Time of Liver Function Abnormal Identification on Prediction of the Risk of Anti-tuberculosis-induced Liver Injury

BACKGROUND AND AIMS: Anti-tuberculosis (anti-TB) drug-induced liver injury (AT-DILI) is the most common side effect in patients who received anti-TB therapy. AT-DILI management includes monitoring liver function until symptoms arise in patients without high-risk factors for liver damage. The present study aimed to investigate the effect of liver function test (LFT) abnormal identification on the risk of DILI, including liver failure and anti-TB drug resistance in patients without high-risk factors. METHODS: A total of 399 patients without high-risk factors for liver damage at baseline and who experienced LFT abnormal during the 6 months of first-line anti-TB treatment were enrolled. The Roussel Uclaf Causal Relationship Assessment Method (RUCAM, 2016) was applied in suspected DILI. The correlations between the time of LFT abnormal identification and DILI, liver failure, and anti-TB drug resistance were analyzed by smooth curve fitting and multivariable logistic regression models. RESULTS: Among all study patients, 131 met the criteria for DILI with a mean RUCAM causality score of 8.86±0.63. 26/131 and 105/131 were in the probable grading and highly probable grading, respectively. The time of abnormal LFT identification was an independent predictor of DILI, liver failure, and anti-TB drug resistance in the crude model and after adjusting for other risk patient factors. The time of abnormal LFT identification was positively correlated with DILI, liver failure, and anti-TB drug resistance. The late identification group (>8 weeks) had the highest risk of DILI, followed by liver failure compared with the other two groups. CONCLUSIONS: The time to identification of LFT was positively correlated with DILI, liver failure, and anti-TB drug resistance. The risk of DILI and liver failure was significantly increased in the late identification group with abnormal LFT identified after 8 weeks compared with 4 and 8 weeks. Early monitoring of LFT is recommended for patients without the high-risk factor of DILI after anti-TB treatment is initiated.