Hepatotoxicity in Elderly Tuberculosis Patient With Low NAT2 Activity Receiving Isoniazid: A Case Report

Abstract

Background: Isoniazid is a medication used in the treatment of tuberculosis. Hepatotoxicity is a common side effect associated with this drug. Currently, studies have investigated the N-acetyltransferase 2 (NAT2) gene, which plays a role in the metabolism of isoniazid in the liver, converting it into non-hepatotoxic substances that are eliminated from the body. NAT2 polymorphisms determine acetylation phenotype, which can be classified into rapid, intermediate, and slow acetylators.

Case Presentation: A 92-year-old Thai female patient weighing 39.6 kg, diagnosed with pulmonary tuberculosis and malnutrition. Genetic testing showed that she had the slow acetylation phenotype of NAT2. The patient was started on a standard anti-tuberculosis regimen, which included isoniazid, rifampicin, pyrazinamide, and ethambutol, with a daily dose of 300 mg of isoniazid. Liver function tests, including aspartate aminotransferase (AST), alanine aminotransferase (ALT), and total bilirubin, were monitored regularly. After 16 days of treatment, the levels of AST increased to more than 3 times the upper limit of normal, with no clinical signs. By day 18, these levels surged to more than 5 times the upper limit, leading to a change in the treatment regimen to ethambutol, amikacin, and levofloxacin. Subsequently, AST levels decreased to below twice the normal range, allowing the reintroduction of rifampicin, ethambutol, and levofloxacin. Within 8 days, AST levels returned to normal.

Conclusions: This case study presents risk factors that may contribute to isoniazid-induced hepatotoxicity, including advanced age, low NAT2 enzyme activity, and the consideration of an appropriate duration for monitoring liver enzyme levels to prevent severe liver toxicity.