{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T14:04:41Z","timestamp":1787061881602,"version":"build-2736575974"},"reference-count":52,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2026,1,2]],"date-time":"2026-01-02T00:00:00Z","timestamp":1767312000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100018712","name":"Iuliu Ha\u021bieganu University of Medicine and Pharmacy","doi-asserted-by":"publisher","award":["32152\/14\/16.12.2024"],"award-info":[{"award-number":["32152\/14\/16.12.2024"]}],"id":[{"id":"10.13039\/501100018712","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Drug-induced liver injury (DILI) remains one of the most challenging adverse drug reactions in clinical practice, particularly in its idiosyncratic form, which is not dose-dependent and is largely driven by host-specific immune and genetic factors. Recent genomic studies have revealed strong associations between certain human leukocyte antigen (HLA) alleles and susceptibility to DILI, supporting an immunogenetic mechanism in which drug or metabolite\u2013protein adducts act as neoantigens, triggering aberrant T-cell activation and hepatocellular injury. This review summarizes current evidence on the contribution of HLA polymorphisms to the pathogenesis of idiosyncratic DILI, highlighting allele-specific risk patterns, such as HLA-B*57:01 associated with flucloxacillin, HLA-DRB1*15:01\u2013DQB1*06:02 in amoxicillin\u2013clavulanate, and HLA-B*35:02 in minocycline-induced liver injury. Furthermore, ethnic variability and allele-haplotype interactions are discussed as potential modulators of susceptibility and clinical phenotype. By integrating genetic and immunological insights, the identification of HLA signatures offers promising tools for precision medicine, enabling earlier identification of at-risk individuals and improved prevention of severe hepatotoxic reactions.<\/jats:p>","DOI":"10.3390\/ijms27010482","type":"journal-article","created":{"date-parts":[[2026,1,2]],"date-time":"2026-01-02T12:23:44Z","timestamp":1767356624000},"page":"482","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Human Leukocyte Antigen (HLA) Signatures and Idiosyncratic Drug-Induced Liver Injury"],"prefix":"10.3390","volume":"27","author":[{"given":"Alexia","family":"Onaciu","sequence":"first","affiliation":[{"name":"Faculty of Medicine, \u201cIuliu Ha\u021bieganu\u201d University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alina","family":"Grama","sequence":"additional","affiliation":[{"name":"2nd Pediatric Discipline, Department of Mother and Child, Faculty of Medicine, \u201cIuliu Hatieganu\u201d University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania"},{"name":"2nd Pediatric Clinic, Emergency Clinical Hospital for Children, 400370 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u0218tefan","family":"Ago\u0219ton","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, \u201cIuliu Ha\u021bieganu\u201d University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Mititelu","sequence":"additional","affiliation":[{"name":"2nd Pediatric Discipline, Department of Mother and Child, Faculty of Medicine, \u201cIuliu Hatieganu\u201d University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania"},{"name":"2nd Pediatric Clinic, Emergency Clinical Hospital for Children, 400370 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bianca","family":"Mari\u015f","sequence":"additional","affiliation":[{"name":"2nd Pediatric Discipline, Department of Mother and Child, Faculty of Medicine, \u201cIuliu Hatieganu\u201d University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania"},{"name":"2nd Pediatric Clinic, Emergency Clinical Hospital for Children, 400370 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4034-5471","authenticated-orcid":false,"given":"Horia","family":"\u015etef\u0103nescu","sequence":"additional","affiliation":[{"name":"\u201cProf. Dr. Octavian Fodor\u201d Regional Institute of Gastroenterology and Hepatology, 400162 Cluj-Napoca, Romania"},{"name":"Department of Internal Medicine, \u201cIuliu Ha\u021bieganu\u201d University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4931-1219","authenticated-orcid":false,"given":"Tudor Lucian","family":"Pop","sequence":"additional","affiliation":[{"name":"2nd Pediatric Discipline, Department of Mother and Child, Faculty of Medicine, \u201cIuliu Hatieganu\u201d University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania"},{"name":"2nd Pediatric Clinic, Emergency Clinical Hospital for Children, 400370 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1038\/s41572-019-0105-0","article-title":"Drug-Induced Liver Injury","volume":"5","author":"Andrade","year":"2019","journal-title":"Nat. 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