Real-world pharmacovigilance analysis of drug-induced liver injury in 18-65 years: Based on the FDA adverse event reporting system (FAERS).

BACKGROUND

Drug-induced liver injury (DILI) in adults aged 18-65 years remains understudied despite its clinical heterogeneity and rising incidence. This study aimed to characterize the epidemiology, associated factors, and drug-specific profiles of DILI in this demographic.

METHOD: Utilizing data from the FDA Adverse Event Reporting System (FAERS) (2004-2024), we analyzed 180,659 DILI cases in patients aged 18-65 years. Four disproportionality methods-Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multi-item Gamma Poisson Shrinker (MGPS)-were employed to identify drugs with significant DILI signals. Time-to-onset (TTO) and sex-specific differences were assessed after excluding cases with missing or implausible dates.

RESULT: Twelve drugs exhibited significant DILI signals. Drospirenone; ethinylestradiol (ROR = 16.34, 95%CI: 15.92-16.76), amoxicillin/clavulanic acid (ROR = 6.10, 95%CI: 5.69-6.54), sorafenib (ROR = 5.07, 95%CI: 4.74-5.43), and paracetamol (ROR = 8.76, 95%CI: 8.51-9.01) showed the strongest associations. Analgesics had the shortest median time-to-onset (1 day). Gender subgroup analysis revealed sex-biased hepatotoxicity: 11 drugs met all four criteria in females, with leflunomide (ROR = 4.66, 95%CI: 4.28-5.07) and pembrolizumab (ROR = 4.39, 95%CI: 4.07-4.74) showing strong signals; 14 drugs met the criteria in males, with lamivudine (ROR = 6.87, 95%CI: 6.23-7.58) and amoxicillin/clavulanic acid (ROR = 6.73, 95%CI: 6.08-7.44) among the highest.

CONCLUSION

This analysis identifies antibiotics, immunosuppressants, and hormonal agents as drugs with prominent DILI disproportionality signals in adults aged 18-65 years. The findings advocate for targeted hepatic monitoring and suggest that drug labels could reflect class-specific latency patterns. Sex-specific signal monitoring warrant further investigation.