Pyrazinamide-Induced Hepatitis Complicated by Obstructive Hydrocephalus Secondary to Tuberculous Meningitis: A Case Report

Tuberculous meningitis recognized as the most devastating manifestation of tuberculosis, contributes to approximately 20% of childhood TB mortality. This case report focuses on a pediatric patient with obstructive hydrocephalus secondary to tubercular meningitis, complicated by pyrazinamide-induced hepatitis. The elevated dosages of essential antituberculosis agents for pediatric use, recommended by the World Health Organization, raise concerns about heightened hepatotoxicity risk. Drug-induced liver injury (DILI) from anti-tuberculosis drugs is defined as hepatic injury, due to anti-tuberculosis drugs as suggested by the international DILI Expert Working Group and American Thoracic Society and recent evidence questions the safety profile of pyrazinamide compared to earlier perceptions. The main objective of our study was to identify the anti-tubercular drug that caused hepatitis. The patient, a 10-month-old with a history of obstructive hydrocephalus due to TB meningitis, was started with anti-tubercular therapy for which the baby presented with yellowish discoloration of both eyes after 15 days of starting anti-tubercular therapy. Two months prior, an 8-month-old baby was admitted with insidious onset fever lasting for 8 days. Clinical and diagnostic findings, including head-to-toe examination, Cerebrospinal fluid (CSF) analysis, neuro sonogram, Contrast-enhanced magnetic resonance imaging (CEMRI) of the brain, and abdominal ultrasound, were detailed. Laboratory investigations revealed abnormal liver function and increased inflammatory markers. The liver being the metabolic factory of the body is responsible for drug metabolism and thereby more vulnerable to drug-induced liver injury. Identification of pyrazinamide as the specific hepatotoxic agent was established through dechallenge and rechallenge assessments. The patient's management plan was modified to incorporate non-tubercular medications. Adjustments to the treatment regimen, including the discontinuation of pyrazinamide, were executed, resulting in an extension of isoniazid and rifampicin therapy for 9 months. This study highlighted that follow-up requires screening for any hepatotoxicity besides general wellbeing of the patient helping in early detection and intervention that will reduce the risk of hepatic injury but also treatment failure. The case highlights the need for a multidisciplinary approach, individualized treatment plans, and close monitoring in pediatric tuberculosis cases, particularly considering neurological and hepatic complications. Further research and awareness are crucial for refining treatment guidelines and improving overall care.