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

ABSTRACT

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. 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. 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 micafungin-induced liver injury. CONCLUSIONS: Careful monitoring of liver function may be necessary for micafungin administration in patients with low hepatic functional reserve.