Anti-tuberculosis drug–induced hepatotoxicity and associated risk factors among patients with pulmonary tuberculosis at a tertiary care hospital in Thailand

Abstract

Objectives

First-line anti-tuberculosis (TB) medications are effective for drug-susceptible TB but are commonly associated with hepatotoxicity, which can compromise treatment adherence and contribute to drug resistance. This study aimed to determine the frequency of anti-TB drug–induced hepatotoxicity and identify associated risk factors among patients at Chiang Mai University Hospital.

Methods

A retrospective cross-sectional study was conducted among patients with drug-susceptible pulmonary TB receiving standard treatment. Liver function tests were monitored biweekly during the first 2 months to detect hepatotoxicity. The risk factors evaluated included body mass index (BMI), age, alcohol use, N-acetyltransferase 2 (NAT2) acetylator status, and concomitant statin use. Adverse drug reactions were assessed by physicians using severity grading. Binary logistic regression and multivariate analysis were performed to identify independent predictors of hepatotoxicity. Adjusted odds ratios (ORs), 95% confidence intervals (CIs), and P-values were reported.

Results

The incidence of hepatotoxicity was 41.97%. The multivariate analysis showed significant associations between hepatotoxicity and the following: age >70 years (OR = 41.72, P = 0.001), underweight BMI (OR = 56.48, P = 0.001), current alcohol use (OR = 10.95, P = 0.001), and slow NAT2 acetylator status (OR = 78.18, P = 0.001).

Conclusions

Hepatotoxicity is a common complication of TB treatment. Older age, low BMI, alcohol use, slow NAT2 genotype, and statin co-administration significantly increase risk. Targeted monitoring and consideration of NAT2 genotyping in high-risk patients may help prevent treatment interruptions and improve clinical outcomes.