Understanding antituberculosis drug-induced hepatotoxicity: Risk factors and effective management strategies in the...

Antituberculosis drug-induced hepatotoxicity (ATDIH) is a significant concern while managing pediatric tuberculosis. There is limited data on pediatric ATDIH, and much of the management practices are extrapolated from adult experiences. This article provides a comprehensive overview of the incidence, risk factors, clinical presentation, and management strategies for ATDIH in children. Pyrazinamide, isoniazid, and rifampicin are the most hepatotoxic first-line antituberculosis therapy (ATT). Though pyrazinamide has the highest potential for ATDIH, isoniazid is most frequently implicated. Hepatotoxicity typically manifests within the first 2-8 weeks of treatment, particularly during the intensive phase. Risk factors include younger age, female gender, malnutrition, hypoalbuminemia, and baseline liver dysfunction. Extra-pulmonary TB, particularly tuberculous meningitis, and concomitant hepatotoxic medications such as antiretro viral therapy or antiepileptic drugs further increase susceptibility. Genetic predisposition, including N-acetyltransferase 2 and cytochrome P4502E1 polymorphisms and specific HLA alleles also contribute to the increased risk. Clinically, ATDIH ranges from asymptomatic transaminase elevation to severe acute liver failure (ALF), necessitating prompt recognition and intervention. Diagnosis relies on the temporal association of liver injury with ATT initiation, supported by liver function tests, improvement upon ATT cessation, and recurrence upon reintroduction. Management involves discontinuing hepatotoxic drugs, initiating non-hepatotoxic regimens, and sequential reintroduction of ATT under close monitoring. For children with ALF, care in a tertiary center with liver transplantation expertise is essential. While pediatric ATDIH generally has favorable outcomes with timely intervention, delays can result in significant morbidity and mortality. Improved understanding of risk factors, vigilant monitoring protocols, and standardized pediatric management strategies are critical for optimizing outcomes in pediatric ATDIH.