Enhancing the identification of voriconazole-associated hepatotoxicity by targeted metabolomics

被引：3

作者：

Chiang, Yi-Hsuan ^{[1
]}

Cheng, Chih-Ning ^{[1
]}

Chuang, Pei-Jiun ^{[2
]}

Chen, Yee-Chun ^{[3
]}

Chen, Yi-Jing ^{[1
]}

Kuo, Ching-Hua ^{[1
,4
,5
,6
]}

Lin, Shu-Wen ^{[1
,2
]}

Chang, Lin-Chau ^{[1
]}

机构：

[1] Natl Taiwan Univ, Coll Med, Sch Pharm, Taipei, Taiwan

[2] Natl Taiwan Univ, Grad Inst Clin Pharm, Coll Med, Taipei, Taiwan

[3] Natl Taiwan Univ, Natl Taiwan Univ Hosp, Coll Med, Dept Internal Med, Taipei, Taiwan

[4] Natl Taiwan Univ, Natl Taiwan Univ Hosp, Coll Med, Dept Pharm, Taipei, Taiwan

[5] Natl Taiwan Univ, Canc Ctr, Coll Med,Metabol Core Lab, Ctr Genom & Precis Med, Taipei, Taiwan

[6] 33 Linsen S Rd, Taipei City 10050, Taiwan

来源：

INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS | 2024年 / 63卷 / 01期

关键词：

mycosis; antifungal therapy; azole; biomarker; drug-induced liver injury; INVASIVE FUNGAL-INFECTIONS; TROUGH CONCENTRATION; DRUG; ASPERGILLOSIS; EFFICACY; SAFETY; BIOMARKERS; GUIDELINES; MANAGEMENT; SOCIETY;

D O I：

10.1016/j.ijantimicag.2023.107028

中图分类号：

R51 [传染病];

学科分类号：

100401 ;

摘要：

Voriconazole-associated hepatotoxicity is a common condition that generally manifests as elevated liver enzymes and can lead to drug discontinuation. Careful monitoring of voriconazole-associated hepatotoxicity is needed but there are no specific plasma biomarkers for this condition. Metabolomics has emerged as a promising technique for investigating biomarkers associated with drug-induced toxicity. The aim of this study was to use targeted metabolomics to evaluate seven endogenous metabolites as potential biomarkers of voriconazole-associated hepatotoxicity. Patients undergoing therapeutic drug monitoring of voriconazole were classified into a hepatotoxicity group (18 patients) or a control group (153 patients). Plasma samples were analysed using ultra-high-performance liquid chromatography coupled to mass spectrometry. Metabolite concentrations in the two groups were compared. Areas under the receiver operating characteristic (AUROC) curves generated from logistic regressions were used to correlate the concentrations of these seven metabolites with voriconazole trough concentrations and conventional liver biochemistry tests. Glycocholate and alpha-ketoglutarate levels were significantly higher in the hepatotoxicity group compared with the control group (false discovery rate-corrected P < 0.001 and P = 0.024, respectively). The metabolites glycocholate (AUROC = 0.795) and alpha-ketoglutarate (AUROC = 0.696) outperformed voriconazole trough concentrations (AUROC = 0.555) and approached the performance of alkaline phosphatase (AUROC = 0.876) and total bilirubin (AUROC = 0.815). A panel of glycocholate combined with voriconazole trough concentrations (AUROC = 0.827) substantially improved the performance of voriconazole trough concentrations alone in predicting hepatotoxicity. In conclusion, the panel integrating glycocholate with voriconazole trough concentrations has great potential for identifying voriconazoleassociated hepatotoxicity.(c) 2023 Elsevier Ltd and International Society of Antimicrobial Chemotherapy. All rights reserved.

引用

页数：8

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