Hepatotoxic reactions in children with severe tuberculosis treated with isoniazid-rifampin

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 (>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.