Which TB drug is most associated with hepatotoxicity among the first-line agents?

Which TB drug is most associated with hepatotoxicity among the first-line agents?

• A. Pyrazinamide
• B. Isoniazid
• C. Rifampin
• D. Ethambutol

Answer: (B)

Hepatotoxicity risk varies among the first-line TB drugs, with isoniazid having the strongest association. Isoniazid is processed in the liver by acetylation. In individuals who are slow acetylators, a toxic metabolite (acetylhydrazine) can accumulate, leading to hepatocellular injury and hepatitis. This risk is the reason liver function monitoring is emphasized during INH therapy, especially in the early months, and why patients are advised to report fatigue, jaundice, dark urine, or right upper-quadrant pain. While other first-line drugs can also affect the liver, isoniazid is classically the most implicated. Pyrazinamide can raise liver enzymes as well, rifampin can cause milder hepatotoxicity, and ethambutol is not associated with liver injury (it’s mainly linked to optic neuritis). So, the drug most commonly linked to hepatotoxicity among these options is isoniazid.

Hepatotoxicity risk varies among the first-line TB drugs, with isoniazid having the strongest association. Isoniazid is processed in the liver by acetylation. In individuals who are slow acetylators, a toxic metabolite (acetylhydrazine) can accumulate, leading to hepatocellular injury and hepatitis. This risk is the reason liver function monitoring is emphasized during INH therapy, especially in the early months, and why patients are advised to report fatigue, jaundice, dark urine, or right upper-quadrant pain.

While other first-line drugs can also affect the liver, isoniazid is classically the most implicated. Pyrazinamide can raise liver enzymes as well, rifampin can cause milder hepatotoxicity, and ethambutol is not associated with liver injury (it’s mainly linked to optic neuritis). So, the drug most commonly linked to hepatotoxicity among these options is isoniazid.