Incidence and Temporal Trend of Antituberculosis Drug-Induced Liver Injury: A Systematic Review and Meta-Analysis

Abstract

Background and Aim. Antituberculosis (anti-TB) drug-induced liver injury (ATLI) is a common and serious adverse drug reaction of tuberculosis treatment, and the incidence of ATLI has been reported to vary from 2.0% to 28.0%. This study aims to estimate the incidence of ATLI in patients who receive anti-TB treatment and describe its temporal trend in the world. Methods. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses standards were followed, and the protocol was registered in PROSPERO (CRD42020200077). Five electronic databases were searched to identify eligible studies published between 1990 and 2022. Search terms included anti-TB treatment and drug-induced liver injury. Studies that reported the incidence of ATLI or provided sufficient data to calculate the incidence of ATLI were included, and duplicate studies were excluded. Meta-analysis was conducted on the basis of logit-transformed metrics for the incidence of ATLI with 95% confidence intervals (CIs), followed by a predefined subgroup meta-analysis. Temporal trend analyses were performed to describe the change in pooled incidence over time. A random effects metaregression was conducted to explore the source of heterogeneity. All statistical analyses were carried out using R 4.0.1. Results. A total of 160 studies from 156 records with 116147 patients were included in the meta-analysis. Based on the random effects model, the pooled incidence of ATLI was 11.50% (95% CI: 10.10%–12.97%) and showed an upward trend over time ( $P<0.001$ ). Patients who received first-line anti-TB drugs, patients in South America, and patients with hepatitis B and C virus coinfection had a higher incidence of ATLI (13.66%, 18.16%, and 39.19%, respectively). Sensitivity analyses also confirmed this robust incidence after the exclusion of some studies. The metaregression showed that different anti-TB regimens and geographical regions were important explanatory factors of the heterogeneity between studies. Conclusions. The present systematic review provided a basis for estimating the incidence of ATLI worldwide, which varied among patients with different anti-TB regimens in different geographical regions and with different coinfections and had an upward trend. Regular liver function monitoring is imperative for patient safety during the anti-TB treatment course.