| アブストラクト | BACKGROUND: The US Food and Drug Administration (FDA) recently issued a safety alert regarding cholestasis as a potential adverse reaction to immune checkpoint inhibitor (ICI) therapy. However, the underlying mechanisms of ICI-induced cholestasis remain poorly elucidated. METHODS: This study analyzed adverse event reports of cancer patients treated with ICIs, extracted from the FAERS (2013-2023) and VigiBase (1968-2023) databases. The reporting odds ratio (ROR) and information component (IC) methods were employed to evaluate the association between cholestasis and ICIs therapy, while time-to-onset (TTO) analysis was conducted. Clinical data from hospitals and results from mouse experiments were integrated to validate the analysis findings. RESULTS: Both ROR and IC analyses demonstrated a statistically significant elevation in cholestasis risk among ICI-treated patients compared to those receiving conventional chemotherapy. A heightened risk was observed in the 0-65 age cohort, with no significant gender-specific disparities noted. The TTO analysis revealed a delayed onset of cholestasis in both ICI-treated patients and female subjects compared to their respective counterparts. Gene expression profiling elucidated multiple cholestasis-associated signaling pathways, encompassing biliary inflammation, bile acid metabolic disorders, and impairment of hepatocellular drug metabolism. CONCLUSION: ICI-treated patients exhibit a higher cholestasis risk compared to conventional chemotherapy. Long-term liver function monitoring is crucial for patient safety. ICI-related cholestasis may result from immune-mediated bile duct injury or metabolic disorders, potentially influenced by baseline liver function. This comprehensive article provides crucial evidence for the risk assessment and management of ICI-related cholestasis, thereby contributing to safe medication use and enhanced patient care in clinical practice. |
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| 投稿者 | Yan, Xinrong; Li, Zhengrui; Jiang, Aimin; Chen, Jinghong; Huang, Xufeng; Hajdu, Andras; Wong, Hank Z H; Cheng, Quan; Zhang, Jian; Lin, Anqi; Luo, Peng |
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| 組織名 | Department of Oncology, Zhujiang Hospital, The First School of Clinical Medicine,;Southern Medical University; Donghai County People's Hospital (Affiliated Kangda;College of Nanjing Medical University), Lianyungang, China.;Department of Oral and Cranio-Maxillofacial Surgery, Shanghai Ninth People's;Hospital, College of Stomatology, Shanghai Jiao Tong University School of;Medicine, National Clinical Research Center for Oral Diseases, Shanghai Key;Laboratory of Stomatology, and Shanghai Research Institute of Stomatology,;Shanghai, China.;Department of Urology, Changhai Hospital, Naval Medical University (Second;Military Medical University), Shanghai, China.;Department of Data Visualization, Faculty of Informatics, University of Debrecen,;Debrecen, Hungary.;Faculty of Dentistry, University of Debrecen, Debrecen, Hungary.;Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR,;China.;Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha,;Hunan, China.;National Clinical Research Center for Geriatric Disorders, Xiangya Hospital,;Central South University, Hunan, China.;Department of Oncology, Zhujiang Hospital, Southern Medical University, Guangzhou |
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