title: Three months of weekly rifapentine plus isoniazid is less hepatotoxic than nine months of daily isoniazid for LTBI.
abstract: METHODS
  Nine months of daily isoniazid (9H) and 3 months of once-weekly rifapentine plus isoniazid (3HP) are recommended treatments for latent tuberculous infection (LTBI). The risk profile for 3HP and the contribution of hepatitis C virus (HCV) infection to hepatotoxicity are unclear.
  
  
  OBJECTIVE
  To evaluate the hepatotoxicity risk associated with 3HP compared to 9H, and factors associated with hepatotoxicity.
  
  
  METHODS
  Hepatotoxicity was defined as aspartate aminotransferase (AST) >3 times the upper limit of normal (ULN) with symptoms (nausea, vomiting, jaundice, or fatigue), or AST >5 x ULN. We analyzed risk factors among adults who took at least 1 dose of their assigned treatment. A nested case-control study assessed the role of HCV.
  
  
  RESULTS
  Of 6862 participants, 77 (1.1%) developed hepatotoxicity; 52 (0.8%) were symptomatic; 1.8% (61/3317) were on 9H and 0.4% (15/3545) were on 3HP (P < 0.0001). Risk factors for hepatotoxicity were age, female sex, white race, non-Hispanic ethnicity, decreased body mass index, elevated baseline AST, and 9H. In the case-control study, HCV infection was associated with hepatotoxicity when controlling for other factors.
  
  
  CONCLUSIONS
  The risk of hepatotoxicity during LTBI treatment with 3HP was lower than the risk with 9H. HCV and elevated baseline AST were risk factors for hepatotoxicity. For persons with these risk factors, 3HP may be preferred.
authors.affiliation: Division of Tuberculosis Elimination, Centers for Disease Control and Prevention (CDC), Atlanta, Georgia, USA.
authors.forename: E E
authors.initials: EE
authors.lastname: Bliven-Sizemore
authors.affiliation: Division of Infectious Diseases, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
authors.forename: T R
authors.initials: TR
authors.lastname: Sterling
authors.affiliation: Division of Tuberculosis Elimination, Centers for Disease Control and Prevention (CDC), Atlanta, Georgia, USA.
authors.forename: N
authors.initials: N
authors.lastname: Shang
authors.affiliation: Division of Infectious Diseases, Veterans Affairs Medical Center, The George Washington University Medical Center, Washington DC, USA.
authors.forename: D
authors.initials: D
authors.lastname: Benator
authors.affiliation: Respiratory Epidemiology and Clinical Research Unit, Montreal Chest Institute, McGill University, Montreal, Quebec, Canada.
authors.forename: K
authors.initials: K
authors.lastname: Schwartzman
authors.affiliation: Division of Infectious Disease, Department of Medicine, University of Colorado and Denver Health Hospital, Denver, Colorado, USA.
authors.forename: R
authors.initials: R
authors.lastname: Reves
authors.affiliation: Division of Viral Hepatitis, CDC, Atlanta, Georgia, USA.
authors.forename: J
authors.initials: J
authors.lastname: Drobeniuc
authors.affiliation: Division of Tuberculosis Elimination, Centers for Disease Control and Prevention (CDC), Atlanta, Georgia, USA.
authors.forename: N
authors.initials: N
authors.lastname: Bock
authors.affiliation: Division of Tuberculosis Elimination, Centers for Disease Control and Prevention (CDC), Atlanta, Georgia, USA.
authors.forename: M E
authors.initials: ME
authors.lastname: Villarino
mesh_terms: D000328:Adult; D000995:Antitubercular Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001219:Aspartate Aminotransferases / Q000097:blood; D001938:Brazil; D002170:Canada; D016022:Case-Control Studies; D056486:Chemical and Drug Induced Liver Injury; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D006526:Hepatitis C / Q000150:complications; D006801:Humans; D007538:Isoniazid / Q000008:administration & dosage* / Q000009:adverse effects; D055985:Latent Tuberculosis / Q000150:complications / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D012293:Rifampin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D012307:Risk Factors; D013030:Spain; D014481:United States
chemical_list: D000995:Antitubercular Agents; D001219:Aspartate Aminotransferases; D007538:Isoniazid; D012293:Rifampin; C018421:rifapentine