伏立康唑导致的药物性肝损伤特征:基于CYP2C19基因代谢类型防治效果观察

doi:10.3969/j.issn.1672-5069.2025.06.018

摘要/Abstract

摘要： 目的观察伏立康唑诱发的药物性肝损伤(DILI)的特征,并基于CYP2C19基因代谢类型予以防治,观察效果。方法 2022年3月～2025年3月我院收治的肺真菌病(FDL)患者96例,被随机分为A组、B组和C组,每组32例。采用聚合酶链式反应-基因芯片法进行CYP2C19基因多态性检测。所有患者在伏立康唑抗真菌治疗的同时,A组未给予护肝药物,给予B组水飞蓟宾葡甲胺片治疗,C组11例CYP2C19基因快代谢型患者未给予护肝药物,给予11例中等代谢型患者水飞蓟宾葡甲胺片治疗,给予10例慢代谢型患者水飞蓟宾葡甲胺片联合多烯磷脂酰胆碱胶囊治疗。常规检测血清肝功能指标和超敏C反应蛋白(hs-CRP)水平,采用化学发光平台检测血清白介素6(IL-6)水平,采用分光光度法检测血清超氧化物歧化酶(SOD)和丙二醛(MDA)水平。结果在治疗6 w后,A组、B组和C组抗真菌治疗有效率分别为78.1%、75.0%和84.4%(P＞0.05); A组、B组和C组DILI发生率分别为21.9%、6.3%和3.1%,具有统计学差异(P＜0.05);B组和C组各代谢型患者血清ALT、AST和TBIL水平均显著低于A组,而C组慢代谢型患者血清ALT和AST水平均显著低于B组(P＜0.05);B组和C组各代谢型患者血清hs-CRP、IL-6和MDA水平均显著低于A组,而C组慢代谢型患者血清MDA水平显著低于B组(P＜0.05)。结论在伏立康唑治疗FDL的同时,给予护肝药物治疗,可能降低DILI发生,而根据CYP2C19基因代谢类型采取针对性的预防性护肝治疗可能更加精准和科学。

关键词: 药物性肝损伤, 肺真菌病, 伏立康唑, CYP2C19基因多态性, 预防

Abstract: Objective The aim of this study was to investigate prevention of drug-induced liver injury (DILI) based on CYP2C19 gene polymorphism in patients with fungal disease of lung (FDL) undergoing voriconazole therapy. Methods 96 patients with FDL were admitted to our hospital between March 2022 and March 2025, and were randomly divided into group A, group B and group C, with 32 cases in each group. CYP2C19 gene polymorphism was detected by PCR-gene chip. All patients received voriconazole antifungal treatment, and simultaneously, no hepatoprotective medicine was given in group A, silybin glucoside was given in group B, and in group C, no hepatoprotective medicine was given in 11 patients with CYP2C19-proven rapid metabolizers, silybin glucoside was given in 11 patients with CYP2C19-proven intermediate metabolizers, and silybin glucoside and phosphatidylcholine capsules were given in 10 patients with chronic metabolizers. Serum liver function tests and high-sensitivity C-reactive protein (hs-CRP) levels and serum interleukin-6 (IL-6) levels were detected routinely, and serum superoxide dismutase (SOD) and malondialdehyde (MDA) levels were detected by using visible spectrophotometry. Results By end of 6 week-treatment, the effective rates of antifungal treatment in group A, group B and group C were 78.1%, 75.0% and 84.4%(P＞0.05); the incidences of DILI in group A, B and C were 21.9%, 6.3% and 3.1%(P＜0.05); serum ALT, AST and bilirubin levels in group B and C were much lower than in group A, and serum ALT and AST level in patients with chronic metabolizers were much lower than in group B(P＜0.05); serum hs-CRP, IL-6 and MDA levels in group B and C were much lower than in group A, and serum MDA level in patients with chronic metabolizers was much lower than in group B (P＜0.05). Conclusion During voriconazole therapy in patients with FDL, a targeted preventive hepatoprotective treatment based on CYP2C19 gene metabolic type could precisely improve liver functions, which might finish anti-fungal treatment relatively safely.

Key words: Drug-induced liver injury, Fungal disease of the lung, Voriconazole, CYP2C19 gene polymorphism, Prophylaxis

程曦, 杨小康, 李尧, 董静, 宋海燕, 刘波, 陈照林. 伏立康唑导致的药物性肝损伤特征:基于CYP2C19基因代谢类型防治效果观察[J]. 实用肝脏病杂志, 2025, 28(6): 870-873.

Cheng Xi, Yang Xiaokang, Li Yao, et al. Prevention of drug-induced liver injury based on CYP2C19 gene polymorphism in patients with fungal disease of lung undergoing voriconazole therapy[J]. Journal of Practical Hepatology, 2025, 28(6): 870-873.

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