title: A comparison between two strategies for monitoring hepatic function during antituberculous therapy.
abstract: BACKGROUND
  The optimum strategy for monitoring liver function during antituberculous therapy is unclear.
  
  
  OBJECTIVE
  To assess the value of the American Thoracic Society risk-factor approach for predicting drug-induced liver injury and to compare with a uniform policy of liver function testing in all patients at 2 weeks.
  
  
  METHODS
  We conducted an observational study of adult patients undergoing therapy for active tuberculosis at a tertiary center. All patients had alanine transferase measurement at baseline and 2 weeks following commencement of therapy. Sensitivity, specificity, and positive and negative predictive values were used to assess strategies.
  
  
  RESULTS
  There were 288 patients included, and 21 (7.3%) developed drug-induced liver injury (57.1% "early" at 2 wk and 42.9% "late," after 2 wk). There were increased rates of individuals with HIV infection in the early drug-induced liver injury group compared with no drug-induced liver injury and late drug-induced liver injury groups (33% vs. 7.1% vs. 0%; P = 0.004). The American Thoracic Society algorithm had a sensitivity and specificity of 66.7 and 65.6%, respectively, for prediction of early and 22.2% and 63.7% for late drug-induced liver injury. The uniform monitoring policy had poor sensitivity but better specificity (22.2 and 82.1%) for prediction of late drug-induced liver injury.
  
  
  CONCLUSIONS
  In our urban, ethnically diverse population, a risk-factor approach is neither sensitive nor specific for prediction of drug-induced liver injury. A uniform policy of liver function testing at 2 weeks is useful for prompt identification of a subgroup who develop early drug-induced liver injury and may offer better specificity in ruling out late drug-induced liver injury.
authors.affiliation: Department of Respiratory Medicine, St. Mary's Hospital, Imperial College Healthcare NHS Trust, London, UK.
authors.forename: Aran
authors.initials: A
authors.lastname: Singanayagam
authors.forename: Saranya
authors.initials: S
authors.lastname: Sridhar
authors.forename: Jaideep
authors.initials: J
authors.lastname: Dhariwal
authors.forename: Dalia
authors.initials: D
authors.lastname: Abdel-Aziz
authors.forename: Kerry
authors.initials: K
authors.lastname: Munro
authors.forename: David W
authors.initials: DW
authors.lastname: Connell
authors.forename: Peter M
authors.initials: PM
authors.lastname: George
authors.forename: Philip L
authors.initials: PL
authors.lastname: Molyneaux
authors.forename: Graham S
authors.initials: GS
authors.lastname: Cooke
authors.forename: Andrew K
authors.initials: AK
authors.lastname: Burroughs
authors.forename: Ajit
authors.initials: A
authors.lastname: Lalvani
authors.forename: Melissa
authors.initials: M
authors.lastname: Wickremasinghe
authors.forename: Onn Min
authors.initials: OM
authors.lastname: Kon
mesh_terms: D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D000995:Antitubercular Agents / Q000009:adverse effects / Q000627:therapeutic use*; D056486:Chemical and Drug Induced Liver Injury / Q000378:metabolism / Q000517:prevention & control*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008111:Liver Function Tests / Q000592:standards*; D008297:Male; D008875:Middle Aged; D008991:Monitoring, Physiologic / Q000592:standards*; D017410:Practice Guidelines as Topic; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012372:ROC Curve; D012307:Risk Factors; D014376:Tuberculosis / Q000188:drug therapy* / Q000378:metabolism
chemical_list: D000995:Antitubercular Agents; D000410:Alanine Transaminase