2.3 Analysis
We performed disproportionality analysis using the reporting odds ratio
(ROR) with relevant Confidential Interval (CI) to indicate the presence
of signals of potential increased risk of drug-related AE [9]. The
ROR was calculated by dividing the odds of hepatic dysfunction events
reporting for voriconazole by the odds of hepatic dysfunction events
reporting for the comparison drug. A signal of increased hepatic
dysfunction risk was defined as the lower limit of 95% CI exceed one
with the number of cases ≥3 [10].
To validate the robustness of the findings, we conducted five specific
comparisons: (1) compared voriconazole with the full database; (2)
compared voriconazole with the other triazole antifungal drugs:
fluconazole, itraconazole, posaconazole and isavuconazole; (3) compared
voriconazole with the echinocandins antifungal drugs: caspofungin,
micafungin and anidulafungin; (4) compared voriconazole with the polyene
antifungal drug amphotericin B; (5) compared voriconazole with the
5-fluorocytosine.
The primary outcomes were overall hepatic-related adverse events
compared with the full database and the other antifungal drugs (see
details in Supplementary Materials Table S3 ). The secondary
outcomes were the high frequency reporting of hepatic dysfunction events
(see details in Supplementary Materials Table S4/S5 ): hepatic
function abnormal, cholestasis, alanine aminotransferase increased,
blood alkaline phosphatase increased, aspartate aminotransferase
increased, liver function test abnormal, gamma-glutamyl transferase
increased, liver disorder, hepatocellular injury, blood bilirubin
increased.
All the data extraction were performed by Microsoft Access 2010, and the
statistical analyses were performed using SPSS 26.0.