Work

Pharmacogenomic analysis of alarelin acetate-induced hepatotoxicity: a case report and literature review

Year: 2025

Type: article

Abstract: Background 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. Case summary A 37-year-old female participant in a phase I clinical trial developed acute hepatocellular injury following subcutaneous administration of alarelin acetate (150 μg/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 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 NUDT15 variant (*3/*3 diplotype) and human leukocyte antigen (HLA) risk alleles (HLA-DRB1*15:01, HLA-DQB1*06:01). Conclusion 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.

Source: Frontiers in Medicine

DOI: 10.3389/fmed.2025.1634101

Authors: Fang Yuan, Ping Zhang, Ming Liu, Yuan Li, Bin Xu, Xin Li

Institutions: Hunan University, China Academy of Chinese Medical Sciences, Third Hospital of Changsha

Language: English

Topic: Drug-Induced Hepatotoxicity and Protection

Subfield: Pharmacology

Field: Pharmacology, Toxicology and Pharmaceutics

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,801