Antitubercular drug-induced liver injury (ATDILI) poses a significant obstacle to successful tuberculosis treatment, including for tuberculous lymphadenitis. Its global incidence varies considerably, typically ranging from 2% to 30%, influenced by factors like patient demographics, co-morbidities, and geographical context. Despite some findings suggesting potentially lower rates in tuberculous lymphadenitis, the inherent hepatotoxic nature of standard anti-TB drugs means the risk remains clinically relevant. Key risk factors for ATDILI encompass older age, female gender, pre-existing liver conditions, HIV co-infection, malnutrition, alcoholism, and genetic polymorphisms, particularly in N-acetyltransferase 2 which affects isoniazid metabolism. The mechanisms of injury are drug-specific: isoniazid primarily causes hepatocellular damage via oxidative stress from toxic metabolites, while rifampicin induces cholestasis and endoplasmic reticulum stress, and pyrazinamide is linked to mitochondrial dysfunction. Management involves prompt withdrawal of antitubercular therapy when liver enzyme thresholds are exceeded, followed by careful reintroduction. Challenges are amplified in resource-limited settings due to higher prevalence of risk factors and limited access to consistent monitoring and sophisticated diagnostics. Promising advancements include safer regimens like the 3-month once-weekly isoniazid-rifapentine (3HP) for latent TB, which significantly reduces hepatotoxicity. The development of shorter active TB regimens and novel anti-TB drugs with improved safety profiles further aims to enhance treatment adherence and reduce ATDILI incidence, ultimately improving patient outcomes globally.
Skuhala et al. (2026) studied this question.