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Open AccessJournal ArticleDOI

Antituberculosis drug-induced hepatotoxicity in children

Peter R. Donald
- 16 Jun 2011 - 
- Vol. 3, Iss: 2, pp 16
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TLDR
The use of the higher dosages of INH, RMP and PZA recently recommended by WHO is unlikely to result in a greater risk of ADIH in children, which is considerably lower in children than in adults.
Abstract
Recent increases in the dosages of the essential antituberculosis agents isoniazid (INH), rifampicin (RMP), pyrazinamide (PZA) for use in children recommended by World Health Organization have raised concerns regarding the risk of hepatotoxicity. Published data relating to the incidence and pathogenesis of antituberculosis drug-induced hepatotoxicity (ADIH), particularly in children, is reviewed. Amongst 12,708 children receiving chemoprophylaxis, mainly with INH, but also other combinations of INH, RMP and PZA only 1 case (0.06%) of jaundice was recorded and abnormal liver functions documented in 110 (8%) of the 1225 children studied. Excluding tuberculous meningitis (TBM) 8984 were children treated for tuberculosis disease and jaundice documented in 75 (0.83%) and abnormal liver function tests in 380 (9.9%) of the 3855 children evaluated. Amongst 717 children treated for TBM, however, jaundice occurred in 72 (10.8%) and abnormal LFT were recorded in 174 (52.9%) of those studied. Case reports document the occurrence of ADIH in at least 63 children. Signs and symptoms of ADIH were frequently ignored in the recorded cases. ADIH can occur in children at any age or at any dosage of INH, RMP or PZA, but the incidence of.ADIH is is considerably lower in children than in adults. Children with disseminated forms of disease are at greater risk of ADIH. The use of the higher dosages of INH, RMP and PZA recently recommended by WHO is unlikely to result in a greater risk of ADIH in children.

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Prevention, Diagnosis, and Treatment of Tuberculosis in Children and Mothers: Evidence for Action for Maternal, Neonatal, and Child Health Services

TL;DR: Tuberculosis screening using a simple clinical algorithm that relies on the absence of current cough, fever, weight loss, and night sweats should be used to identify eligible pregnant women living with HIV for isoniazid preventive therapy or for further investigation for tuberculosis disease as part of services for prevention of vertical HIV transmission.
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Short intensified treatment in children with drug-susceptible tuberculous meningitis.

TL;DR: A 12-month course of antituberculous treatment for children with tuberculous meningitis is recommended by the World Health Organization and similar completion and relapse rates comparing 6-month treatment with 12- month treatment are reported.
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Key factors of susceptibility to anti-tuberculosis drug-induced hepatotoxicity

TL;DR: The mechanisms of ATDH and the key factors of susceptibility associated with drug metabolism, hepatic transport, immune response and oxidative stress are focused on.
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Clinical peculiarities of tuberculosis

TL;DR: An overview on the most important peculiarities of TB in children is provided to provide an overview of the ongoing spread of tuberculosis in poor resource countries and the recently increasing incidence in high resource countries.
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Hepatocyte Growth Factor Protects Against Isoniazid/Rifampicin-Induced Oxidative Liver Damage

TL;DR: HGF demonstrated to be a good protective factor against antituber tuberculosis drug-induced hepatotoxicity and could be considered a good adjuvant factor for the use of high doses of or the reintroduction of these antituberculosis drugs.
References
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Book ChapterDOI

Council for International Organizations of Medical Sciences

Z. Bankowski
TL;DR: The main aim of the conference, as expressed in its title, is to improve drug safety through the joint efforts of all those who are partners in this very complicated but crucial task of ensuring progress in medicine.
Journal ArticleDOI

An official ATS statement: hepatotoxicity of antituberculosis therapy.

TL;DR: Systematic steps for prevention and management of TB DILI are recommended, including patient and regimen selection to optimize benefits over risks, effective staff and patient education, ready access to care for patients, good communication among providers, and judicious use of clinical and biochemical monitoring.
Journal ArticleDOI

Isoniazid liver injury: clinical spectrum, pathology, and probable pathogenesis

TL;DR: The clinical spectrum of isoniazid-induced liver injury seems to be clinically, biochemically, and histologically indistinguishable from viral hepatitis, except that the injury occurs primarily in persons older than 35 years, and a possible relation between susceptibility of patients to isoniaZid liver injury and rapid metabolism (acetylation) of the drug has been found.
Journal ArticleDOI

Hepatotoxicity associated with isoniazid preventive therapy: a 7-year survey from a public health tuberculosis clinic.

TL;DR: The rate of isoniazid hepatotoxicity during clinically monitored preventive therapy was lower than has been reported previously and Clinicians should have greater confidence in the safety of isonianzid preventive therapy.
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