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Hepatotoxic effects of therapies for tuberculosis

Nature Reviews Gastroenterology & Hepatology volume 7, pages 543–556 (2010)Cite this article

Subjects

Abstract

Hepatotoxic effects attributable to antituberculosis therapy are considered unique among drug-related liver problems because almost all first-line antituberculosis medications have such adverse effects, which vary in severity according to the drug and the regimen. In addition, all regimens for the treatment of active tuberculosis include a combination of medications that must typically be administered for at least 6 months to ensure complete cure of the disease and to minimize the development of drug-resistant bacterial strains. Hepatotoxic effects are a serious problem in patients who are undergoing treatment for tuberculosis, not only because of the morbidity and mortality they directly cause, but also because the liver symptoms can necessitate interruption of therapy or affect a patient's adherence to it, which can limit the efficacy of the antitubercular regimen.

Key Points

  • Tuberculosis is one of the most important infectious diseases worldwide; one-third of the global population is infected with mycobacteria

  • Almost all first-line antituberculosis medications have hepatotoxic effects but the degree of hepatotoxicity can vary considerably from one medication to another

  • Well-established environmental and patient-related risk factors enable practitioners to anticipate the hepatotoxic effect of antituberculosis medications

  • The hepatotoxic effects of antituberculosis medications can be prevented by first assessing the patient risk, selecting an appropriate initial regimen and finally monitoring liver function during therapy

  • In most patients, even if hepatotoxic effects develop, severe liver injury can be avoided and antituberculosis therapy can be completed by following a comprehensive management algorithm

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Figure 1: Simplified schematic of isoniazid metabolism.
Figure 2: Suggested algorithm for the management of hepatotoxic effects associated with antituberculosis medication based on clinical experience and data from guidelines produced by the American Thoracic Society, the European Respiratory Society, the WHO, the International Union against Tuberculosis and Lung Disease and the British Thoracic Society.

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Authors and Affiliations

  1. Internal Medicine Department, Ain Shams University, Cairo, 11566, Abbassia, Egypt

    Bahaa E. Senousy

  2. Forensic Medicine and Clinical Toxicology Department, Ain Shams University, Cairo, 11566, Abbassia, Egypt

    Sanaa I. Belal

  3. Division of Gastroenterology, University of Florida, Hepatology and Nutrition, 1600 SW Archer Road, Room HD 602, P. O. Box 100214, Gainesville, 32610, FL, USA

    Peter V. Draganov

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  1. Bahaa E. Senousy
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  3. Peter V. Draganov
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B. E. Senousy, S. I. Belal and P. V. Draganov researched the data for the article, provided a substantial contribution to discussions of the content and contributed equally to writing the article. P. V. Draganov reviewed and edited the manuscript before submission.

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Correspondence to Peter V. Draganov.

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Senousy, B., Belal, S. & Draganov, P. Hepatotoxic effects of therapies for tuberculosis. Nat Rev Gastroenterol Hepatol 7, 543–556 (2010). https://doi.org/10.1038/nrgastro.2010.134

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