Revised Antituberculosis Drug Doses and Hepatotoxicity in HIV Negative Children
- 61 Downloads
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).
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.
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.
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.
KeywordsAntituberculosis Drug induced hepatotoxicity Revised doses
ICK was responsible for study concept, study design and writing the paper. All authors were involved in clinical care, data collection and revision of the manuscript.
Compliance with Ethical Standards
Conflict of Interest
Source of Funding
- 2.Devarbhavi H. Antituberculous drug-induced liver injury: current perspective. Trop Gastroenterol. 2011;32:167–74.Google Scholar
- 6.World Health Organization. Rapid Advice: Treatment of Tuberculosis in Children. 2010; Available at: www.who.int/tb/publications. Accessed 19 July 2018.
- 10.Mansukhani S, Shah I. Hepatic dysfunction in children with tuberculosis on treatment with antituberculous therapy. Ann Hepatol. 2012;11:96–9.Google Scholar
- 15.Thee S, Seddon JA, Donald PR, et al. Pharmacokinetics of isoniazid, rifampin, and pyrazinamide in children younger than two years of age with tuberculosis: evidence for implementation of revised World Health Organization recommendations. Antimicrob Agents Chemother. 2011;55:5560–7.CrossRefGoogle Scholar
- 17.Mandal PK, Mandal A, Bhattacharyya SK. Comparing the daily versus the intermittent regimens of the anti-tubercular chemotherapy in the initial intensive phase in non-HIV, sputum positive, pulmonary tuberculosis patients. J Clin Diagn Res. 2013;7:292–5.Google Scholar