Risk assessment of micafungin-induced liver injury using spontaneous reporting system data and electronic medical records

Introduction: There is limited information regarding antifungal-induced liver injuries, which have high mortality rates. Therefore, we used the Japanese Adverse Drug Event Report (JADER) database for signal detection associated with antifungal-induced liver injuries and medical records for risk assessment.& nbsp;Methods: Reports of antifungal-induced liver injuries from JADER data were analyzed to calculate the reporting odds ratio (ROR) and 95% confidence interval (CI). A medical record-based study involving 109 adult patients treated with micafungin shows liver injury as the primary outcome in patients treated with micafungin. The albumin-bilirubin (ALBI) score was calculated based on albumin and total bilirubin levels. We selected five explanatory factors for multivariable logistic regression: alanine aminotransferase >= 20 IU/L, alkaline phosphatase >= 372 IU/L, aspartate aminotransferase >= 25 IU/L, ALBI score >=-1.290, and age >= 65 years.& nbsp;Results: Signal detection for micafungin was observed in both, hepatocellular and cholestatic injuries, as per data from JADER. Univariate analyses performed on medical records suggest that alanine aminotransferase (p = 0.008), aspartate aminotransferase (p = 0.036), alkaline phosphatase (p = 0.045), and ALBI score (p = 0.028) may be factors associated with micafungin-induced liver injury. Based on multivariable logistic regression, the adjusted odds ratio for micafungin-induced liver injury in patients with ALBI score >=-1.290 was 2.78 (95% CI: 1.014-7.605, p = 0.047), suggesting that low hepatic functional reserve could be a risk factor for micafungininduced liver injury.& nbsp;Conclusions: Careful monitoring of liver function may be necessary for micafungin administration in patients with low hepatic functional reserve.

Automated summary

This study made important progress in elucidating the feasibility and relevant factors of micafungin-induced liver injury by using the JADER database for signal detection associated with antifungal-induced liver injuries and medical records for risk assessment.