title: The influence of risk factors on the severity of anti-tuberculosis drug-induced hepatotoxicity.
abstract: BACKGROUND
  Hepatotoxicity is one of the most serious adverse effects of anti-tuberculosis drugs (ATD). Although many risk factors have been associated with ATD-induced hepatotoxicity, their influence on hepatitis severity has not been studied systematically.
  
  
  OBJECTIVE
  To evaluate whether the presence of hepatotoxicity risk factors (advanced age, chronic liver disease, abuse of alcohol or other drugs or malnutrition) influences the severity of ATD-induced hepatotoxicity.
  
  
  METHODS
  A prospective cohort study of 471 active tuberculosis patients treated with isoniazid, rifampicin and pyrazinamide and followed in a tuberculosis clinic between January 1998 and July 2002. Incidence of hepatotoxicity and its severity according to the presence or absence of ATD-induced hepatitis risk factors was evaluated.
  
  
  RESULTS
  The incidence of ATD-induced hepatotoxicity (serum transaminase > 3 x the upper limit of normal [ULN]) was 18.2% (42/231 patients) in the risk factor group and 5.8% (14/240 patients) in the non-risk factor group (OR 3.5; 95% CI 1.9-6.7; P < 0.001). Severe hepatotoxicity (transaminase > 10 x ULN) occurred in 6.9% (16/231) of the risk factor group and in 0.4% (1/240) (OR 17.7; 95% CI 2.3-135; P < 0.001) of the group without risk factors.
  
  
  CONCLUSIONS
  ATD-induced hepatitis is significantly more frequent and more severe in patients with hepatotoxicity risk factors.
authors.affiliation: Tuberculosis Unit, Department of Pneumology, Xeral-Cíes University Hospital, Vigo, Pontevedra, Spain. jfv01po@saludalia.com
authors.forename: A
authors.initials: A
authors.lastname: Fernández-Villar
authors.forename: B
authors.initials: B
authors.lastname: Sopeña
authors.forename: J
authors.initials: J
authors.lastname: Fernández-Villar
authors.forename: R
authors.initials: R
authors.lastname: Vázquez-Gallardo
authors.forename: F
authors.initials: F
authors.lastname: Ulloa
authors.forename: V
authors.initials: V
authors.lastname: Leiro
authors.forename: M
authors.initials: M
authors.lastname: Mosteiro
authors.forename: L
authors.initials: L
authors.lastname: Piñeiro
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000995:Antitubercular Agents / Q000009:adverse effects*; D056486:Chemical and Drug Induced Liver Injury / Q000453:epidemiology* / Q000209:etiology*; D015331:Cohort Studies; D005260:Female; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012307:Risk Factors; D012720:Severity of Illness Index
chemical_list: D000995:Antitubercular Agents