Acute liver failure due to antitubercular therapy: Strategy for antitubercular treatment before and after liver transplantation

Abstract

The standard antitubercular treatment (ATT), which consists of isoniazid (INH), rifampicin (RIF), ethambutol, and pyrazinamide (PZA), is the best available treatment for tuberculosis (TB). However, the hepatotoxicity of INH and PZA can be severe, and even after drug withdrawal, patients may require liver transplantation (LT). In these cases, the strategy for the treatment of TB is poorly defined. Between 1986 and 2008, 14 patients presented at our department with severe hepatitis secondary to INH and PZA treatment. Four of these patients were immunosuppressed: 2 after renal transplantation and 2 because of human immunodeficiency virus infection. In seven of the 14 patients an alternative ATT was begun on admission, which was well tolerated. Hepatitis improved spontaneously in 5 patients, and alternative ATT was continued for 9.3 6 4.2 months; 1 patient deteriorated and underwent LT, and 1 patient died. ATT was stopped definitively in 2 patients. Six patients required urgent LT, and alternative ATT was started after transplantation and was successful. Five patients receiving RIF had an episode of acute rejection. In conclusion, hepatitis secondary to ATT can be successfully treated with alternative anti-TB regimens. The use of RIF in LT patients may lead to acute rejection. RIF should therefore be avoided in these patients.

Prise en charge des infections chez les adultes transplantés d’organe(s)

“…Des formes latentes sont possibles malgré les performances des systèmes de détec-tion les plus récents [1]. Quand il existe une suspicion de tuberculose non documentée chez le donneur (découverte post-mortem de lésions pulmonaires suspectes chez un donneur de foie asymptomatique), l'administration d'isoniazide chez le receveur est préconisée pour une durée de 9 mois [8]. …”

Genetic Variations Associated with Anti-Tuberculosis Drug-Induced Liver Injury

“…AT-DILI is often diagnosed by the occurrence of elevated levels of liver function biomarkers, including aspartate aminotransferase (AST), alanine transaminase (ALT), and total bilirubin levels [10]. Hepatotoxicity induced by anti-TB drugs can lead to irreversible liver failure that requires liver transplantation [11]. If not recognized, such hepatotoxicity can be fatal.…”

Anti-tuberculosis treatments and risk of hepatocellular carcinoma in tuberculosis patients with liver cirrhosis: a population-based case–control study

“…Studies have reported INHand RIF-induced hepatotoxicities ranging from abnormal liver function test results to acute liver failure [14][15][16]. The toxicity of INH might originate from its metabolites, acetylhydrazine and hydrazine, which are generated by CYP450 [7].…”