Assessing hepatotoxicity in novel and standard short regimens for rifampicin-resistant tuberculosis: Insights from the TB-TRUST and TB-TRUST-plus trials
Lingyun Song , Yilin Zhang , Feng Sun , Yuanbo Lan , Jie Tong , Shijia Ge , Zhen Feng , Rong Li , Hongying Yu , Yang Li , Wenhong Zhang
{"title":"Assessing hepatotoxicity in novel and standard short regimens for rifampicin-resistant tuberculosis: Insights from the TB-TRUST and TB-TRUST-plus trials","authors":"Lingyun Song , Yilin Zhang , Feng Sun , Yuanbo Lan , Jie Tong , Shijia Ge , Zhen Feng , Rong Li , Hongying Yu , Yang Li , Wenhong Zhang","doi":"10.1016/j.ijid.2024.107230","DOIUrl":null,"url":null,"abstract":"<div><h3>Objectives</h3><div>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).</div></div><div><h3>Methods</h3><div>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.</div></div><div><h3>Results</h3><div>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.</div></div><div><h3>Conclusions</h3><div>Two novel regimens demonstrated lower hepatotoxicity compared to the WHO's shorter regimen. Entire course management monitoring is recommended in RR-TB treatment.</div></div>","PeriodicalId":14006,"journal":{"name":"International Journal of Infectious Diseases","volume":"148 ","pages":"Article 107230"},"PeriodicalIF":4.8000,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"International Journal of Infectious Diseases","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1201971224003011","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"INFECTIOUS DISEASES","Score":null,"Total":0}
引用次数: 0
Abstract
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.
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.