目的:异烟肼是肝损伤的主要原因,但目前尚不清楚有多少病例报告或有多少临床医生和患者遵守美国胸科学会(ATS)指南。我们收集了异烟肼肝毒性病例的数据,并评估了对ATS指南的依从性,并向疾病控制中心(CDC)的异烟肼严重不良事件计划报告。
方法:我们分析了认为明确的药物性肝损伤网络(DILIN)病例,极有可能,或可能从2004年到2013年的异烟肼损伤。我们根据ATS标准和严重程度指数评分评估了异烟肼停药的延迟和肝毒性的严重程度。我们通过根据年龄匹配病例来检查向CDC的报告,延迟,指示,报告期,和合并症。
结果:异烟肼是DILIN中第二常见的药物,69例;其中60例符合纳入标准。病例的中位年龄为49岁(范围,4-68y),70%是女性,97%有潜伏性肺结核,62%住院。患者停止服用异烟肼的中位数为9天(范围,0-99天)。33例(55%)在满足ATS停用标准后继续服用异烟肼超过7天。24例(40%)在满足停止标准后继续使用异烟肼超过14天。延迟停止与更严重的损伤相关(P<0.05)。在13例死亡或接受肝移植的患者中,9(70%)在满足停止标准后继续服用异烟肼超过7天。在符合向CDC报告的25例异烟肼肝毒性病例中,仅报告了1例。
结论:对ATS指南的依从性差在肝毒性病例中是常见的,并且与更严重的结局相关,包括住院。死亡,和肝移植。异烟肼仍然是美国DILI的主要原因,其肝毒性报道明显不足。
OBJECTIVE: Isoniazid is a leading cause of liver injury but it is not clear how many cases are reported or how many clinicians and patients adhere to American Thoracic Society (ATS)
guidelines. We collected data on cases of isoniazid hepatotoxicity and assessed adherence to ATS
guidelines and reports to the Centers for Disease Control\'s (CDC) isoniazid severe adverse events program.
METHODS: We analyzed Drug-Induced Liver Injury Network (DILIN) cases considered definite, highly likely, or probable for isoniazid injury from 2004 through 2013. We assessed the delays in isoniazid discontinuance according to ATS criteria and hepatotoxicity severity by Severity Index Score. We checked reporting to the CDC by matching cases based on age, latency, indication, reporting period, and comorbidities.
RESULTS: Isoniazid was the second most commonly reported agent in the DILIN, with 69 cases; 60 of these met inclusion criteria. The median age of cases was 49 years (range, 4-68 y), 70% were female, 97% had latent tuberculosis, and 62% were hospitalized. Patients took a median of 9 days to stop taking isoniazid (range, 0-99 days). Thirty-three cases (55%) continued taking isoniazid for more than 7 days after the ATS criteria for stopping were met. Twenty-four cases (40%) continued isoniazid for more than 14 days after meeting criteria for stopping. A delay in stopping was associated with more severe injury (P < .05). Of 13 patients who died or underwent liver transplantation, 9 (70%) continued taking isoniazid for more than 7 days after meeting criteria for stopping. Only 1 of 25 cases of isoniazid hepatotoxicity eligible for reporting to the CDC was reported.
CONCLUSIONS: Poor adherence to ATS
guidelines is common in cases of hepatotoxicity and is associated with more severe outcomes including hospitalization, death, and liver transplantation. Isoniazid continues to be a leading cause of DILI in the United States, and its hepatotoxicity is under-reported significantly.