Skip to main content
Top
Published in: Indian Journal of Pediatrics 3/2019

01-03-2019 | Original Article

Revised Antituberculosis Drug Doses and Hepatotoxicity in HIV Negative Children

Authors: C. K. Indumathi, Aruna Sethuraman, Saurav Jain, Savita Krishnamurthy

Published in: Indian Journal of Pediatrics | Issue 3/2019

Login to get access

Abstract

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.
Literature
1.
go back to reference Tostmann A, Boeree MJ, Aarnoutse RE, De Lange W, Van Der Ven AJ, Dekhuijzen R. Antituberculosis drug-induced hepatotoxicity: concise up-to-date review. J Gastroenterol Hepatol. 2008;23:192–202.CrossRefPubMed Tostmann A, Boeree MJ, Aarnoutse RE, De Lange W, Van Der Ven AJ, Dekhuijzen R. Antituberculosis drug-induced hepatotoxicity: concise up-to-date review. J Gastroenterol Hepatol. 2008;23:192–202.CrossRefPubMed
2.
go back to reference Devarbhavi H. Antituberculous drug-induced liver injury: current perspective. Trop Gastroenterol. 2011;32:167–74.PubMed Devarbhavi H. Antituberculous drug-induced liver injury: current perspective. Trop Gastroenterol. 2011;32:167–74.PubMed
3.
go back to reference Donald PR. Antituberculosis drug-induced hepatotoxicity in children. Pediatr Rep. 2011;3:51–64.CrossRef Donald PR. Antituberculosis drug-induced hepatotoxicity in children. Pediatr Rep. 2011;3:51–64.CrossRef
4.
go back to reference Devrim İ, Olukman Ö, Can D, Dizdarer C. Risk factors for isoniazid hepatotoxicity in children with latent TB and TB: difference from adults. Chest. 2010;137:737–8.CrossRefPubMed Devrim İ, Olukman Ö, Can D, Dizdarer C. Risk factors for isoniazid hepatotoxicity in children with latent TB and TB: difference from adults. Chest. 2010;137:737–8.CrossRefPubMed
5.
go back to reference Kumar A, Sood V, Khanna R, et al. Clinical spectrum and outcome of pediatric drug induced liver injury. Indian J Pediatr. 2017;85:676–8.CrossRefPubMed Kumar A, Sood V, Khanna R, et al. Clinical spectrum and outcome of pediatric drug induced liver injury. Indian J Pediatr. 2017;85:676–8.CrossRefPubMed
7.
go back to reference Swaminathan S, Rekha B. Pediatric tuberculosis: global overview and challenges. Clin Infect Dis. 2010;50:S184–94.CrossRefPubMed Swaminathan S, Rekha B. Pediatric tuberculosis: global overview and challenges. Clin Infect Dis. 2010;50:S184–94.CrossRefPubMed
8.
go back to reference Mukherjee A, Velpandian T, Singla M, Kanhiya K, Kabra SK, Lodha R. Pharmacokinetics of isoniazid, rifampicin, pyrazinamide and ethambutol in Indian children. BMC Infect Dis. 2015;15:126.CrossRefPubMedPubMedCentral Mukherjee A, Velpandian T, Singla M, Kanhiya K, Kabra SK, Lodha R. Pharmacokinetics of isoniazid, rifampicin, pyrazinamide and ethambutol in Indian children. BMC Infect Dis. 2015;15:126.CrossRefPubMedPubMedCentral
9.
go back to reference Ohkawa K, Hashiguchi M, Ohno K, et al. Risk factors for antituberculous chemotherapy-induced hepatotoxicity in Japanese pediatric patients. Clin Pharmacol Ther. 2002;72:220–6.CrossRefPubMed Ohkawa K, Hashiguchi M, Ohno K, et al. Risk factors for antituberculous chemotherapy-induced hepatotoxicity in Japanese pediatric patients. Clin Pharmacol Ther. 2002;72:220–6.CrossRefPubMed
10.
