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

Liver Transpl. 2010 Oct;16(10):1136-46. doi: 10.1002/lt.22125.

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.

MeSH terms

  • Adolescent
  • Adult
  • Antitubercular Agents / adverse effects*
  • Chemical and Drug Induced Liver Injury / etiology
  • Chemical and Drug Induced Liver Injury / mortality
  • Chemical and Drug Induced Liver Injury / surgery*
  • Disease Progression
  • Drug Therapy, Combination
  • Female
  • France
  • Graft Rejection / etiology
  • Humans
  • Isoniazid / adverse effects
  • Liver Failure, Acute / chemically induced
  • Liver Failure, Acute / mortality
  • Liver Failure, Acute / surgery*
  • Liver Transplantation* / adverse effects
  • Liver Transplantation* / mortality
  • Male
  • Middle Aged
  • Remission, Spontaneous
  • Rifampin / adverse effects
  • Risk Assessment
  • Risk Factors
  • Time Factors
  • Treatment Outcome
  • Tuberculosis / diagnosis
  • Tuberculosis / drug therapy*
  • Tuberculosis / mortality
  • Young Adult

Substances

  • Antitubercular Agents
  • Isoniazid
  • Rifampin