Editorial
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Jul 18, 2015; 7(14): 1828-1833
Published online Jul 18, 2015. doi: 10.4254/wjh.v7.i14.1828
Voriconazole and the liver
Romeo-Gabriel Mihăilă
Romeo-Gabriel Mihăilă, Faculty of Medicine, Lucian Blaga University of Sibiu, 550169 Sibiu, Romania
Author contributions: Mihăilă RG solely contributed to this manuscript.
Conflict-of-interest statement: The author has no conflict-of-interest related to this article.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Romeo-Gabriel Mihăilă, MD, PhD, Faculty of Medicine, Lucian Blaga University of Sibiu, Str Lucian Blaga, 2A, 550169 Sibiu, Romania. romeomihaila@yahoo.com
Telephone: +40-269-215050 Fax: +40-269-218365
Received: January 21, 2015
Peer-review started: January 21, 2015
First decision: February 7, 2015
Revised: February 21, 2015
Accepted: April 10, 2015
Article in press: April 14, 2015
Published online: July 18, 2015
Processing time: 184 Days and 15.8 Hours
Abstract

Voriconazole is an azole useful for the prophylaxis and the treatment of aspergillosis and other fungal infections in immunosuppressed subjects, as those found in aplasia after aggressive polychemotherapy treatments, after hematopoietic stem cell, liver or lung transplantation. Its administration in therapeutic doses lead to extremely varied serum levels from patient to patient and even to the same patient. The explanations are varied: nonlinear pharmacokinetics, certain patient-related factors, including genetic polymorphisms in the cytochrome P450 2C19 gene, the kidney and liver function, simultaneous administration with other drugs metabolised by the same cytochrome. It is recommended to maintain the serum concentrations of voriconazole between 1.5 and 4 μg/mL. At lower values its efficacy decreases and at higher values the risk of neurological toxicity increases. Even at these concentrations it is not excluded the possible appearance of a variety of toxic effects, including on the liver, manifested by cholestasis, hepatocytolisis, or their combination. It is recommended to monitor the clinical and laboratory evolution of all patients treated with voriconazole, and of the serum levels of the drug of those who belong to risk groups, even if there is still no consensus on this issue, given the lack of correlation between the serum level and the occurrence of adverse effects in many patients.

Keywords: CYP2C19; Pharmacokinetics; Liver toxicity; Therapeutic drug monitoring; Voriconazole

Core tip: Voriconazole is an azole useful for the prophylaxis and the treatment of aspergillosis and other fungal infections in immunosuppressed subjects. Its administration in therapeutic doses lead to extremely varied serum levels from patient to patient and even to the same patient. It is recommended to maintain the serum concentrations of voriconazole between 1.5 and 4 μg/mL. At lower values its efficacy decreases and at higher values the risk of neurological toxicity increases. Even at these concentrations it is not excluded the possible appearance of a variety of toxic effects, including on the liver, manifested by cholestasis, hepatocytolisis, or their combination.