title: Antituberculosis drug-induced hepatotoxicity: a comparison between patients with and without human immunodeficiency virus seropositivity.
abstract: BACKGROUND
  The prevalence and risk factors for rifampin, isoniazid and pyrazinamide hepatotoxicity were evaluated in HIV-infected subjects and controls.
  
  
  METHODS
  Patients with tuberculosis (30 HIV positive and 132 HIV negative), aged between 18 and 80 years-old, admitted to hospital in Brazil, from 2005 to 2007, were selected for this investigation. Three definitions of hepatotoxicity were used: I) a 3-fold increase in the lower limit of normal for alanine-aminotransferase (ALT); II) a 3-fold increase in the upper limit of normal (ULN) for ALT, and III) a 3-fold increase in the ULN for ALT plus a 2-fold increase in the ULN of total bilirubin.
  
  
  RESULTS
  In groups with and without HIV infection the frequency of hepatotoxicity I was 77% and 46%, respectively (p < 0.01). Using hepatotoxicity II and III definitions no difference was observed in the occurrence of antituberculosis drug-induced hepatitis. Of the 17 patients with hepatotoxicity by definition III, 3 presented no side effects and treatment was well tolerated. In 8 (36.4%) out of 22, symptoms emerged and treatment was suspended. Alcohol abuse was related to hepatotoxicity only for definition I.
  
  
  CONCLUSIONS
  Depending on the definition of drug-induced hepatitis, HIV infection may or may not be associated with hepatotoxicity. The impact that minor alterations in the definition had on the results was impressive. No death was related to drug-induced hepatotoxicity. The emergence of new symptoms after initiating antituberculosis therapy could not be attributed to hepatotoxicity in over one third of the cases.
authors.affiliation: Infectology and Tropical Medicine, Faculty of Medicine, Federal University of Minas Gerais, Belo Horizonte, MG.
authors.forename: Natalia Saldanha Magalhães
authors.initials: NS
authors.lastname: Coca
authors.forename: Marcelo Silva
authors.initials: MS
authors.lastname: Oliveira
authors.forename: Izabela
authors.initials: I
authors.lastname: Voieta
authors.forename: Carlos Maurício de Figueiredo
authors.initials: CM
authors.lastname: Antunes
authors.forename: José Roberto
authors.initials: JR
authors.lastname: Lambertucci
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000410:Alanine Transaminase / Q000097:blood; D000995:Antitubercular Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001663:Bilirubin / Q000097:blood; D016022:Case-Control Studies; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology*; D005260:Female; D015658:HIV Infections / Q000150:complications; D006801:Humans; D007538:Isoniazid / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D011718:Pyrazinamide / Q000009:adverse effects; D012293:Rifampin / Q000009:adverse effects; D012307:Risk Factors; D014376:Tuberculosis / Q000188:drug therapy; D055815:Young Adult
chemical_list: D000995:Antitubercular Agents; D011718:Pyrazinamide; D000410:Alanine Transaminase; D001663:Bilirubin; D007538:Isoniazid; D012293:Rifampin