Incidence and associated risk factors of antituberculosis drug induced hepatotoxicity among TB patients

Background Tuberculosis (TB) is a global health challenge. Use of anti-TB drugs to treat TB is associated with high prevalence of side effects and unpredictable clinical hepatotoxicity that include anti-TB drug induced liver injury (ATDILI). The aim of this study was to determine the incidence and associated clinical risk factors of ATDILI among South African patients with TB infections. Methods This was an exploratory, mixed prospective and retrospective case control study of patients with TB infections receiving drug sensitive and drug resistant treatment regimens. The retrospective and prospective studies were done from January 2021 to June 2024, involving a total of 616 patients with TB infections from whom 13 had ATDILI. From the retrospective and prospective cohorts, we extracted 13 ATDILI cases and 276 controls. Additionally, 44 extreme ATDILI cases were directly recruited from the hospital to enrich the number of cases in the study. All participants provided informed consent and had available DNA samples for genetic analysis. Results In the studied cohorts, the incidence of ATDILI was 2.1% (13/616). The ATDILI cases and controls consisted of 215 (64.56%) male patients; 57 patients were diagnosed with hepatotoxicity, 44 from the hospitalized cohort,12 from the retrospective cohort and 1 patient from the prospective cohort. The median time from the initiation of treatment to the onset of hepatotoxicity was approximately 30 days. Univariate logistic regression revealed significant differences (p < 0.05) in gender (p = 0.001), HIV status (p = 0.004), BMI (p = 0.036), Hypertension (p = 0.047) smoking (p = 0.010), and alcohol consumption (p = 0.003) in relation to ATDILI. Multivariate analysis further demonstrated that female gender (p = 0.041) had a cumulative risk factor for ATDILI. Conclusions The incidence of ATDILI of 2.1% is on the lower end of the reported literature values of 5–35% indicative of potentially less rigorous ATDILI phenotype assignment in previous studies reporting much higher values. Female gender, HIV status, BMI, Hypertension, smoking, and alcohol consumption were identified as risk factors associated with ATDILI. Among these, the cumulative effect of gender significantly increased the risk of developing ATDILI. The DNA from the case and control samples is undergoing further genomic analysis in search of potential genetic biomarkers for ATDILI.