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Because of its unpredictability and clinical relevance, it is of medical concern. Three DILI phenotypes (hepatocellular, cholestatic, and mixed) are currently recognized, based on serum alanine aminotransferase (ALT) and alkaline phosphatase (ALP) values. However, this classification lacks accuracy to distinguish among the many intermediate mixed types, or even to estimate the magnitude and progression of the injury. It was found desirable to have additional elements for better evaluation criteria of DILI. With this aim, we have examined the serum metabolomic changes occurring in 79 DILI patients recruited and monitored using established clinical criteria, along the course of the disease and until recovery. Results revealed that free and conjugated bile acids, and glycerophospholipids were among the most relevant metabolite classes for DILI phenotype characterization. Using an ensemble of PLS\u2013DA models, metabolomic information was integrated into a ternary diagram to display the disease phenotype, the severity of the liver damage, and its progression. The modeling implemented and the use of such compiled information in an easily understandable and visual manner facilitates a straightforward DILI phenotyping and allow to monitor its progression and recovery prediction, usefully complementing the concise information drawn out by the ALT and ALP classification.<\/jats:p>","DOI":"10.1007\/s00204-021-03114-z","type":"journal-article","created":{"date-parts":[[2021,7,17]],"date-time":"2021-07-17T16:02:33Z","timestamp":1626537753000},"page":"3049-3062","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":52,"title":["Metabolomic analysis to discriminate drug-induced liver injury (DILI) phenotypes"],"prefix":"10.1007","volume":"95","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4240-9846","authenticated-orcid":false,"given":"Guillermo","family":"Quint\u00e1s","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teresa","family":"Mart\u00ednez-Sena","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabel","family":"Conde","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2998-9794","authenticated-orcid":false,"given":"Eugenia","family":"Pareja Ibars","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6421-138X","authenticated-orcid":false,"given":"Jos","family":"Kleinjans","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1179-6430","authenticated-orcid":false,"given":"Jos\u00e9 V.","family":"Castell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,7,17]]},"reference":[{"key":"3114_CR1","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1111\/j.1365-2125.2004.02133.x","volume":"58","author":"FJD Abajo","year":"2004","unstructured":"Abajo FJD, Montero D, Madurga M, Rodr\u00edguez LAG (2004) Acute and clinically relevant drug-induced liver injury: a population based case-control study. 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