Mitochondrial DNA content as a diagnostic marker for antituberculosis drug-induced liver injury

Objectives: This study aimed to investigate whether mitochondrial DNA (mtDNA) content, an index of mitochondrial dysfunction, was associated with clinical parameters indicating anti-tuberculosis (TB) drug -induced liver injury (ATDILI) in TB patients and could emerge as an ATDILI biomarker.Methods: Leukocyte mtDNA content in 102 TB patients (49 ATDILI cases and 53 non-ATDILI cases) and 100 age-matched healthy controls was measured using real-time polymerase chain reaction. Results: Compared with healthy controls, both TB patients with and without ATDILI had significantly decreased mtDNA content. Compared with the patients without ATDILI, mtDNA content was significantly increased in those with ATDILI. Higher mtDNA content was observed to be independently associated with increased susceptibility to ATDILI. Increased mtDNA content measured within 1-7 days of treatment was independently associated with elevated levels of serum aminotransferases assessed within 8-60 days of treatment. After initiating treatment within 1-7 days, mtDNA content was detected to be more sensitive and selective for differentiating TB patients with ATDILI from those without ATDILI than serum amino-transferases. Kaplan-Meier analysis revealed a significant correlation between elevated mtDNA content and increased rate of ATDILI occurrence in TB patients, attested by Cox regression analysis, adjusting for confounders.Conclusion: Changes in leukocyte mtDNA content would reflect ATDILI progression and could be used as a potential stratification tool for identifying TB patients at risk of ATDILI.(c) 2022 The Authors. Published by Elsevier Ltd on behalf of International Society for Infectious Diseases. This is an open access article under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ )

Automated summary

This study found that mitochondrial DNA (mtDNA) content was associated with anti-tuberculosis drug-induced liver injury (ATDILI) and could potentially serve as a biomarker for ATDILI. TB patients with ATDILI had significantly increased mtDNA content compared to those without ATDILI, and higher mtDNA content was independently associated with an increased risk of ATDILI. Measurement of mtDNA content within 1-7 days of treatment was more sensitive and selective than serum aminotransferases in differentiating TB patients with and without ATDILI.