Voriconazole-Induced Hepatotoxicity in a Patient with Pulmonary Aspergillosis: A Case Report

Abstract

Voriconazole is the therapy of choice for aspergillosis. However, hepatotoxicity is the most common reason for the discontinuation of voriconazole. In contrast, posaconazole is well tolerated, with a low incidence of hepatotoxicity. In most cases, hepatotoxicity is associated with high voriconazole trough concentration influenced mainly by cytochrome P450 (CYP) 2C19 gene polymorphism. Compared with normal metabolizers, intermediate and poor metabolizers generally have higher voriconazole trough concentrations with an increased risk of hepatotoxicity. Here, we describe changes in hepatotoxicity throughout azole therapy in a patient with pulmonary aspergillosis (PA). Nevertheless, the patient with the normal metabolism genotype of CYP2C19 developed severe hepatotoxicity caused by voriconazole but tolerated posaconazole well, with a lack of direct cross-hepatotoxicity between the both. Interestingly, the patient had a high risk of hepatotoxicity at a low voriconazole trough concentration. Fortunately, elevated liver enzymes declined to the baselines with posaconazole treatment.

Keywords:

• hepatotoxicity
• drug-induced liver injury
• drug trough concentrations
• voriconazole
• posaconazole
• pulmonary aspergillosis

Abbreviations

CYP29C19, cytochrome P450 (CYP) 2C19; PA, pulmonary aspergillosis; IFD, invasive fungal diseases; ALT, alanine transaminase; AST, aspartate transaminase; APL, alkaline phosphatase; γ-GGT, gamma-glutamyl transpeptidase; ULN, the upper limit of normal; DILI, drug-induced liver injury; TDM, therapeutic drug monitoring; UM, ultrarapid metabolizers; RM, rapid metabolizers; NM, normal metabolizers; IM, intermediate metabolizers; PM, poor metabolizers.

Patient Consent and Ethics Statement

The patient provided informed consent for the publication of the case report. The ethical committee approval was not required for the case details.

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

The authors declare that they have no conflicts of interest in this work.

Additional information

Funding

This study did not receive any funding.