侵袭性真菌感染患者伏立康唑肝毒性的研究

OBJECTIVE: To explore the factors that association with voriconazole-related hepatotoxicity in patients with invasive fungal infections. METHODS: Voriconazole trough plasma concentrations(ρ_min) were measured by high-performance liquid chromatography(HPLC). Voriconazole-related hepatotoxicity was defined according to Common Terminology Criteria for Adverse Events(CTCAE), and the multivariate linear regression and classification and regression tree(CART) were used to explore the factors that association with hepatotoxicity. RESULTS: A total of 328 samples from 144 patients were measured, and 18 patients with signs of hepatotoxicity. There was a significant difference between the voriconazole ρ_min in patients with hepatotoxicity and those without hepatotoxicity [(3.49 ± 2.31) μg•mL^-1 vs (1.96 ± 1.48 ) μg•mL^-1, P < 0.05]. There is no significant difference of hepatotoxicity in patients with different age, sex and CYP2C19 genetic status. However, CART revealed that hepatotoxicity was more likely to happen in the following populations: ①female patients with voriconazole ρ_min≤ 2.89 μg•mL^-1; ②poor metabolizer with voriconazole ρ_min > 2.89 μg•mL^-1; ③non-poor metabolizer with voriconazole ρ_min > 2.89 μg•mL^-1 who received CYP2C19 inhibitor. CONCLUSION: Monitoring voriconazole ρ_min and liver function could benefit to the safety of voriconazole therapy in patients with invasive fungal infections.