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

Chun-Kai Huang; Jei-Yie Huang; Chin-Hao Chang; Shang-Jie Tsai; Chin-Chung Shu; Hao-Chien Wang; Kuo-Liong Chien

doi:10.1016/j.jmii.2024.04.002

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

J Microbiol Immunol Infect. 2024 Apr 8:S1684-1182(24)00069-0. doi: 10.1016/j.jmii.2024.04.002. Online ahead of print.

Authors

Chun-Kai Huang¹, Jei-Yie Huang², Chin-Hao Chang³, Shang-Jie Tsai³, Chin-Chung Shu⁴, Hao-Chien Wang⁵, Kuo-Liong Chien⁶

Affiliations

¹ Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Institute of Epidemiology & Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan. Electronic address: ckhuang226@gmail.com.
² 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.
³ Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan.
⁴ Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan. Electronic address: ccshu@ntu.edu.tw.
⁵ Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; The National Taiwan University Cancer Center, Taipei, Taiwan.
⁶ Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Institute of Epidemiology & Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan.

PMID: 38632021
DOI: 10.1016/j.jmii.2024.04.002

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.

Keywords: Anti-tuberculosis drug; Drug-induced liver injury; Statin; Tuberculosis.