Syifa Mustika, Lia Susanti

Liver Injury Associated with Antituberculosis Medications

Introduction

Liver injury associated with antituberculosis medications. Evaluate antituberculosis drug-induced liver injury (DILI), its causes, diagnosis, and management. Learn about risk factors, monitoring, and tailored approaches for safe tuberculosis treatment.

Abstract

Tuberculosis remains a major global health concern, with a sharp increase in new cases in 2022, exceeding the prevalence before the coronavirus disease 2019 (COVID-19) pandemic. Conventional antituberculosis therapy, comprising a combination of first-line medications, is essential for controlling tuberculosis. However, more than 7% of patients undergoing treatment may develop drug-induced liver injury (DILI), mainly from isoniazid and rifampicin. This literature review aimed to evaluate DILI in tuberculosis, focusing on its causes, diagnosis, and management. Several factors, including age, sex, genetic predisposition, and pre-existing liver conditions, affect the occurrence of antituberculosis DILI. Advanced age and being female are significant risk factors for severe liver injury. Diagnosing DILI requires careful differentiation from other hepatic disorders, as its clinical presentation may include symptoms such as jaundice, abdominal pain, and elevated liver enzyme levels. Early detection relies heavily on liver function tests and clinical assessments. Managing DILI involves promptly discontinuing the offending drug, closely monitoring the patient, and gradually reintroducing medications, prioritizing less hepatotoxic options, such as rifampicin. Hepatoprotective agents and alternative drug regimens, particularly those excluding pyrazinamide, may be used to mitigate the risk of liver injury. The rise in tuberculosis cases in 2022 underscores the ongoing global burden of this disease and the critical need for effective treatment strategies. Tailored therapeutic approaches, comprehensive liver function monitoring, and early identification of DILI are vital for minimizing hepatotoxicity while ensuring successful tuberculosis management. Although hepatoprotective drugs and alternative regimens show promise, further research is necessary to optimize their application across diverse patient populations. Highlights: 1. This article presents a thorough evaluation of antituberculosis drug-induced liver injury, particularly concerning its causes, diagnosis, and management, highlighting the importance of a meticulous differentiation from other liver disorders through a comprehensive assessment of clinical indicators. 2. The literature review included studies utilizing advanced diagnostic tools for precise causality determination as well as innovative approaches, such as the selective omission of pyrazinamide or the integration of non-standard treatment protocols, which offer promising avenues to mitigate hepatotoxicity risk. 3. This literature review suggests that hepatoprotective agents, such as N-acetylcysteine, may have advantages due to their notable efficacy in preserving liver function, offering a proactive strategy for patient safety.

Review

This literature review thoroughly addresses a critical concern in global health: drug-induced liver injury (DILI) associated with antituberculosis medications. Given the concerning rise in tuberculosis cases exceeding pre-pandemic levels in 2022, the need for effective treatment strategies is paramount. This review aptly focuses on evaluating DILI in the context of conventional antituberculosis therapy, specifically delving into its causes, diagnosis, and management. By highlighting that over 7% of patients may experience DILI, primarily due to isoniazid and rifampicin, the paper establishes the significant clinical relevance of understanding and mitigating this adverse effect, which can severely compromise treatment adherence and outcomes. The review effectively consolidates current knowledge regarding risk factors for antituberculosis DILI, including age, sex (with advanced age and female sex being significant contributors to severe injury), genetic predisposition, and pre-existing liver conditions. It meticulously outlines the diagnostic challenges, emphasizing the need for careful differentiation from other hepatic disorders through clinical presentation, liver function tests, and clinical assessments. Furthermore, the paper provides a comprehensive overview of management strategies, from prompt drug discontinuation and close monitoring to gradual reintroduction of less hepatotoxic options and the use of alternative regimens, particularly those excluding pyrazinamide. The inclusion of innovative approaches, such as the selective omission of pyrazinamide and the integration of hepatoprotective agents like N-acetylcysteine, underscores the review's strength in exploring practical avenues for risk mitigation. Ultimately, this literature review serves as a valuable resource for clinicians and researchers navigating the complexities of tuberculosis treatment. It underscores the critical need for tailored therapeutic approaches, comprehensive liver function monitoring, and early identification of DILI to ensure successful tuberculosis management while minimizing hepatotoxicity. While the review effectively synthesizes existing knowledge and proposes promising strategies, it also judiciously acknowledges the limitation that further research is necessary to optimize the application of hepatoprotective drugs and alternative regimens across diverse patient populations. This call for continued investigation ensures the review contributes not only to current practice but also to future advancements in patient safety and treatment efficacy in tuberculosis.

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