Department of Medicine, Division of Gastroenterology-Hepatology, Medstar Georgetown University Hospital, Washington, DC, USA.
Department of Medicine, General Internal Medicine, Medstar Georgetown University Hospital, Washington, DC, USA.
Expert Opin Drug Saf. 2024 Sep;23(9):1093-1107. doi: 10.1080/14740338.2024.2399074. Epub 2024 Sep 4.
Many of the first line medications for the treatment of active and latent M. tuberculosis are hepatoxic and cause a spectrum of anti-tuberculosis drug induced liver injury (ATLI), including acute liver failure (ALF). Despite advances in recognition of and prevention of ATLI, isoniazid remains one of the leading causes of DILI as well as drug-induced ALF.
A literature search of the incidence, risk factors, current societal guidelines, monitoring, and prophylactic medication usage in ATLI was performed using PubMed and institutional websites. Relevant articles from 1972 to 2024 were included in this review.
Current societal guidelines regarding ATLI monitoring are mixed, but many recommend liver enzyme testing of high-risk populations. We recommend liver test monitoring for all patients on multi-drug therapy as well as those on isoniazid therapy. Precision medicine practices, such as N-acetyltransferase-2 polymorphism genotyping, are thought to be beneficial in reducing the incidence of ATLI in high-risk populations. However, broader implementation is currently cost prohibitive. Hepatoprotective drugs are not currently recommended, although we do recognize their potential. In patients who develop ATLI but require ongoing anti-TB treatment, strategies to restart the same or less hepatotoxic regimens are currently being followed.
许多治疗活动性和潜伏性结核分枝杆菌的一线药物具有肝毒性，会引起一系列抗结核药物性肝损伤（ATLI），包括急性肝衰竭（ALF）。尽管在识别和预防 ATLI 方面取得了进展，但异烟肼仍然是导致 DILI 和药物性 ALF 的主要原因之一。
使用 PubMed 和机构网站对 ATLI 的发病率、风险因素、当前社会指南、监测和预防性药物使用进行了文献检索。本综述纳入了 1972 年至 2024 年的相关文章。
目前关于 ATLI 监测的社会指南存在差异，但许多指南建议对高危人群进行肝酶检测。我们建议对所有接受多药物治疗的患者以及接受异烟肼治疗的患者进行肝试验监测。人们认为，精准医学实践，如 N-乙酰转移酶-2 多态性基因分型，有助于降低高危人群中 ATLI 的发病率。然而，目前更广泛的实施是成本过高。目前不推荐使用肝保护药物，尽管我们确实认识到它们的潜力。对于发生 ATLI 但需要继续抗结核治疗的患者，目前正在采用重新启动相同或毒性较小的治疗方案的策略。
