A patient completes 6 months of RHEZ therapy for drug-sensitive TB. Monitoring for adverse effects at month 2 reveals asymptomatic elevated ALT (3× ULN). The correct management is:

• A Stop all four drugs immediately; restart one by one after liver function normalizes to identify the offending agent
• B Switch to a non-hepatotoxic regimen of streptomycin + ethambutol + fluoroquinolone immediately
• C Continue therapy if ALT is <5× ULN and patient is asymptomatic; monitor LFTs weekly; stop only if ALT rises >5× ULN or jaundice/symptoms develop ✓
• D Reduce all drug doses proportionally and continue the original regimen to maintain therapeutic levels

Explanation

Asymptomatic transaminase elevation up to 3× ULN without symptoms is acceptable and should not prompt treatment interruption. The RNTCP/WHO threshold for drug-induced liver injury (DILI) requiring treatment stoppage is ALT >5× ULN (in asymptomatic patients) or >3× ULN if accompanied by symptoms (jaundice, vomiting). If drugs are stopped, the sequence for re-introduction after normalization is: rifampicin first, then isoniazid, then pyrazinamide (most hepatotoxic). Pyrazinamide causes the most severe hepatotoxicity and may need to be omitted in severe DILI, extending treatment to 9 months.

Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.

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Written and medically reviewed by the StethoPrep medical team.