title: Antituberculosis drug-induced hepatotoxicity: concise up-to-date review.
abstract: The cornerstone of tuberculosis management is a 6-month course of isoniazid, rifampicin, pyrazinamide and ethambutol. Compliance is crucial for curing tuberculosis. Adverse effects often negatively affect the compliance, because they frequently require a change of treatment, which may have negative consequences for treatment outcome. In this paper we review the incidence, pathology and clinical features of antituberculosis drug-induced hepatotoxicity, discuss the metabolism and mechanisms of toxicity of isoniazid, rifampicin and pyrazinamide, and describe risk factors and management of antituberculosis drug-induced hepatotoxicity. The reported incidence of antituberculosis drug-induced hepatotoxicity, the most serious and potentially fatal adverse reaction, varies between 2% and 28%. Risk factors are advanced age, female sex, slow acetylator status, malnutrition, HIV and pre-existent liver disease. Still, it is difficult to predict what patient will develop hepatotoxicity during tuberculosis treatment. The exact mechanism of antituberculosis drug-induced hepatotoxicity is unknown, but toxic metabolites are suggested to play a crucial role in the development, at least in the case of isoniazid. Priorities for future studies include basic studies to elucidate the mechanism of antituberculosis drug-induced hepatotoxicity, genetic risk factor studies and the development of shorter and safer tuberculosis drug regimens.
authors.affiliation: Department of Pulmonary Diseases, and University Lung Center Dekkerswald, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands. a.tostmann@ulc.umcn.nl
authors.forename: Alma
authors.initials: A
authors.lastname: Tostmann
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Boeree
authors.forename: Rob E
authors.initials: RE
authors.lastname: Aarnoutse
authors.forename: Wiel C M
authors.initials: WC
authors.lastname: de Lange
authors.forename: Andre J A M
authors.initials: AJ
authors.lastname: van der Ven
authors.forename: Richard
authors.initials: R
authors.lastname: Dekhuijzen
mesh_terms: D000995:Antitubercular Agents / Q000009:adverse effects*; D056486:Chemical and Drug Induced Liver Injury; D004359:Drug Therapy, Combination; D006801:Humans; D015994:Incidence; D007538:Isoniazid / Q000009:adverse effects; D008107:Liver Diseases / Q000473:pathology / Q000503:physiopathology / Q000628:therapy; D011718:Pyrazinamide / Q000009:adverse effects; D012293:Rifampin / Q000009:adverse effects; D012307:Risk Factors; D014376:Tuberculosis / Q000188:drug therapy
chemical_list: D000995:Antitubercular Agents; D011718:Pyrazinamide; D007538:Isoniazid; D012293:Rifampin