Influencing risk factors of voriconazole-induced liver injury in Uygur pediatric patients undergoing allogeneic hematopoietic stem cell transplantation

TL;DR

The study identifies high voriconazole concentrations as a risk factor for liver injury in Uygur children undergoing stem cell transplants.

Contribution

The study reveals a significant correlation between voriconazole trough concentration and liver injury in Uygur pediatric HSCT patients.

Findings

40% of patients with liver injury had voriconazole trough concentration >5.5 μg·mL−1, compared to 15.4% in the control group.

Liver enzymes ALT and AST were significantly higher in patients with liver injury after voriconazole administration.

No significant differences in gene polymorphisms of CYP2C19 and UGT1A4 were found between groups.

Abstract

We aimed to investigated the influencing risk factors of voriconazole-induced liver injury in Uygur pediatric patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT).

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.

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).

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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