"publisher","first-page":"442","DOI":"10.5604\/16652681.1235488","volume":"16","author":"C Rathi","year":"2017","unstructured":"Rathi, C. et al. Drug induced liver injury at a tertiary hospital in India: Etiology, clinical features and predictors of mortality. Ann. Hepatol. 16, 3, 442\u2013450. https:\/\/doi.org\/10.5604\/16652681.1235488 (2017).","journal-title":"Ann. Hepatol."},{"issue":"10","key":"44893_CR21","doi-asserted-by":"publisher","first-page":"2383","DOI":"10.1111\/liv.14985","volume":"41","author":"M Reike-Kunze","year":"2021","unstructured":"Reike-Kunze, M. et al. Drug-induced liver injury at a tertiary care centre in Germany: Model for end-stage liver disease is the best predictor of outcome. Liver Int. 41(10), 2383\u20132395. https:\/\/doi.org\/10.1111\/liv.14985 (2021).","journal-title":"Liver Int."},{"issue":"6","key":"44893_CR22","doi-asserted-by":"publisher","first-page":"806","DOI":"10.1038\/clpt.2011.58","volume":"89","author":"GP Aithal","year":"2011","unstructured":"Aithal, G. P. et al. Case definition and phenotype standardization in drug-induced liver injury. Clin. Pharmacol. Ther. 89(6), 806\u2013815. https:\/\/doi.org\/10.1038\/clpt.2011.58 (2011).","journal-title":"Clin. Pharmacol. Ther."},{"issue":"2","key":"44893_CR23","doi-asserted-by":"publisher","first-page":"481","DOI":"10.1002\/hep.20800","volume":"42","author":"E Bjornsson","year":"2005","unstructured":"Bjornsson, E. & Olsson, R. Outcome and prognostic markers in severe drug-induced liver disease. Hepatology 42(2), 481\u2013489. https:\/\/doi.org\/10.1002\/hep.20800 (2005).","journal-title":"Hepatology"},{"issue":"5","key":"44893_CR24","doi-asserted-by":"publisher","first-page":"1245","DOI":"10.1053\/j.gastro.2019.07.006","volume":"157","author":"M Ghabril","year":"2019","unstructured":"Ghabril, M. et al. Development and validation of a model consisting of comorbidity burden to calculate risk of death within 6 months for patients with suspected drug-induced liver injury. Gastroenterology 157(5), 1245\u20131252e. https:\/\/doi.org\/10.1053\/j.gastro.2019.07.006 (2019).","journal-title":"Gastroenterology"},{"issue":"6","key":"44893_CR25","doi-asserted-by":"publisher","first-page":"1222","DOI":"10.1016\/j.jhep.2019.02.014","volume":"70","author":"European Association for the Study of the Liver","year":"2019","unstructured":"European Association for the Study of the Liver. EASL clinical practice guidelines: Drug-induced liver injury. J. Hepatol. 70(6), 1222\u20131261. https:\/\/doi.org\/10.1016\/j.jhep.2019.02.014 (2019).","journal-title":"J. Hepatol."},{"issue":"9","key":"44893_CR26","doi-asserted-by":"publisher","first-page":"1488","DOI":"10.1016\/j.cgh.2018.04.049","volume":"16","author":"A Benesic","year":"2018","unstructured":"Benesic, A. et al. Development and validation of a test to identify drugs that cause idiosyncratic drug-induced liver injury. Clin. Gastroenterol. Hepatol. 16(9), 1488-1494 e1485. https:\/\/doi.org\/10.1016\/j.cgh.2018.04.049 (2018).","journal-title":"Clin. Gastroenterol. Hepatol."},{"issue":"6","key":"44893_CR27","doi-asserted-by":"publisher","first-page":"676","DOI":"10.1093\/aje\/kwq433","volume":"173","author":"H Quan","year":"2011","unstructured":"Quan, H. et al. Updating and validating the Charlson comorbidity index and score for risk adjustment in hospital discharge abstracts using data from 6 countries. Am. J. Epidemiol. 173(6), 676\u2013682. https:\/\/doi.org\/10.1093\/aje\/kwq433 (2011).","journal-title":"Am. J. Epidemiol."},{"issue":"11","key":"44893_CR28","doi-asserted-by":"publisher","first-page":"1323","DOI":"10.1016\/0895-4356(93)90101-6","volume":"46","author":"G Danan","year":"1993","unstructured":"Danan, G. & Benichou, C. Causality assessment of adverse reactions to drugs\u2013I. A novel method based on the conclusions of international consensus meetings: Application to drug-induced liver injuries. J. Clin. Epidemiol. 46(11), 1323\u20131330. https:\/\/doi.org\/10.1016\/0895-4356(93)90101-6 (1993).","journal-title":"J. Clin. Epidemiol."},{"issue":"1","key":"44893_CR29","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1111\/liv.15378","volume":"43","author":"ES Bjornsson","year":"2023","unstructured":"Bjornsson, E. S. et al. A new framework for advancing in drug-induced liver injury research. The Prospective European DILI Registry. Liver Int. 43(1), 115\u2013126. https:\/\/doi.org\/10.1111\/liv.15378 (2023).","journal-title":"Liver Int."},{"issue":"2","key":"44893_CR30","doi-asserted-by":"publisher","first-page":"439","DOI":"10.1016\/0016-5085(89)90081-4","volume":"97","author":"JG O'Grady","year":"1989","unstructured":"O\u2019Grady, J. G., Alexander, G. J., Hayllar, K. M. & Williams, R. Early indicators of prognosis in fulminant hepatic failure. Gastroenterology 97(2), 439\u2013445. https:\/\/doi.org\/10.1016\/0016-5085(89)90081-4 (1989).","journal-title":"Gastroenterology"},{"issue":"1","key":"44893_CR31","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1053\/gast.2003.50016","volume":"124","author":"R Wiesner","year":"2003","unstructured":"Wiesner, R. et al. Model for end-stage liver disease (MELD) and allocation of donor livers. Gastroenterology 124(1), 91\u201396. https:\/\/doi.org\/10.1053\/gast.2003.50016 (2003).","journal-title":"Gastroenterology"},{"issue":"2","key":"44893_CR32","doi-asserted-by":"publisher","first-page":"464","DOI":"10.1053\/jhep.2001.22172","volume":"33","author":"PS Kamath","year":"2001","unstructured":"Kamath, P. S. et al. A model to predict survival in patients with end-stage liver disease. Hepatology 33(2), 464\u2013470. https:\/\/doi.org\/10.1053\/jhep.2001.22172 (2001).","journal-title":"Hepatology"},{"issue":"5","key":"44893_CR33","doi-asserted-by":"publisher","first-page":"1047","DOI":"10.1016\/j.jhep.2016.12.003","volume":"66","author":"European Association for the Study of the Liver","year":"2017","unstructured":"European Association for the Study of the Liver et al. EASL clinical practical guidelines on the management of acute (fulminant) liver failure. J. Hepatol. 66(5), 1047\u20131081. https:\/\/doi.org\/10.1016\/j.jhep.2016.12.003 (2017).","journal-title":"J. Hepatol."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-44893-8","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-44893-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-44893-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T09:02:52Z","timestamp":1775120572000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-44893-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,2]]},"references-count":33,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["44893"],"URL":"https:\/\/doi.org\/10.1038\/s41598-026-44893-8","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,2]]},"assertion":[{"value":"23 November 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 March 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 April 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"11236"}}