title: Early monitoring for detection of antituberculous drug-induced hepatotoxicity.
abstract: OBJECTIVE
  We investigated the time of onset of antituberculous drug-induced hepatotoxicity (ADIH) and related characteristics.
  
  
  METHODS
  Adult patients (n = 1,031) treated with first-line antituberculous drugs between February 2009 and January 2013 were enrolled.
  
  
  RESULTS
  Of the 1,031 patients, 108 patients (10.5%) developed ADIH a mean of 39.6 ± 43.7 days after treatment initiation. Twenty-eight patients (25.9%) developed ADIH within 7 days, 73 (67.6%) within 30 days, and the rest after 30 days. The ≤ 30-day group was characterized by higher peak alanine aminotransferase (ALT) level and a high proportion of patients with maintenance of first-line antituberculous drugs compared to the > 30-day group. In subgroup analysis, the ≤ 7-day group was characterized by higher baseline aspartate aminotransferase and ALT, high proportion of patients with maintenance of first-line antituberculous drugs, and high proportion of patients with extrapulmonary tuberculosis compared to patients with ADIH that developed beyond 7 days. In multivariate analysis, serum ALT > 40 IU/L (odds ratio [OR], 2.995; 95% confidence interval [CI], 1.580 to 5.680; p = 0.001) and presence of anti-hepatitis C virus (OR, 4.204; 95% CI, 1.822 to 9.700, p = 0.001) were independent risk factors for development of ADIH.
  
  
  CONCLUSIONS
  Approximately 70% of the cases of ADIH occurred in the first month of antituberculous treatment, and were associated with continuation of the first-line drug regimen.
authors.affiliation: Department of Internal Medicine, Gyeongsang National University Hospital, Jinju, Korea.
authors.forename: Chang Min
authors.initials: CM
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, Gyeongsang National University Hospital, Jinju, Korea.
authors.forename: Sang Soo
authors.initials: SS
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, Gyeongsang National University Hospital, Jinju, Korea.
authors.forename: Jeong Mi
authors.initials: JM
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, Gyeongsang National University Hospital, Jinju, Korea.
authors.forename: Hyun Chin
authors.initials: HC
authors.lastname: Cho
authors.affiliation: Department of Internal Medicine, Gyeongsang National University Hospital, Jinju, Korea.
authors.forename: Wan Soo
authors.initials: WS
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Gyeongsang National University Hospital, Jinju, Korea.
authors.forename: Hong Jun
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Gyeongsang National University Hospital, Jinju, Korea.
authors.forename: Chang Yoon
authors.initials: CY
authors.lastname: Ha
authors.affiliation: Department of Internal Medicine, Gyeongsang National University Hospital, Jinju, Korea.
authors.forename: Hyun Jin
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Gyeongsang National University Hospital, Jinju, Korea.
authors.forename: Tae Hyo
authors.initials: TH
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Gyeongsang National University Hospital, Jinju, Korea.
authors.forename: Woon Tae
authors.initials: WT
authors.lastname: Jung
authors.affiliation: Department of Internal Medicine, Gyeongsang National University Hospital, Jinju, Korea.
authors.forename: Ok Jae
authors.initials: OJ
authors.lastname: Lee
mesh_terms: D000328:Adult; D000368:Aged; D000410:Alanine Transaminase / Q000097:blood; D000995:Antitubercular Agents / Q000009:adverse effects*; D001219:Aspartate Aminotransferases / Q000097:blood; D015415:Biomarkers / Q000097:blood; D056486:Chemical and Drug Induced Liver Injury / Q000097:blood / Q000175:diagnosis* / Q000209:etiology; D016009:Chi-Square Distribution; D004796:Clinical Enzyme Tests; D060085:Coinfection; D016903:Drug Monitoring / Q000379:methods*; D004359:Drug Therapy, Combination; D042241:Early Diagnosis; D005260:Female; D006505:Hepatitis / Q000150:complications / Q000175:diagnosis; D006801:Humans; D008111:Liver Function Tests; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016017:Odds Ratio; D011237:Predictive Value of Tests; D012189:Retrospective Studies; D012307:Risk Factors; D013997:Time Factors
chemical_list: D000995:Antitubercular Agents; D015415:Biomarkers; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase
keywords: Drug monitoring; Drug-induced liver injury; Republic of Korea; Tuberculosis