A 37‑year‑old woman in a phase‑I trial got serious liver damage after taking the GnRH‑like peptide alarelin acetate (150 µg daily). The injury cleared after stopping the drug and using liver‑support supplements. Genetic testing showed she carried a NUDT15 loss‑of‑function variant and certain HLA alleles that might make her more prone to this liver toxicity.

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. A 37-year-old female participant in a phase I clinical trial developed acute hepatocellular injury following subcutaneous administration of alarelin acetate (150&#x202f;&#x3bc;g/day). The Roussel Uclaf Causality Assessment Method (RUCAM) yielded a score of 6, indicating a "highly probable" causal relationship between the drug and liver injury. Hepatic enzyme levels normalized within 18&#x202f;days 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 <i>NUDT15</i> variant (*3/*3 diplotype) and human leukocyte antigen (<i>HLA</i>) risk alleles (<i>HLA-DRB1*15:01</i>, <i>HLA-DQB1*06:01</i>). 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.