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. 2023 Aug 7;10(8):ofad422.
doi: 10.1093/ofid/ofad422. eCollection 2023 Aug.

Metabolic Disorders Are Associated With Drug-Induced Liver Injury During Antituberculosis Treatment: A Multicenter Prospective Observational Cohort Study in Korea

Jihye Lim  1 , Ju Sang Kim  2 , Hyung Woo Kim  2 , Yong Hyun Kim  3 , Sung Soo Jung  4 , Jin Woo Kim  5 , Jee Youn Oh  6 , Heayon Lee  7 , Sung Kyoung Kim  8 , Sun-Hyung Kim  9 , Jiwon Lyu  10 , Yousang Ko  11 , Sun Jung Kwon  12 , Yun-Jeong Jeong  13 , Do Jin Kim  14 , Hyeon-Kyoung Koo  15 , Yangjin Jegal  16 , Sun Young Kyung  17 , Tai Joon An  18 , Jinsoo Min  19
Affiliations

Metabolic Disorders Are Associated With Drug-Induced Liver Injury During Antituberculosis Treatment: A Multicenter Prospective Observational Cohort Study in Korea

Jihye Lim et al. Open Forum Infect Dis. .

Abstract

Background: Drug-induced liver injury (DILI) may lead to the discontinuation of antituberculosis (anti-TB) treatment (ATT). Some studies have suggested that metabolic disorders increase the risk of DILI during ATT. This study aimed to identify risk factors for DILI, particularly metabolic disorders, during ATT.

Methods: A multicenter prospective observational cohort study to evaluate adverse events during ATT was conducted in Korea from 2019 to 2021. Drug-susceptible patients with TB who had been treated with standard ATT for 6 months were included. The patients were divided into 2 groups depending on the presence of 1 or more metabolic conditions, such as insulin resistance, hypertension, obesity, and dyslipidemia. We monitored ATT-related adverse events, including DILI, and treatment outcomes. The incidence of DILI was compared between individuals with and without metabolic disorders, and related factors were evaluated.

Results: Of 684 patients, 52 (7.6%) experienced DILI, and 92.9% of them had metabolic disorders. In the multivariable analyses, underlying metabolic disorders (adjusted hazard ratio [aHR], 2.85; 95% CI, 1.01-8.07) and serum albumin <3.5 g/dL (aHR, 2.26; 95% CI, 1.29-3.96) were risk factors for DILI during ATT. In the 1-month landmark analyses, metabolic disorders were linked to an elevated risk of DILI, especially significant alanine aminotransferase elevation. The treatment outcome was not affected by the presence of metabolic disorders.

Conclusions: Patients with metabolic disorders have an increased risk of ATT-induced liver injury compared with controls. The presence of metabolic disorders and hypoalbuminemia adversely affects the liver in patients with ATT.

Keywords: antitubercular agents; chemical and drug-induced liver injury; metabolic syndrome; risk factors; tuberculosis‌.

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Figures

Figure 1.
Figure 1.
Flowchart of patient enrollment. Abbreviations: ATT, antituberculosis treatment; TB, tuberculosis.
Figure 2.
Figure 2.
Cumulative risks of drug-induced liver injury during antituberculosis treatment according to the presence of metabolic disorders. A, Drug-induced liver injury. B, Clinically significant alanine aminotransferase elevation. C, Clinically significant aspartate aminotransferase elevation. D, Clinically significant total bilirubin elevation. Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase.
Figure 3.
Figure 3.
One-month landmark analysis for cumulative risks of drug-induced liver injury during antituberculosis treatment according to the presence of metabolic disorders. A, Drug-induced liver injury. B, Clinically significant alanine aminotransferase elevation. C, Clinically significant aspartate aminotransferase elevation. D, Clinically significant total bilirubin elevation. Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase.
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