Published online Oct 26, 2020. doi: 10.12998/wjcc.v8.i20.4700
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
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.
To record the improving trend of liver function and the therapeutic effects in patients after lowering the trough concentration of voriconazole.
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.
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).
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.
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.