title: Outcome and determinants of mortality in 269 patients with combination anti-tuberculosis drug-induced liver injury.
abstract: OBJECTIVE
  Worldwide anti-tuberculosis (TB) drug-induced liver disease (DILI) is an important cause of hepatotoxicity, and drug-induced acute liver failure (ALF). Reported series on anti-TB DILI are limited by a mix of cases with mild transaminase elevation or adaptation. Our aim was to analyze the clinical features, laboratory characteristics, outcome, and determine predictors of 90-day mortality.
  
  
  METHODS
  Single center analysis of consecutive cases of anti-TB DILI following combination anti-TB drugs exposure from 1997-2011.
  
  
  RESULTS
  Of the 269 patients, 191 (71%) experienced jaundice and 69 (25.7%) accounted for ALF. The mean age and treatment duration was 41.3 years and 1.9 months, respectively; males constituted 55.7%. DILI occurred throughout the course of treatment; three-quarters occurred within the first 2 months. HIV infection was present in 21 (7.8%). The 90-day mortality was 22.7%. DILI accompanied by jaundice (n = 191), encephalopathy (n = 69) or ascites (n = 69) resulted in mortality in 30%, 69.6% and 50.7%, respectively (P < 0.001). Age, gender, transaminase levels, HIV or hepatitis B surface antigen (HBsAg) status did not influence survival. Treatment duration, encephalopathy, ascites, bilirubin, serum albumin, international normalized ratio (INR), serum creatinine and leukocyte count were associated with mortality (P < 0.001). Multivariate logistic regression model for mortality, incorporating encephalopathy, albumin, bilirubin, INR, and creatinine yielded a C-statistic of 97%.
  
  
  CONCLUSIONS
  Anti-TB DILI occurs throughout treatment duration progressing to ALF in a quarter of patients. The overall mortality is 22.7%, which is higher when accompanied by jaundice, ascites or encephalopathy. An anti-TB DILI model, incorporating bilirubin, INR, encephalopathy, serum creatinine and albumin predicted mortality with C-statistic of 97%.
authors.affiliation: Department of Gastroenterology, St. John's Medical College Hospital, Bangalore, India. dennis.eurich@charite.de
authors.forename: Harshad
authors.initials: H
authors.lastname: Devarbhavi
authors.forename: Rajvir
authors.initials: R
authors.lastname: Singh
authors.forename: Mallikarjun
authors.initials: M
authors.lastname: Patil
authors.forename: Keyur
authors.initials: K
authors.lastname: Sheth
authors.forename: Channagiri Krishnamurthy
authors.initials: CK
authors.lastname: Adarsh
authors.forename: Girisha
authors.initials: G
authors.lastname: Balaraju
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000995:Antitubercular Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D001201:Ascites / Q000139:chemically induced; D001663:Bilirubin / Q000097:blood; D056486:Chemical and Drug Induced Liver Injury / Q000097:blood / Q000150:complications / Q000401:mortality*; D002648:Child; D002675:Child, Preschool; D003404:Creatinine / Q000097:blood; D004359:Drug Therapy, Combination / Q000009:adverse effects; D058625:End Stage Liver Disease / Q000139:chemically induced*; D004804:Eosinophils; D005260:Female; D015658:HIV Infections / Q000150:complications; D006801:Humans; D019934:International Normalized Ratio; D007565:Jaundice / Q000097:blood / Q000139:chemically induced; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D020258:Neurotoxicity Syndromes / Q000209:etiology; D011237:Predictive Value of Tests; D012709:Serum Albumin; D012720:Severity of Illness Index; D013997:Time Factors; D014376:Tuberculosis / Q000188:drug therapy; D055815:Young Adult
chemical_list: D000995:Antitubercular Agents; D012709:Serum Albumin; D003404:Creatinine; D001663:Bilirubin