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Isoniazid/Rifampicin DILI — RACP Adult Medicine MCQ

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ModerateGastroenterologyIsoniazid/Rifampicin DILIRACP Adult Medicine

A 55-year-old man commenced on isoniazid and rifampicin for latent TB presents 6 weeks later with jaundice and markedly elevated transaminases (ALT 1500 U/L). ALP is only mildly elevated. Hepatitis serology is negative. He was well before TB treatment. What is the most likely hepatotoxicity pattern?

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Correct answer: E — Hepatocellular drug-induced liver injury

Markedly elevated transaminases (ALT predominant) with minimal ALP elevation after isoniazid/rifampicin initiation is hepatocellular DILI. R-factor = (ALT/ULN) ÷ (ALP/ULN) >5 = hepatocellular. Both isoniazid and rifampicin are hepatotoxic. Management: cease both drugs, monitor LFTs. Rechallenge may be attempted sequentially (rifampicin first, then isoniazid) once LFTs normalise if TB treatment is essential.

Reference: eTG Antibiotic – 2025 – TB; AASLD 2024 DILI Guidelines