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Updated: Jun 23, 2025
Human Liver Microphysiological System for Assessing Drug-Induced Liver Toxicity In Vitro
Published on: January 31, 2022
Liver injury associated with endothelin receptor antagonists: a pharmacovigilance study based on FDA adverse event
Jinjian Gu1, Yuting Guo2, Bin Wu2
1West China School of Pharmacy, Sichuan University, Chengdu, Sichuan, China.
Background:
Endothelin receptor antagonists are commonly used in clinical practice, with concerns about their hepatotoxicity.
Aim:
This study aimed to conduct a comprehensive pharmacovigilance study based on FDA adverse event reporting system data to evaluate the possible association between endothelin receptor antagonists and drug-induced liver injury.
Method:
Adverse event reports from FDA adverse event reporting system between January 2004 and December 2022 were analyzed. Disproportionality algorithms, including reporting odds ratio and information component, were used to evaluate the association between endothelin receptor antagonists and liver injury. Sex- and age-stratified analyses of drug-induced liver injury events were also conducted in relation to endothelin receptor antagonists.
Results:
Significant associations between bosentan, macitentan, and liver injury were identified. Bosentan showed a strong link with liver injury, with reporting odds ratios for cholestatic injury at 7.59 (95% confidence interval: 6.90-8.35), hepatocellular injury at 5.63 (5.29-6.00), and serious drug-related hepatic disorders events at 1.33 (1.24-1.43). Drug-induced liver injury signals associated with bosentan were detected in all age groups. Macitentan was associated with liver injury, with reporting odds ratios for hepatic failure at 1.64 (1.39-1.94), cholestatic injury at 1.62 (1.43-1.83), and serious drug-related hepatic disorders events at 1.40 (1.29-1.51). No drug-induced liver injury signal was detected for ambrisentan, and no significant sex differences were observed in drug-induced liver injury events.
Conclusion:
Both bosentan and macitentan are associated with liver injury. Routine monitoring of serum aminotransferase levels is recommended, especially in patients at higher risk of liver injury. Further research into drug-drug interactions involving endothelin receptor antagonists is warranted.
Insights
Endothelin receptor antagonists like bosentan and macitentan are linked to drug-induced liver injury. Healthcare providers should monitor liver function, especially in high-risk patients, due to these risks.
Area of Science:
- Pharmacovigilance and Drug Safety
- Hepatology
- Clinical Pharmacology
Background:
- Endothelin receptor antagonists (ERAs) are widely used clinically.
- Concerns exist regarding the potential hepatotoxicity of ERAs.
Purpose of the Study:
- To assess the association between ERAs and drug-induced liver injury (DILI).
- Utilized the FDA Adverse Event Reporting System (FAERS) for comprehensive pharmacovigilance.
Main Methods:
- Analyzed FAERS data from January 2004 to December 2022.
- Employed disproportionality algorithms (ROR, IC) to detect DILI signals.
- Conducted age- and sex-stratified analyses for DILI events.
Main Results:
- Bosentan and macitentan showed significant associations with liver injury.
- Bosentan linked to cholestatic, hepatocellular injury, and serious hepatic disorders.
- Macitentan associated with hepatic failure, cholestatic injury, and serious hepatic disorders.
Conclusions:
- Bosentan and macitentan use necessitates liver injury monitoring.
- Routine serum aminotransferase monitoring is advised for at-risk patients.
- Further investigation into ERA drug-drug interactions is recommended.
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