Antituberculosis drug-induced hepatotoxicity: Concise up-to-date review

• Published in: Journal of gastroenterology and hepatology Vol. 23; no. 2; pp. 192 - 202
• Main Authors: Tostmann, Alma, Boeree, Martin J, Aarnoutse, Rob E, De Lange, Wiel C M, Van Der Ven, Andre J A M, Dekhuijzen, Richard
• Format: Journal Article
• Language: English
• Published: Melbourne, Australia Blackwell Publishing Asia 01.02.2008; Blackwell Science
• Subjects: adverse effect; Antibacterial agents; Antibiotics. Antiinfectious agents. Antiparasitic agents; antitubercular agents; Antitubercular Agents - adverse effects; antituberculous treatment; Biological and medical sciences; Chemical and Drug Induced Liver Injury; Drug Therapy, Combination; Drug toxicity and drugs side effects treatment; drug-induced hepatitis; Gastroenterology. Liver. Pancreas. Abdomen; Humans; hydrazine; Incidence; isoniazid; Isoniazid - adverse effects; Liver Diseases - pathology; Liver Diseases - physiopathology; Liver Diseases - therapy; Liver. Biliary tract. Portal circulation. Exocrine pancreas; Medical sciences; Other diseases. Semiology; Pharmacology. Drug treatments; pyrazinamide; Pyrazinamide - adverse effects; rifampicin; rifampin; Rifampin - adverse effects; Risk Factors; toxic hepatitis; Toxicity: digestive system; Tuberculosis - drug therapy; Toxicity; toxic hepatitis; Hepatic disease; hydrazine; Review; Rifamycin; Pyrazinamide; Hepatitis; Antibiotic; Rifampicin; Treatment; adverse effect; antituberculous treatment; drug-induced hepatitis; rifampin; Digestive diseases; Antituberculous agent; antitubercular agents; Protein synthesis inhibitor; Antibacterial agent; Hepatotoxicity; Isoniazid; Bibliographic review
• ISSN: 0815-9319; 1440-1746
• DOI: 10.1111/j.1440-1746.2007.05207.x

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.