{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T22:52:59Z","timestamp":1761864779662,"version":"3.44.0"},"reference-count":38,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,9,29]],"date-time":"2025-09-29T00:00:00Z","timestamp":1759104000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Alarelin acetate, a synthetic gonadotropin-releasing hormone (GnRH) analogue, is widely used to manage endometriosis and hormone-sensitive malignancies. Although its safety profile is generally favorable, we report the first documented case of severe hepatotoxicity associated with alarelin acetate administration.<\/jats:p><\/jats:sec><jats:sec><jats:title>Case summary<\/jats:title><jats:p>A 37-year-old female participant in a phase I clinical trial developed acute hepatocellular injury following subcutaneous administration of alarelin acetate (150\u202f\u03bcg\/day). The Roussel Uclaf Causality Assessment Method (RUCAM) yielded a score of 6, indicating a \u201chighly probable\u201d causal relationship between the drug and liver injury. Hepatic enzyme levels normalized within 18\u202fdays after drug discontinuation and initiation of hepatoprotective therapy (glycyrrhizin and polyene phosphatidylcholine). Pharmacogenomic profiling identified specific genetic variations that may be associated with alarelin acetate-related hepatotoxicity, including a homozygous <jats:italic>NUDT15<\/jats:italic> variant (*3\/*3 diplotype) and human leukocyte antigen (<jats:italic>HLA<\/jats:italic>) risk alleles (<jats:italic>HLA-DRB1*15:01<\/jats:italic>, <jats:italic>HLA-DQB1*06:01<\/jats:italic>).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This novel case highlights the risk of alarelin acetate-related hepatotoxicity. Pharmacogenomic profiling indicated that its hepatotoxicity may be related to gene polymorphisms; however, further research or larger-scale studies are needed to validate these associations.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fmed.2025.1634101","type":"journal-article","created":{"date-parts":[[2025,9,29]],"date-time":"2025-09-29T05:26:59Z","timestamp":1759123619000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Pharmacogenomic analysis of alarelin acetate-induced hepatotoxicity: a case report and literature 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