Leukocyte telomere length as a diagnostic biomarker for anti-tuberculosis drug-induced liver injury

Abstract

AbstractDespite being relatively rare, anti-tuberculosis drug-induced liver injury (ATDILI) is a leading cause of acute liver failure and a major reason for treatment discontinuation, because of no specific and selective markers for ATDILI. Herein, this study aimed to investigate whether telomere length, a biological indicator of age-related diseases, is associated with ATDILI outcomes and could serve as an early ATDILI biomarker. Relative telomere length (RTL) in blood leukocyte of 100 age- and gender-matched healthy controls, 49 tuberculosis patients with ATDILI, and 53 tuberculosis patients with non-ATDILI was quantified using real-time polymerase chain reaction. Both tuberculosis patients with and without ATDILI had significantly shorter RTL than healthy controls. Compared with tuberculosis patients with non-ATDILI, RTL in those with ATDILI was significantly increased. Longer RTL was found to be significantly associated with increased susceptibility to ATDILI. Multivariate linear regression analysis showed that an increment in RTL was independently correlated with elevated values of aspartate aminotransferase and alanine aminotransferase assessed within 60 days after anti-tuberculosis treatment. Kaplan-Meier curve analysis demonstrated that longer RTL was associated with elevated rates of hepatotoxicity in tuberculosis patients. Receiver-operating characteristic curve analysis unveiled a diagnostic accuracy of RTL as a novel indicator for ATDILI progression (AUC = 0.73), which yielded more sensitive and specific values than traditional liver biomarkers including serum enzyme activities of aminotransferases measured within 7 days after treatment with anti-tuberculosis regimens. Collectively, aberrant RTL in blood leukocyte would reflect hepatotoxicity induced by anti-tuberculosis agents and might have a potential biomarker for early ATDILI progression.