他汀类药物对活动性肺结核患者抗结核药物性肝损伤风险的影响：一项队列研究。

The effect of statins on the risk of anti-tuberculosis drug-induced liver injury among patients with active tuberculosis: A cohort study.

机构信息

Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Institute of Epidemiology & Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan.

Institute of Epidemiology & Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan; Department of Nuclear Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.

出版信息

J Microbiol Immunol Infect. 2024 Jun;57(3):498-508. doi: 10.1016/j.jmii.2024.04.002. Epub 2024 Apr 8.

DOI:10.1016/j.jmii.2024.04.002

PMID:38632021

Abstract

BACKGROUND

Tuberculosis (TB) remains prevalent worldwide, and anti-TB drugs are associated with drug-induced liver injury (DILI). Statins have pleiotropic effects which may decrease inflammation and achieve immunomodulation. However, few studies have investigated the pleiotropic effects of statins on the risk of DILI. The purpose of this study was to investigate whether statins prevent anti-tuberculosis DILI among active TB patients on standard anti-TB drug therapy.

METHODS

We conducted a hospital-based retrospective cohort study using claims data from the Integrated Medical Database of National Taiwan University Hospital (NTUH-iMD). Patients with a positive TB culture were included. The use of statins was defined as a daily equivalent dose >0.5 mg of pitavastatin. Deterioration in liver function was evaluated according to elevated liver enzyme levels. The primary and secondary endpoints were the DILI and the severe DILI. The prognostic value of statins was evaluated by Kaplan-Meier analysis, and Cox proportional hazards models.

RESULTS

A total of 1312 patients with a diagnosis of TB and receiving anti-TB treatment were included. During the study period, 193 patients had the DILI and 140 patients had the severe DILI. Kaplan-Meier analysis showed a significant difference between the usual statin users and controls in the DILI. In multivariable Cox proportional hazards analysis, statins showed a protective effect against the primary and secondary endpoints. In addition, the protective effect of statins showed a dose-response relationship against the DILI.

CONCLUSION

Statin treatment had a protective effect against the risk of anti-TB DILI with a positive dose-response relationship.

摘要

背景

结核病（TB）在全球仍然普遍存在，抗结核药物与药物性肝损伤（DILI）有关。他汀类药物具有多种作用，可能会减轻炎症并实现免疫调节。但是，很少有研究调查他汀类药物对 DILI 风险的多效作用。本研究旨在探讨他汀类药物是否可以预防活动性结核病患者在接受标准抗结核药物治疗时发生抗结核 DILI。

方法

我们进行了一项基于医院的回顾性队列研究，使用来自台湾大学医院综合医疗数据库（NTUH-iMD）的索赔数据。纳入结核培养阳性的患者。他汀类药物的使用定义为每天等效剂量> 0.5mg 的匹伐他汀。根据肝酶水平升高来评估肝功能恶化情况。主要和次要终点分别为 DILI 和严重 DILI。通过 Kaplan-Meier 分析和 Cox 比例风险模型评估他汀类药物的预后价值。

结果

共纳入 1312 例诊断为结核病并接受抗结核治疗的患者。在研究期间，193 例患者发生了 DILI，140 例患者发生了严重 DILI。Kaplan-Meier 分析显示，通常使用他汀类药物的患者与对照组之间在 DILI 方面存在显著差异。多变量 Cox 比例风险分析表明，他汀类药物对主要和次要终点具有保护作用。此外，他汀类药物的保护作用与 DILI 呈剂量反应关系。