A 28-year-old male with newly diagnosed pulmonary TB is enrolled in RNTCP. His sputum smear converts to negative by 2 months. However, at 4 months of treatment, he develops jaundice with elevated transaminases (ALT 180 U/L, AST 200 U/L, bilirubin 3.2 mg/dL). What is the most appropriate next step?

Explanation

## Management of Drug-Induced Hepatotoxicity During TB Treatment **Key Point:** Drug-induced liver injury (DILI) during TB therapy is a known adverse effect of INH, RIF, and PZA. Management depends on severity and timing. At 4 months with significant elevation (ALT/AST >3× ULN, bilirubin >2.5 mg/dL), the hepatotoxic drugs must be withheld and reintroduced sequentially. ### Classification of TB Drug-Induced Hepatotoxicity | Severity | ALT/AST | Bilirubin | Action | |----------|---------|-----------|--------| | Mild | <3× ULN | <2.5 mg/dL | Monitor, continue if asymptomatic | | Moderate | 3–5× ULN | 2.5–5 mg/dL | Stop hepatotoxic drugs; reintroduce sequentially | | Severe | >5× ULN | >5 mg/dL | Stop all drugs; hospitalize; reintroduce cautiously | **High-Yield:** The patient in this case has **moderate hepatotoxicity** (ALT 180, AST 200, bilirubin 3.2). RNTCP protocol mandates: 1. **Immediately discontinue INH, RIF, and PZA** 2. **Continue ethambutol and streptomycin** (non-hepatotoxic agents) 3. **Monitor LFTs weekly** 4. **Reintroduce drugs sequentially** once LFTs improve (typically after 1–2 weeks): - Start with RIF (most potent anti-TB agent) - After 3–5 days, add INH - Finally, add PZA 5. **Restart from the beginning** of the regimen to complete full course ### Reintroduction Algorithm ```mermaid flowchart TD A[DILI during TB treatment]:::outcome --> B{Severity?}:::decision B -->|Mild: ALT<3×ULN| C[Monitor, continue if asymptomatic]:::action B -->|Moderate: ALT 3-5×ULN| D[Stop INH, RIF, PZA]:::action B -->|Severe: ALT>5×ULN| E[Stop all drugs, hospitalize]:::urgent D --> F[Continue ETH + SM]:::action F --> G[Monitor LFTs weekly]:::action G --> H{LFTs improving?}:::decision H -->|Yes, after 1-2 weeks| I[Reintroduce RIF first]:::action H -->|No| J[Extend monitoring period]:::action I --> K[After 3-5 days, add INH]:::action K --> L[After 3-5 days, add PZA]:::action L --> M[Complete full course from restart point]:::action ``` **Clinical Pearl:** Streptomycin and ethambutol are safe to continue during hepatotoxicity episodes. Reintroduction must be sequential to identify which drug caused the injury. **Warning:** Continuing all drugs despite significant hepatotoxicity risks acute liver failure. Conversely, stopping all drugs and restarting without a tapering/sequential approach risks re-precipitation of DILI. [cite:Park 26e Ch 9; RNTCP Adverse Drug Reaction Management Guidelines]