Department of Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, National Medical Center for Infectious Diseases, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China.
Department of Tuberculosis, Affiliated Hospital of Zunyi Medical University, Zunyi, China.
Int J Infect Dis. 2024 Nov;148:107230. doi: 10.1016/j.ijid.2024.107230. Epub 2024 Sep 4.
Efforts to shorten rifampicin-resistant tuberculosis (RR-TB) treatment have led to concerns about hepatotoxicity in shorter regimens. We evaluated hepatotoxicity in two novel regimens against the standard shorter regimen recommended by the World Health Organization (WHO).
Participants from the TB-TRUST and TB-TRUST plus trials were assigned to the WHO shorter regimen, a levofloxacin (Lfx)-based regimen, or a bedaquiline (Bdq)-based regimen. Liver function was tested bi-weekly in the first month, then monthly until treatment ended. Eligibility required receiving at least one drug dose and undergoing at least two liver function tests.
Of 429 patients, hepatotoxicity was most prevalent in the WHO shorter group (26.7% of 169), compared to 4.7% in the Lfx group (172 patients), and 5.7% in the Bdq group (88 patients). The median peak alanine aminotransferase levels were 1.67 × upper limit of normal (ULN) for WHO, 0.82 × ULN for Lfx, and 0.88 × ULN for Bdq groups. The incidence of drug-induced liver injury was significantly higher in the WHO group (18.3%) than in the Lfx (3.5%) and Bdq (4.6%) groups. The time to significant alanine aminotransferase elevation was about 2.8 months, with no differences between groups.
Two novel regimens demonstrated lower hepatotoxicity compared to the WHO's shorter regimen. Entire course management monitoring is recommended in RR-TB treatment.
缩短利福平耐药结核病（RR-TB）治疗的努力导致了对较短方案中肝毒性的担忧。我们评估了两种新方案与世界卫生组织（WHO）推荐的较短标准方案相比的肝毒性。
来自 TB-TRUST 和 TB-TRUST plus 试验的参与者被分配到 WHO 较短的方案、左氧氟沙星（Lfx）为基础的方案或贝达喹啉（Bdq）为基础的方案。在第一个月每两周测试一次肝功能，然后每月测试一次，直到治疗结束。合格标准为至少接受一种药物剂量并进行至少两次肝功能测试。
在 429 名患者中，肝毒性在 WHO 较短组（169 名患者中的 26.7%）最为常见，Lfx 组（172 名患者）为 4.7%，Bdq 组（88 名患者）为 5.7%。WHO 组丙氨酸氨基转移酶峰值中位数为正常上限（ULN）的 1.67 倍，Lfx 组为 0.82 倍，Bdq 组为 0.88 倍。WHO 组药物性肝损伤的发生率（18.3%）明显高于 Lfx 组（3.5%）和 Bdq 组（4.6%）。丙氨酸氨基转移酶显著升高的时间约为 2.8 个月，各组之间无差异。
与 WHO 的较短方案相比，两种新方案显示出较低的肝毒性。在 RR-TB 治疗中推荐进行整个疗程的管理监测。
