Abstract:
OBJECTIVE To explore the influencing factors for invasive fungal infection(IFI)-induced liver injury in patients who were treated with voriconazole and observe the CYP2 C19 gene polymorphisms.
METHODS A prospective study was conducted for 135 patients with IFI who were treated in the First Affiliated Hospital of Hainan Medical University from Jan 2017 to Dec 2019. All of the patients were given with voriconazole injection for treatment of fungal infection on basis of treatment of primary diseases. The blood concentrations were monitored, curative effects and drug-induced adverse reactions were observed, the CYP2 C19 gene polymorphisms were detected, the concentration min(Cmin), curative effects and adverse reactions of voriconazole were compared among the groups, and the influencing factors for the liver injury were analyzed.
RESULTS Among the 135 patients with IFI, 45.19% had genotype CYP2 C19*1/*1, 21.48% had genotype CYP2 C19*1/*2, 12.59% had genotype CYP2 C19*1/*3, 5.93% had genotype CYP2 C19*2/*2, 9.63% had genotype CYP2 C19*2/*3, and 5.19% had CYP2 C19*3/*3 genotype. The patients were divided into the fast metabolism(EM) group with 61 cases, the moderate metabolism(IM) group with 46 cases and the slow metabolism(PM) group with 28 cases according to the CYP2 C19 gene polymorphism. There was significant difference in the Cmin of voriconazole among the IFI patients with the three types of metabolisms(
P<0.05), there was no significant difference in the curative effect; the incidence of adverse reactions of the PM group was significantly higher than that of the EM group and the IM group(
P<0.05). Complication with liver injury before medication, age and PM were the independent risk factors for the liver injury caused by voriconazole(
P<0.05).
CONCLUSION The mutations of CYP2 C19*2 and CYP2 C19*3 are very common among the IFI patients in China, have remarkable effect on the metabolism of voriconazole and result in the increase of risk of liver injury, therefore, it is necessary to strengthen the surveillance of liver function of the PM patients during the medication.