Retrospective Cohort Study
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Cases. Oct 26, 2020; 8(20): 4700-4707
Published online Oct 26, 2020. doi: 10.12998/wjcc.v8.i20.4700
Remission of hepatotoxicity in chronic pulmonary aspergillosis patients after lowering trough concentration of voriconazole
Guo-Jie Teng, Xiang-Rong Bai, Lin Zhang, Hong-Jun Liu, Xiu-Hong Nie
Guo-Jie Teng, Lin Zhang, Xiu-Hong Nie, Department of Pulmonary and Critical Care Medicine, Xuanwu Hospital Capital Medical University, Beijing 100053, China
Xiang-Rong Bai, Pharmacy Department, Xuanwu Hospital Capital Medical University, Beijing 100053, China
Hong-Jun Liu, Department of Evidence-based Medicine, Xuanwu Hospital Capital Medical University, Beijing, China, Beijing 100053, China
Author contributions: Teng GJ and Bai XR performed the diagnostic investigations and treatments; Teng GJ and Zhang L acquired the data and contributed to manuscript drafting; Teng GJ and Liu HJ were responsible for the statistics; Nie XH was responsible for revising the manuscript for important intellectual content; All authors issued final approval for the version to be submitted.
Institutional review board statement: The study was approved by the Institutional Review Board of Xuanwu Hospital, Capital Medical University, Beijing, No. 2019-118.
Informed consent statement: All study participants provided informed written consent about personal and medical data collection prior to study enrolment.
Conflict-of-interest statement: The authors declare that there is no conflict of interest regarding the publication of this manuscript.
Data sharing statement: The original anonymous dataset used and/or analyzed during the current study are available from the corresponding author on reasonable request.
STROBE statement: The authors have read the STROBE Statement-checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-checklist of items.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (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/
Corresponding author: Xiu-Hong Nie, PhD, Chief Doctor, Department of Pulmonary and Critical Care Medicine, Xuanwu Hospital Capital Medical University, No. 45 Changchun Street, Xicheng District, Beijing 100053, China. xiuhongnie@126.com
Received: May 17, 2020
Peer-review started: May 17, 2020
First decision: July 25, 2020
Revised: July 29, 2020
Accepted: September 1, 2020
Article in press: September 1, 2020
Published online: October 26, 2020
Processing time: 161 Days and 21.3 Hours
Abstract
BACKGROUND

Chronic pulmonary aspergillosis (CPA) is a rare syndrome that is often accompanied by gradual lung tissue destruction. Voriconazole is usually employed as the first-line agent for CPA treatment. However, some patients can develop hepatotoxicity and often were forced to stop voriconazole treatment.

AIM

To record the improving trend of liver function and the therapeutic effects in patients after lowering the trough concentration of voriconazole.

METHODS

This study retrospectively analyzed 12 adult CPA patients who developed hepatotoxicity during the voriconazole treatment. In these patients, the oral dose was reduced to 3/4 or 1/2 of the standard dose (4 mg/kg, twice daily), and the lower limit of voriconazole trough concentration was maintained more than 0.5 µg/mL. The trend of remission of liver toxicity after drug reduction in 12 patients was recorded. During the same period, 25 patients who received standard doses served as the control group. Data from the two groups were collected and analyzed for different parameters such as demographic characteristics, underlying pulmonary disorders, laboratory tests, and therapeutic effect. The differences between the two groups were statistically compared.

RESULTS

Hepatotoxicity occurred in 12 patients within 28-65 d after oral voriconazole treatment. Hepatotoxicity was mainly manifested by the significantly increased level of gamma-glutamyltransferase and a slight increase of alanine aminotransferase and aspartate aminotransferase. The oral dose of voriconazole was reduced to approximately 3 mg/kg in seven patients and approximately 2 mg/kg in five patients. The average trough concentrations for the 12 patients before and after voriconazole oral dose reduction were 3.17 ± 1.47 µg/mL (1.5-6.0 µg/mL) and 1.70 ± 0.78 µg/mL (0.6-3.3 µg/mL), respectively (P = 0.02). After lowering the trough concentrations, the hepatotoxicity was alleviated in all the patients. However, gamma-glutamyltransferase levels declined slowly. After 4 mo of treatment, 7 of the 12 patients were successfully treated in the low trough concentrations group (41.7%). Similarly, 8 of the 25 patients in the standard treatment dose group (32.0%) were effectively treated. There was no statistical difference between the groups (P = 0.72).

CONCLUSION

Reducing the lower limit of the voriconazole trough concentration to 0.5 µg/mL can alleviate the hepatotoxicity and maintained certain clinical efficacy in CPA patients; however, patients should be closely monitored.

Keywords: Voriconazole; Hepatotoxicity; Chronic pulmonary aspergillosis; CYP2C19 genotypes; Reduction; Trough concentration

Core Tip: In this retrospective study, we evaluated 12 adult chronic pulmonary aspergillosis patients who developed hepatotoxicity during voriconazole treatment. The hepatotoxicity mainly manifested as a significant increase in the level of gamma-glutamyltransferase. In some patients, gamma-glutamyltransferase can reach up to 6-20 times the upper limit. Overall findings recommend that reducing the lower limit of the voriconazole trough concentration to 0.5 µg/mL can alleviate the hepatotoxicity of chronic pulmonary aspergillosis patients and maintain the clinical efficacy.