Revised Antituberculosis Drug Doses and Hepatotoxicity in HIV Negative Children.

OBJECTIVES: To compare the incidence of anti tuberculosis drug-induced hepatotoxicity (ATDH) with those on old vs. revised WHO doses in human immunodeficiency virus (HIV) negative children. The secondary objective was to determine the overall incidence of hepatitis in children on Anti tubercular treatment (ATT) and isoniazid prophylactic therapy (IPT).

METHODS: Children attending pediatric outpatient / admitted in wards, on ATT/ IPT between January 2007 and December 2017 (11 y) were included. Children were divided into Group 1 (treated based on old doses, from January 2007 to December 2011) and Group 2 (treated based on revised doses from January 2012 to December 2017). Children with multi drug resistant tuberculosis (MDRTB) and pre-existing liver disease were excluded.

RESULTS: A total of 515 children were enrolled. Twelve children developed ATDH with an overall incidence of 2.3%. Five out of 260 (1.9%) developed hepatitis with old doses vs. 7 of the 255 (2.7%) with revised doses; this difference was not statistically significant. When calculated only for active TB (excluding children on IPT), overall incidence of hepatitis was 2.7%. Comparison between group 1 (2.04%) and group 2 (3.5%) was again not statistically significant. Ten out of 12 children who developed hepatitis were restarted on ATT without recurrence. No child on IPT developed hepatitis. There was no mortality.

CONCLUSIONS: Revised WHO dosing does not increase incidence of hepatitis compared to old dosing in HIV negative children. Overall incidence was 2.3%. Hepatitis did not occur with IPT.