The Predictive Value of Initial Trough Concentration of Voriconazole and Procalcitonin in Hepatotoxic Adverse Events

This study aimed to evaluate the predictive value of initial trough concentration (C_min) of voriconazole (VCZ) and procalcitonin (PCT) in hepatotoxic adverse events.

A retrospective analysis was performed on clinical data from 170 patients administered VCZ at our institution between January 2021 and July 2025. Risk factors associated with VCZ-induced hepatotoxicity were identified through binary logistic regression analysis. The diagnostic performance of initial VCZ-C_min and PCT in predicting hepatotoxicity was evaluated using receiver operating characteristic (ROC) curve analysis.

The mean loading dose of VCZ was 9.48 mg/kg, with a maintenance dose of 6.62 mg/kg, and an average initial C_min of 5.58 mg/L. Hepatotoxicity was observed in 20.59% (35/170) of patients during the treatment period. Multivariate logistic regression analysis, adjusted for confounding factors including weight, maintenance dose, and proton pump inhibitors use, revealed that elevated initial VCZ-C_min and high PCT levels were significantly associated with hepatotoxicity. ROC curve analysis identified critical thresholds for hepatotoxicity risk: an initial VCZ-C_min of 5.035 mg/L (AUC=0.663, P=0.003) and a PCT level of 0.835 ng/mL (AUC=0.754, P<0.001), the predictive probability of their combination was 0.184 (AUC=0.744, P<0.001). After grouping according to the threshold level of PCT, there was a significant difference in the initial VCZ-C_min between patients with high PCT levels and those with low PCT levels (P=0.005).

VCZ-induced hepatotoxicity is the common adverse reaction, exhibiting significant associations with elevated initial VCZ-C_min and increased PCT levels. Both the initial VCZ-C_min and PCT levels are independent risk factors, and either alone or in combination can predict the occurrence of hepatotoxicity. Among these, PCT levels have the most significant predictive value.