Analysis of predictive value of leukocytes telomere length of peripheral blood against drug-induced liver injury induced by tuberculosis drugs

Abstract

Abstract: Objective To analyse the value of leukocytes telomere length (LTL) of peripheral blood in predicting of drug-induced liver injury (DILI) by anti-tuberculosis drugs in patients with tuberculosis (TB). Methods A total of 78 patients with anti-TB drug induced DILI from October 2017 to November 2020 were included, and 100 patients with TB who were not diagnosed with DILI in the same period were selected. Univariate and multivariate analysis were performed to determine the independent predictors of DILI in TB patients, and ROC curve analysis was used to determine the cutoff point of independent predictors of DILI in TB patients, and the diagnostic sensitivity and specificity were calculated. Results According to the clinical data, there were 18 cases (23.1%), 56 cases (71.8%) and 72 cases (92.3%) of rash, fatigue and anorexia in TB patients with DILI (DILI group), compared with 7 cases (7.0%), 23 cases (23.0%) and 28 cases (28.0%) in TB patients without DILI (non-DILI group), with statistically significant (χ²=-9.382, -42.267 and -73.612, P<0.05). The alanine aminotransferase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), total bilirubin (Tbil), international normalized ratio (INR), LTL and model for end-stage liver disease (MELD) scores in DILI group were (232.8 ± 80.1) U/L, (134.8 ± 40.5) U/L, (172.4 ± 62.2) U/L, (2.4 ± 1.0) mg/L, (2.2 ± 0.8), (0.70 ± 0.31) and (17.3 ± 6.3) points, compared with (37.8 ± 8.4) U/L, (36.6 ± 8.5) U/L, (121.5 ± 38.5) U/L, (0.8 ± 0.3) mg/dL, (1.2 ± 0.3), (1.68 ± 0.61) and (8.2 ± 3.2) points in non-DILI group, with statistically significant (t=-60.128, -12.147, -8.136, -17.305, -14.736, 12.018 and -11.114, P<0.05). Multivariate logistic regression analysis was performed with whether TB patients had DILI (assigned value 0 = non-DILI, 1 = DILI) as the dependent variable and rash, fatigue, anorexia, ALT, AST, TBil, INR, LTL and MELD scores as the independent variables. The results showed that rash, fatigue, anorexia, ALT, AST, TBil, INR, LTL and MELD scores were independent predictors of DILI in patients with TB (P<0.05). Receiver operating characteristic (ROC) curve showed that the optimal cut-off point of LTL point in differentiating patients with and without DILI was 0.93, the sensitivity and specificity were 73.1% and 64.0%, respectively, while the area under the curve (AUC) values of AST and ALT were not statistically significant (P>0.05). Conclusion The abnormality of LTL in peripheral blood can reflect the liver injury caused by anti-TB drugs in patients with TB,which is a potential biomarker for early detection of DILI.

Key words: Drug-induced liver injury, Leukocytes telomere length, Tuberculosis, Multivariate logistic regression analysis

ZHANG Shu, YU Zhi-yang. Analysis of predictive value of leukocytes telomere length of peripheral blood against drug-induced liver injury induced by tuberculosis drugs[J]. Chinese Hepatolgy, 2022, 27(9): 1011-1014.

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