Drug-Induced Liver Injury During First-Line Anti-Tubercular Therapy (Isoniazid, Rifampicin, Pyrazinamide, and Ethambutol): A Case Report with De-challenge and Rechallenge.

BACKGROUND: The primary treatment for tuberculosis, which includes isoniazid, rifampicin, pyrazinamide, and ethambutol, is vital for managing the disease but often leads to drug-induced liver injury (DILI), especially in older adults. It is important to accurately identify and manage hepatotoxicity caused by this treatment to safely continue therapy. OBJECTIVE: This report discusses a case of liver injury induced by first-line anti-tubercular drugs in an elderly patient, emphasiz-ing the importance of de-challenge, alternative non-hepatotoxic treatments, and a carefully monitored stepwise rechallenge. METHODS: An 84-year-old woman with pulmonary tuberculosis and hypertension (treated with amlodipine) experienced abnormal liver function tests after starting first-line anti-tubercular therapy. A thorough clinical evaluation, laboratory tests, causality assessment, de-challenge, alternative treatment, and stepwise rechallenge were conducted with close biochemical monitoring. RESULTS: Initial tests showed significant hyperbilirubinemia (total bilirubin 5.2 mg/dL), elevated aspartate aminotransferase (AST 176-247 U/L), slightly increased Alanine Aminotransferase (ALT 40-55 U/L), and an R-ratio of about 2.6, indicating a predominantly cholestatic pattern with mixed features of liver injury. After discontinuing the hepatotoxic treatment and starting alternative medications (Moxifloxacin, Streptomycin, and Ethambutol), liver function tests improved significantly within 3-5 days. Once liver parameters normalized, Rifampicin was gradually reintroduced, and liver function tests remained stable four days after rechallenge, with no return of hepatotoxicity. CONCLUSION: This case illustrates that early detection of liver injury from anti-tubercular therapy, prompt de-challenge, use of alternative non-hepatotoxic drugs, and a carefully monitored stepwise rechallenge can enable the safe continuation of tuberculosis treatment in elderly patients. Close biochemical monitoring, along with consideration of therapeutic drug monitoring, may further improve patient safety.