title: Hepatitis associated with prothionamide for treatment of multidrug-resistant tuberculosis.
abstract: Timely and intensive monitoring for, and management of, adverse effects caused by anti-tuberculosis drugs are essential components of control programs for multidrug-resistant tuberculosis (MDR-TB). This retrospective case series was conducted in northern Taiwan from January 2007 to December 2008 at Taipei Medical University-Wan Fang Hospital, a 750-bed tertiary-care center and MDR-TB referral center. Hepatitis associated with prothionamide was defined as the recurrence of hepatitis after a second prothionamide treatment re-challenge. In total, 47 patients with MDR-TB enrolled in the Directly Observed Therapy, