Understanding antituberculosis drug-induced hepatotoxicity: Risk factors and effective management strategies in the pediatric population

Table 2 Management guidelines by various societies

	American Thoracic Society (2006: updated 2016) 14	British Thoracic Society (1998) 15	WHO (2010) 30	APASL (2021) 12	NTEP (2022) 16
Stopping hepatotoxic drugs in ATDIH	Yes	Yes	Yes	Yes	Yes
When to reintroduce ATT	ALT return to < 2 × ULN	ALT return to <2 × ULN	LFT return to normal and clinical Symptoms resolve	AST/ALT < 2× ULN Bilirubin < 1.5 × ULN	ALT return to < 2 × ULN
What drug and which regimen (sequentially or simultaneously)	RIF ± EMB full dose, after 3–7 days, INH full dose followed by PZA	INH → RIF→PZA (Dose titration every 2–3 days)	RIF→ introduce; INH after 3–7 days); PZA to avoid	RIF →INH→PZA (start low dose of each drug and titrate dose upwards every 3 days); Continue EMB full dose PZA (Restart only if mild DILI without jaundice)	RIF ± EMB full dose, after 3–7 days, INH full dose, followed by full dose PZA full dose
LFT monitoring during reintroduction	Check ALT 3–7 days after INH rechallenge	Daily Monitoring of LFT	LFT Monitoring (No recommendation on frequency)	Monitor LFT and INR every 3–7 days, earlier if symptoms arise	Check ALT 3–7 days after INH rechallenge

WHO: World Health Organization; APASL: Asia Pacific Association for the Study of the Liver; NTEP: National Tuberculosis Elimination Program, India; ATT: Antitubercular therapy; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; LFT: liver function test; ULN: Upper limit of normal; RIF: Rifampicin; INH: Isoniazid; EMB: ethambutol; PZA: Pyrazinamide; INR: International normalized ratio; DILI: Drug induced liver injury; →: Followed by; ×: Times of.