Related Experiment Videos
Hepatotoxic reactions in children with severe tuberculosis treated with isoniazid-rifampin
Insights
High doses of isoniazid and rifampin (INH-RIF) in children with tuberculosis can cause liver injury. Careful dosing is crucial to prevent hepatotoxicity, especially in pediatric patients.
Area of Science:
- Pediatric Hepatology
- Infectious Disease Management
- Pharmacovigilance in Children
Background:
- Tuberculosis treatment in children often involves combination therapy.
- Hepatotoxicity is a known adverse effect of antitubercular drugs.
- Understanding drug-induced liver injury (DILI) in pediatric populations is critical.
Purpose of the Study:
- To prospectively evaluate the incidence and severity of liver injury in children treated with isoniazid and rifampin.
- To identify risk factors and clinical manifestations of hepatotoxicity in pediatric tuberculosis patients.
- To inform safe dosing recommendations for antitubercular therapy in children.
Main Methods:
- Prospective evaluation of 44 children (4 months to 14 years) receiving isoniazid (15-20 mg/kg/day) and rifampin (15 mg/kg/day).
- Monitoring of liver function tests, specifically serum alanine aminotransferase (ALT) levels.
- Clinical assessment for signs of hepatitis, jaundice, liver enlargement, and prothrombin time prolongation.
Main Results:
- Elevated ALT (>100 units) observed in 82% (36/44) of children.
- 15 patients developed clinical hepatitis with jaundice; 7 also showed liver enlargement and prolonged prothrombin time.
- Hepatotoxicity onset occurred between 6-30 days (mean 14 days) of treatment; biochemical recovery was noted in most survivors without regimen changes.
Conclusions:
- The combination of isoniazid and rifampin at the studied doses is associated with a high incidence of hepatotoxicity in children.
- Hepatocellular damage may be linked to the release of tubercle bacilli products following drug-induced bacterial destruction.
- The study strongly warns against exceeding 10 mg INH/kg/day when co-administered with rifampin in pediatric tuberculosis treatment to mitigate liver injury risk.
Abstract:
The incidence and degree of liver injury was prospectively evaluated in 44 children, ages between 4 months and 14 years (mean age, 4.5 years) treated for tuberculosis with 15 to 20 mg isoniazid/kg/day and 15 mg rifampin/kg/day (INH-RIF). None of the patients had hepatic dysfunction before initiation of treatment. Elevation of the serum alanine aminotransferase (ALT) concentration (greater than 100 units) occurred in 36 patients (82%). One patient with an increase in the ALT value had coincidental infection with hepatitis B. The incidence of hepatotoxicity did not correlate with the patients' age or sex. Fifteen of the 36 patients developed clinical hepatitis with jaundice. In 7 patients liver enlargement and prolongation of the prothrombin time were also observed. In all but one patient liver dysfunction was recognized 6 to 30 days (mean, 14 days) after start of treatment. Biochemical signs of hepatic injury in the 35 surviving patients regressed completely without alteration of the INH-RIF regimen in 22 patients. These facts suggest the possibility that hepatocellular damage may be due to the effect of tubercle bacilli products liberated in the liver after their destruction by antituberculous drugs. However, the high rate of hepatotoxic reactions warns that the dose of 10 mg INH/kg/day should not be exceeded when that drug is combined with RIF.