title: Hepatotoxicity during treatment for multidrug-resistant tuberculosis: occurrence, management and outcome.
abstract: METHODS
  Multidrug-resistant tuberculosis (MDR-TB) treatment program in Tomsk, Russia.
  
  
  OBJECTIVE
  To describe the incidence and management of hepatotoxicity during treatment of MDR-TB, and to assess risk factors associated with its development and impact on treatment outcomes.
  
  
  METHODS
  A retrospective case series performed among 608 patients.
  
  
  RESULTS
  Hepatotoxicity, using American Thoracic Society (2006) definitions, was observed in 91/568 patients (16.5%). The median time to the first hepatotoxic event was 196 days post treatment commencement. Baseline factors associated  with hepatotoxicity included elevated alanine aminotransferase/aspartate aminotransferase/bilirubin (OR 53.9, 95%CI 6.30-438.7), and renal insufficiency (OR 19.6, 95%CI 2.71-141.6). High treatment adherence (OR 3.25, 95%CI 2.07-5.09) and starting treatment in prison (OR 1.77,  95%CI 1.04-3.01) were associated with treatment success. Smoking (OR 0.44, 95%CI 0.21-0.92) and bilateral cavitary disease (OR 0.51, 95%CI 0.34-0.77) were associated with worse outcomes. For alcohol users, developing hepatotoxicity was associated with better outcomes (OR  4.40, 95%CI 1.79-10.81) than not (OR 0.42, 95%CI 0.25-0.68). One or more medications were permanently stopped in 10/91 patients, but in no case was treatment entirely discontinued.
  
  
  CONCLUSIONS
  MDR-TB treatment in the face of hepatotoxicity during therapy did not result in a  statistically significant increase in poor outcomes.
authors.affiliation: Program in Infectious Disease and Social Change, Department of Global Health and Social Medicine, Harvard Medical School, Boston, Massachusetts 02139, USA. Salmaan_Keshavjee@hms.harvard.edu
authors.forename: S
authors.initials: S
authors.lastname: Keshavjee
authors.forename: I Y
authors.initials: IY
authors.lastname: Gelmanova
authors.forename: S S
authors.initials: SS
authors.lastname: Shin
authors.forename: S P
authors.initials: SP
authors.lastname: Mishustin
authors.forename: Y G
authors.initials: YG
authors.lastname: Andreev
authors.forename: S
authors.initials: S
authors.lastname: Atwood
authors.forename: J J
authors.initials: JJ
authors.lastname: Furin
authors.forename: A
authors.initials: A
authors.lastname: Miller
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000428:Alcohol Drinking / Q000453:epidemiology; D000995:Antitubercular Agents / Q000009:adverse effects* / Q000627:therapeutic use; D056486:Chemical and Drug Induced Liver Injury / Q000453:epidemiology / Q000209:etiology* / Q000628:therapy; D005260:Female; D006801:Humans; D008297:Male; D055118:Medication Adherence; D008875:Middle Aged; D011329:Prisoners / Q000706:statistics & numerical data; D012189:Retrospective Studies; D012307:Risk Factors; D012426:Russia / Q000453:epidemiology; D012907:Smoking / Q000009:adverse effects; D013997:Time Factors; D016896:Treatment Outcome; D018088:Tuberculosis, Multidrug-Resistant / Q000188:drug therapy*; D055815:Young Adult
chemical_list: D000995:Antitubercular Agents