Genetic and clinical risk factors for anti-tuberculosis drug-induced liver injury: insights from a prospective cohort study in central Ethiopia.

IF 3.6 2区医学 Q1 INFECTIOUS DISEASES

Infection Pub Date : 2025-09-04 DOI:10.1007/s15010-025-02632-7

Caroline Klindt, Andre Fuchs, Kristina Behnke, Carola Dröge, Kirsten Alexandra Eberhardt, Hans Christian Orth, Frieder Pfäfflin, Andreas Schönfeld, Tamara Nordmann, Million Getachew Mesfun, Verena Keitel, Tom Luedde, Tafese Beyene Tufa, Björn-Erik Ole Jensen, Torsten Feldt

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引用次数: 0

Abstract

Purpose: Drug-induced liver injury (DILI) is a relevant adverse event of tuberculosis treatment (TBT) especially in sub-Saharan Africa, but data remains limited. Genetic hepatic transport proteins polymorphisms (HTPP) are potential contributors. This study aimed to assess frequency and timing of DILI, identify risk factors, and explore the association of HTPP with DILI risk in Ethiopian TBT-patients.

Methods: In this prospective study, 424 confirmed tuberculosis patients in Ethiopian were recruited before initiation of TBT. Liver function tests were conducted during the first 8 weeks of treatment. Baseline evaluations included sociodemographic-, lifestyle- and clinical data including testing for viral co-infections, and HTPP as well as liver stiffness measurement by transient elastography (TE). Multivariable logistic regression, Cox proportional hazards models, and Fine and Gray competing risks analyses were employed for statistical analysis.

Results: Cumulative DILI incidence was 16.0% with 4.2% classified as severe occurring most commonly within the first two weeks. Urban residence (OR 2.00, 95% CI 1.03-3.84; HR 1.80, 95% CI 1.00-3.22) was associated with increased DILI risk. In the competing risks model, urban residence (sHR 6.26, p = 0.010) and pathologic TE (sHR 5.23, p = 0.005) predicted severe DILI. The investigated HTPPs were not significantly associated with DILI.

Conclusion: DILI is a common early complication of TBT in Ethiopian patients. Assessment of sociodemographic factors and TE before TBT may help identify high-risk individuals and offers a pragmatic approach for DILI management in resource-limited settings.

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抗结核药物性肝损伤的遗传和临床危险因素：来自埃塞俄比亚中部前瞻性队列研究的见解

目的：药物性肝损伤（DILI）是结核病治疗（TBT）的相关不良事件，特别是在撒哈拉以南非洲，但数据仍然有限。遗传肝转运蛋白多态性（HTPP）是潜在的致病因素。本研究旨在评估埃塞俄比亚tbt患者DILI的频率和时间，确定危险因素，并探讨HTPP与DILI风险的关系。方法：在这项前瞻性研究中，在开始TBT之前招募了424名埃塞俄比亚确诊结核病患者。在治疗的前8周进行肝功能检查。基线评估包括社会人口学、生活方式和临床数据，包括病毒合并感染检测、HTPP以及通过瞬时弹性成像（TE）测量肝脏硬度。采用多变量logistic回归、Cox比例风险模型和Fine and Gray竞争风险分析进行统计分析。结果：DILI的累积发生率为16.0%，其中4.2%为重度，最常见于前两周。城市居住（OR 2.00, 95% CI 1.03-3.84; HR 1.80, 95% CI 1.00-3.22）与DILI风险增加相关。在竞争风险模型中，城市居住（sHR 6.26, p = 0.010）和病理性TE （sHR 5.23, p = 0.005）预测严重DILI。所研究的HTPPs与DILI无显著相关性。结论：DILI是埃塞俄比亚TBT患者常见的早期并发症。在TBT之前评估社会人口因素和TE可能有助于识别高风险个体，并为资源有限的环境中DILI的管理提供实用的方法。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Infection 医学-传染病学

CiteScore

12.50

自引率

1.30%

发文量

224

审稿时长

6-12 weeks

期刊介绍： Infection is a journal dedicated to serving as a global forum for the presentation and discussion of clinically relevant information on infectious diseases. Its primary goal is to engage readers and contributors from various regions around the world in the exchange of knowledge about the etiology, pathogenesis, diagnosis, and treatment of infectious diseases, both in outpatient and inpatient settings. The journal covers a wide range of topics, including: Etiology: The study of the causes of infectious diseases. Pathogenesis: The process by which an infectious agent causes disease. Diagnosis: The methods and techniques used to identify infectious diseases. Treatment: The medical interventions and strategies employed to treat infectious diseases. Public Health: Issues of local, regional, or international significance related to infectious diseases, including prevention, control, and management strategies. Hospital Epidemiology: The study of the spread of infectious diseases within healthcare settings and the measures to prevent nosocomial infections. In addition to these, Infection also includes a specialized "Images" section, which focuses on high-quality visual content, such as images, photographs, and microscopic slides, accompanied by brief abstracts. This section is designed to highlight the clinical and diagnostic value of visual aids in the field of infectious diseases, as many conditions present with characteristic clinical signs that can be diagnosed through inspection, and imaging and microscopy are crucial for accurate diagnosis. The journal's comprehensive approach ensures that it remains a valuable resource for healthcare professionals and researchers in the field of infectious diseases.