目的:引起特异性药物性肝损伤(DILI)的抗癫痫药物是暴露于这些药物的个体发病和死亡的重要原因。临床和人口统计学特征,肝损伤模式,结果,和负责肝毒性的药物尚未被彻底研究。我们调查了大量DILI注册患者的上述特征。
方法:从1998年至2021年的大型单中心DILI注册表中研究了患有抗癫痫发作的DILI患者。DILI由国际工作组标准定义,至少与RUCAM有可能的关系。研究了免疫过敏特征和器官特异性对结果的贡献。
结果:在1067例特异性DILI患者中,抗癫痫药物占133例(12.5%)。与其他代理商相比,抗癫痫DILI患者年龄较小(31岁vs41岁;p=0.31),更常见的是女性(52%vs46%;p=0.19),并且黄疸的频率较低(41%vs59%,p=0.001),MELD评分(14.5vs16.5;p=0.02)和死亡率(9.8%vs15.7%,p=0.03)。抗癫痫DILI表现出更高的过敏性皮疹频率(75%vs22%,p<0.001),包括连衣裙(51%对13%,p<0.001)和SJS/TEN(19%vs1%,p<0.001)。共有18种不同的抗癫痫药负责DILI,主要由卡马西平(n=36),苯妥英(n=71),苯巴比妥(n=8)和丙戊酸(n=14)占病例的89%和13例死亡的85%。
结论:抗癫痫DILI主要由第一代药物引起。较新的代理商占病例的<10%。超敏反应是最常见的表型表现。抗癫痫DILI的严重程度和死亡率均较低。
Anti-seizure drugs that cause
idiosyncratic drug-induced liver injury (DILI) are an important cause of morbidity and mortality in individuals exposed to these drugs. The clinical and demographic characteristics, the liver injury pattern, the outcome, and the agents responsible for hepatotoxicity have not been thoroughly studied. We investigated the aforementioned characteristics in a large cohort of DILI registry patients.
Patients with anti-seizure DILI were studied from a large single-center DILI registry between 1998 and 2021. DILI was defined by international working group criteria with at least a probable relation with RUCAM. Immunoallergic features and organ-specific contribution to outcome were investigated.
Anti-seizure drugs accounted for 133 patients (12.5%) among 1067 patients with
idiosyncratic DILI. Compared to other agents, patients with anti-seizure DILI were younger (31 vs 41 years; p = 0.31), were more often females (52% vs 46%; p = 0.19) and had a lower frequency of jaundice (41% vs 59%, p = 0.001), MELD score (14.5 vs 16.5; p = 0.02) and mortality (9.8% vs 15.7%, p = 0.03). Anti-seizure DILI exhibited a greater frequency of hypersensitivity skin rashes (75% vs 22%, p < 0.001), including DRESS (51% vs 13%, p < 0.001) and SJS/TEN (19% vs1%, p < 0.001). A total of 18 different anti-seizure agents were responsible for DILI, largely contributed by carbamazepine (n = 36), phenytoin (n = 71), phenobarbitone (n = 8) and valproate (n = 14) which accounted for 89% of cases and 85% of 13 deaths.
Anti-seizure DILI are caused predominantly by first generation drugs. Newer agents account for < 10% of cases. Hypersensitivity reaction is the most common phenotypic presentation. Both severity and mortality are lower with anti-seizure DILI.