Changing Trajectories of Alanine Aminotransferase and Risk of Antituberculosis Drug-Induced Liver Injury in Chinese Patients: A Cohort Study

J Clin Pharmacol. 2024 Mar 4. doi: 10.1002/jcph.2422. Online ahead of print.

Abstract

Antituberculosis drug-induced liver injury (ATLI) is a major adverse effect during antituberculosis treatment. Early detection or prediction is essential to prevent ATLI in antituberculosis treatment patients. The purpose of this work is to explore the relationship between alanine aminotransferase (ALT) trajectories within 15 days of initial treatment and the risk of ATLI. Based on a historical cohort of patients hospitalized for antituberculosis treatment and group-based trajectory modeling analysis, ALT trajectories within 15 days of initial treatment were determined. Conditional logistic regression model was used to estimate the association between different ALT trajectories and the risk of ATLI, and the corresponding odds ratios (ORs) and their 95% confidence intervals (CIs) were calculated with covariates. Based on the ALT levels within 15 days of initial treatment, a total of 853 patients were divided into four ALT trajectories. The incidence of ATLI significantly increased with the increase of ALT trajectories (2.33%, 4.38%, 5.90%, and 2.44%, respectively). Compared with trajectory 1, the adjusted OR for ATLI in trajectory 2, trajectory 3, and trajectory 4 were 2.448 (95% CI: 0.302-19.856, P = 0.402), 5.373 (95% CI: 0.636-45.411, P = 0.123), 11.010 (95% CI: 0.720-168.330, P = 0.085), respectively, and there was an increasing trend of ATLI risk (Ptrend = 0.015). Different ALT trajectories within 15 days of initial treatment were associated with different risk of ATLI, and it is necessary to pay attention to the ALT trajectory within 15 days of initial treatment to predict the occurrence of ATLI.

Keywords: alanine aminotransferase; antituberculosis treatment; cohort study; drug-induced liver injury; group-based trajectory modeling analysis.