title: 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 ± 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.
authors.affiliation: Centre Hépato-BiliaireAP-HP Hôpital Paul Brousse, Villejuif, France. philippe.ichai@pbr.aphp.fr
authors.forename: Philippe
authors.initials: P
authors.lastname: Ichai
authors.forename: Faouzi
authors.initials: F
authors.lastname: Saliba
authors.forename: Fadi
authors.initials: F
authors.lastname: Antoun
authors.forename: Daniel
authors.initials: D
authors.lastname: Azoulay
authors.forename: Mylène
authors.initials: M
authors.lastname: Sebagh
authors.forename: Teresa Maria
authors.initials: TM
authors.lastname: Antonini
authors.forename: Lélia
authors.initials: L
authors.lastname: Escaut
authors.forename: Valérie
authors.initials: V
authors.lastname: Delvart
authors.forename: Denis
authors.initials: D
authors.lastname: Castaing
authors.forename: Didier
authors.initials: D
authors.lastname: Samuel
mesh_terms: D000293:Adolescent; D000328:Adult; D000995:Antitubercular Agents / Q000009:adverse effects*; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology / Q000401:mortality / Q000601:surgery*; D018450:Disease Progression; D004359:Drug Therapy, Combination; D005260:Female; D005602:France; D006084:Graft Rejection / Q000209:etiology; D006801:Humans; D007538:Isoniazid / Q000009:adverse effects; D017114:Liver Failure, Acute / Q000139:chemically induced / Q000401:mortality / Q000601:surgery*; D016031:Liver Transplantation / Q000009:adverse effects / Q000401:mortality; D008297:Male; D008875:Middle Aged; D012075:Remission, Spontaneous; D012293:Rifampin / Q000009:adverse effects; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D014376:Tuberculosis / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D055815:Young Adult
chemical_list: D000995:Antitubercular Agents; D007538:Isoniazid; D012293:Rifampin