title: Antituberculosis therapy-induced acute liver failure: magnitude, profile, prognosis, and predictors of outcome.
abstract: Antituberculosis therapy (ATT)-associated acute liver failure (ATT-ALF) is the commonest drug-induced ALF in South Asia. Prospective studies on ATT-ALF are lacking. The current study prospectively evaluated the magnitude, clinical course, outcome, and prognostic factors in ATT-ALF. From January 1986 to January 2009, 1223 consecutive ALF patients were evaluated: ATT alone was the cause in 70 (5.7%) patients. Another 15 (1.2%) had ATT and simultaneous hepatitis virus infection. In 44 (62.8%) patients, ATT was prescribed empirically without definitive evidence of tuberculosis. ATT-ALF patients were younger (32.87 [+/-15.8] years), and 49 (70%) of them were women. Most had hyperacute presentation; the median icterus encephalopathy interval was 4.5 (0-30) days. The median duration of ATT before ALF was 30 (7-350) days. At presentation, advanced encephalopathy and cerebral edema were present in 51 (76%) and 29 (41.4%) patients, respectively. Gastrointestinal bleed, seizures, infection, and acute renal failure were documented in seven (10%), five (7.1%), 26 (37.1%), and seven (10%) patients, respectively. Compared with hepatitis E virus (HEV) and non-A non-E-induced ALF, ATT-ALF patients had nearly similar presentations except for older age and less elevation of liver enzymes. The mortality rate among patients with ATT-ALF was high (67.1%, n = 47), and only 23 (32.9%) patients recovered with medical treatment. In multivariate analysis, three factors independently predicted mortality: serum bilirubin (>or=10.8 mg/dL), prothrombin time (PT) prolongation (>or=26 seconds), and grade III/IV encephalopathy at presentation.
  
  
  CONCLUSIONS
  ATT-ALF constituted 5.7% of ALF at our center and had a high mortality rate. Because the mortality rate is so high, determining which factors are predictors is less important. A high proportion of patients had consumed ATT empirically, which could have been prevented.
authors.affiliation: Departments of GastroenterologyAll India Institute of Medical Sciences, New Delhi, India.
authors.forename: Ramesh
authors.initials: R
authors.lastname: Kumar
authors.forename: Vikram
authors.initials: V
authors.lastname: Bhatia
authors.forename: Shankar
authors.initials: S
authors.lastname: Khanal
authors.forename: V
authors.initials: V
authors.lastname: Sreenivas
authors.forename: S Datta
authors.initials: SD
authors.lastname: Gupta
authors.forename: Subrat K
authors.initials: SK
authors.lastname: Panda
authors.forename: Subrat K
authors.initials: SK
authors.lastname: Acharya
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000995:Antitubercular Agents / Q000009:adverse effects*; D005260:Female; D016751:Hepatitis E / Q000150:complications; D006801:Humans; D007194:India / Q000453:epidemiology; D007538:Isoniazid / Q000009:adverse effects; D017114:Liver Failure, Acute / Q000139:chemically induced* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D011718:Pyrazinamide / Q000009:adverse effects; D012293:Rifampin / Q000009:adverse effects; D016896:Treatment Outcome
chemical_list: D000995:Antitubercular Agents; D011718:Pyrazinamide; D007538:Isoniazid; D012293:Rifampin