Semwal P, Saini MK, Sarma MS. Understanding antituberculosis drug-induced hepatotoxicity: Risk factors and effective management strategies in the pediatric population. World J Clin Pediatr 2025; 14(2): 101875 [DOI: 10.5409/wjcp.v14.i2.101875]
Corresponding Author of This Article
Moinak Sen Sarma, DM, Additional Professor, Department of Pediatric Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Raebareli Road, Lucknow 226014, Uttar Pradesh, India. moinaksen@gmail.com
Research Domain of This Article
Pediatrics
Article-Type of This Article
Minireviews
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
World J Clin Pediatr. Jun 9, 2025; 14(2): 101875 Published online Jun 9, 2025. doi: 10.5409/wjcp.v14.i2.101875
Understanding antituberculosis drug-induced hepatotoxicity: Risk factors and effective management strategies in the pediatric population
Pooja Semwal, Manjit Kaur Saini, Moinak Sen Sarma
Pooja Semwal, Department of Pediatrics, Hind Institute of Medical Sciences, Lucknow, Lucknow 261303, Uttar Pradesh, India
Manjit Kaur Saini, Moinak Sen Sarma, Department of Pediatric Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow 226014, Uttar Pradesh, India
Author contributions: Semwal P and Saini MK drafted the manuscript; and all authors reviewed the manuscript; Sarma MS approved the final version of the manuscript.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Moinak Sen Sarma, DM, Additional Professor, Department of Pediatric Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Raebareli Road, Lucknow 226014, Uttar Pradesh, India. moinaksen@gmail.com
Received: September 29, 2024 Revised: January 6, 2025 Accepted: January 23, 2025 Published online: June 9, 2025 Processing time: 169 Days and 20.4 Hours
Abstract
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.
Core Tip: Antituberculosis therapy (ATT) causes hepatotoxicity as a major side effect. The withdrawal of ATT and modification of ATT remains the cornerstone for immediate management of ATT induced hepatotoxicity.
