Prospective cohort study finds that elevated voriconazole trough concentrations drive liver injury in pediatric stem cell transplant recipients, highlighting the need for drug monitoring.
Purpose We aimed to investigated the influencing risk factors of voriconazole-induced liver injury in Uygur pediatric patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT). Methods This was a prospective cohort design study. High-performance liquid chromatography-mass spectrometry was employed to monitor voriconazole concentration. First-generation sequencing was performed to detect gene polymorphisms. Indicators of liver function were detected at least once before and after voriconazole therapy. Results Forty-one patients were included in this study, among which, 15 patients (36.6%) had voriconazole-induced liver injury. The proportion of voriconazole trough concentration > 5.5 μg·mL −1 patients within the DILI group (40.0%) was significantly higher compared to the control group (15.4%) ( p < 0.05). After administration of voriconazole, the values of ALT (103.3 ± 80.3 U/L) and AST (79.9 ± 60.6 U/L) in the DILI group were higher than that in the control group (24.3 ± 24.8 and 30.4 ± 8.6 U/L) ( p < 0.05). There was no significant difference between the two groups in genotype and allele frequencies of CYP2C19*2 , CYP2C19*3 , CYP2C19*17 , and UGT1A4 (rs2011425) ( p > 0.05). Conclusion There was a significant correlation between voriconazole-induced liver injury and voriconazole trough concentration in high-risk Uygur pediatric patients with allogeneic HSCT.
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