评估利福平耐药结核病新型和标准短期治疗方案的肝毒性：TB-TRUST 和 TB-TRUST -plus 试验的启示。

IF 4.8 2区医学 Q1 INFECTIOUS DISEASES

International Journal of Infectious Diseases Pub Date : 2024-09-04 DOI:10.1016/j.ijid.2024.107230

Lingyun Song , Yilin Zhang , Feng Sun , Yuanbo Lan , Jie Tong , Shijia Ge , Zhen Feng , Rong Li , Hongying Yu , Yang Li , Wenhong Zhang

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引用次数: 0

摘要

背景：为缩短耐利福平结核病（RR-TB）治疗时间所做的努力引起了人们对缩短治疗方案中肝脏毒性的担忧。我们对照世界卫生组织推荐的标准短期疗法，评估了两种新型疗法的肝毒性：TB-TRUST试验和TB-TRUST plus试验的参与者被分配到世界卫生组织推荐的较短疗程、基于左氧氟沙星的疗程或基于贝达喹啉的疗程中。第一个月每两周检测一次肝功能，之后每月检测一次，直至治疗结束。符合条件的患者必须至少接受过一次药物治疗，并至少接受过两次肝功能检测：在429名患者中，肝毒性最常见于WHO短效组（169人中占26.7%），而左氧氟沙星组（172人）和贝达喹啉组（88人）分别为4.7%和5.7%。WHO组、左氧氟沙星组和贝达喹啉组的ALT峰值中位数分别为1.67×ULN、0.82×ULN和0.88×ULN。WHO组药物性肝损伤的发生率（18.3%）明显高于左氧氟沙星组（3.5%）和贝达喹啉组（4.6%）。ALT明显升高的时间约为2.8个月，组间无差异：结论：与世界卫生组织的短效疗法相比，两种新型疗法的肝毒性较低。建议在 RR-TB 治疗中进行全程管理监测。

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Assessing hepatotoxicity in novel and standard short regimens for rifampicin-resistant tuberculosis: Insights from the TB-TRUST and TB-TRUST-plus trials

Objectives

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).

Methods

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.

Results

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.

Conclusions

Two novel regimens demonstrated lower hepatotoxicity compared to the WHO's shorter regimen. Entire course management monitoring is recommended in RR-TB treatment.

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来源期刊

International Journal of Infectious Diseases 医学-传染病学

CiteScore

18.90

自引率

2.40%

发文量

1020

审稿时长

30 days

期刊介绍： International Journal of Infectious Diseases (IJID) Publisher: International Society for Infectious Diseases Publication Frequency: Monthly Type: Peer-reviewed, Open Access Scope: Publishes original clinical and laboratory-based research. Reports clinical trials, reviews, and some case reports. Focuses on epidemiology, clinical diagnosis, treatment, and control of infectious diseases. Emphasizes diseases common in under-resourced countries.