go back to reference Mansukhani S, Shah I. Hepatic dysfunction in children with tuberculosis on treatment with antituberculous therapy. Ann Hepatol. 2012;11:96–9.CrossRef Mansukhani S, Shah I. Hepatic dysfunction in children with tuberculosis on treatment with antituberculous therapy. Ann Hepatol. 2012;11:96–9.CrossRef
11.
go back to reference Aishatu G, Rasheedah I, Wahab J, Sheni M, Damilola O, Adeniyi O. Hepatotoxicity due to antituberculosis therapy among paediatric patients seen at the University of Ilorin Teaching Hospital, north Central Nigeria. Ethiop J Health Sci. 2017;27:115–20.CrossRefPubMedPubMedCentral Aishatu G, Rasheedah I, Wahab J, Sheni M, Damilola O, Adeniyi O. Hepatotoxicity due to antituberculosis therapy among paediatric patients seen at the University of Ilorin Teaching Hospital, north Central Nigeria. Ethiop J Health Sci. 2017;27:115–20.CrossRefPubMedPubMedCentral
12.
go back to reference Saukkonen JJ, Cohn DL, Jasmer RM, et al. An official ATS statement: hepatotoxicity of antituberculosis therapy. Am J Respir Crit Care Med. 2006;174:935–52.CrossRefPubMed Saukkonen JJ, Cohn DL, Jasmer RM, et al. An official ATS statement: hepatotoxicity of antituberculosis therapy. Am J Respir Crit Care Med. 2006;174:935–52.CrossRefPubMed
13.
go back to reference Nolan CM, Goldberg SV, Buskin SE. Hepatotoxicity associated with isoniazid preventive therapy: a 7-year survey from a public health tuberculosis clinic. JAMA. 1999;281:1014–8.CrossRefPubMed Nolan CM, Goldberg SV, Buskin SE. Hepatotoxicity associated with isoniazid preventive therapy: a 7-year survey from a public health tuberculosis clinic. JAMA. 1999;281:1014–8.CrossRefPubMed
14.
go back to reference Indumathi C, Kumar G, Sethuraman A, Iyengar A. Evaluation of efficacy and adherence to INH preventive therapy in children at risk to develop active tuberculosis. Pediatr Infect Dis. 2014;6:21–4.CrossRef Indumathi C, Kumar G, Sethuraman A, Iyengar A. Evaluation of efficacy and adherence to INH preventive therapy in children at risk to develop active tuberculosis. Pediatr Infect Dis. 2014;6:21–4.CrossRef
15.
go back to reference 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.CrossRefPubMedPubMedCentral 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.CrossRefPubMedPubMedCentral
16.
go back to reference McIlleron H, Willemse M, Werely CJ, et al. Isoniazid plasma concentrations in a cohort of south African children with tuberculosis: implications for international pediatric dosing guidelines. Clin Infect Dis. 2009;48:1547–53.CrossRefPubMed McIlleron H, Willemse M, Werely CJ, et al. Isoniazid plasma concentrations in a cohort of south African children with tuberculosis: implications for international pediatric dosing guidelines. Clin Infect Dis. 2009;48:1547–53.CrossRefPubMed
17.
go back to reference 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.PubMed 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.PubMed
Metadata
Title
Revised Antituberculosis Drug Doses and Hepatotoxicity in HIV Negative Children
Authors
C. K. Indumathi
Aruna Sethuraman
Saurav Jain
Savita Krishnamurthy
Publication date
01-03-2019
Publisher
Springer India
Published in
Indian Journal of Pediatrics / Issue 3/2019
Print ISSN: 0019-5456
Electronic ISSN: 0973-7693
DOI
https://doi.org/10.1007/s12098-018-2812-z

Other articles of this Issue 3/2019

Indian Journal of Pediatrics 3/2019 Go to the issue