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

Table 1 Summary of pediatric studies on antitubercular therapy-induced hepatotoxicity in children

Ref.	Terminologies	Definition	Prevalence	Monitoring	Management
Mehra et al[9]	TB-DILI	Any 1: ALT/AST > 3 × ULN with symptoms; ALT/AST > 5 × ULN without symptoms; bilirubin > 1.5 mg/dL	12.3%	LFT baseline, 2/4/6 weeks, then every 2 months	Stop ATT, monitor LFTs every 3–5 days; Reintroduce full doses sequentially (Rifampicin, then Isoniazid, then Pyrazinamide)
Gafar et al[10]	ATLI	Any 1: ALT/AST > 3 × ULN with symptoms (> 5 × ULN without symptoms); bilirubin > 2 mg/dL with jaundice	26.8%	LFT at baseline, and 2 weeks. Then 4, 6, 8 weeks if 2 weeks LFT was abnormal	LFT weekly, Reintroduction of all 3 drug simultaneously
Yunivita et al[11]	ADIH	ALT/AST > 3 × ULN or > 1.5 × ULN if baseline is abnormal	27.9%	Not mentioned	Not mentioned
Indumathi et al[12]	ATDH	ALT > 3 or 5 × ULN with or without symptoms	2.7%	Clinical follow-up every 2 weeks (in IP); every 1 month (in CP)	Stop ATT; Rifampicin, INH and pyrazinamide were restarted in sequential manner
Aishatu et al[13]	Hepatotoxicity	ALT or AST > 3 × ULN	0%	LFT at baseline, at 2 and 5 months	ATT stopped; gradual reintroduction: Rifampicin first, then isoniazid
Nataprawira et al[14]	ADIH	Jaundice and/or total bilirubin > 1.5 mg/dL; and/or ALT > 3-5 × ULN above normal levels	3.5%	Not mentioned	Not mentioned
Hotchandani et al[15]	ATDIH	Jaundice and/or total bilirubin > 1.5 mg/dL; ALT 3-5 × ULN above normal level	13.92%	LFT baseline, 2/4/6 weeks, then every 2 months	ATT stopped; LFT twice per week; low-dose Rifampicin (7 days), then low-dose Isoniazid (7 days); increase doses of both over 10-14 days. PZA after 2 weeks
Mansukhani et al[16]	Hepatic Dysfunction	SGPT > 3 × ULN	15.2%	SGPT at baseline and after 15 days, then every 2 months	Not mentioned

TB-DILI: Tuberculosis drug-induced liver injury; ATLI: Antituberculosis liver injury, ADIH: Antituberculosis drug-induced hepatitis; ATDH: Antituberculosis drug hepatotoxicity; ATDIH: Antituberculosis drug-induced hepatotoxicity; ×: Times of; ATT: Antitubercular therapy; CLD: Chronic liver disease; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; LFT: Liver function test; ULN: Upper limit of normal; IP: Intensive Phase; CP: Continuation Phase; INH: Isoniazid.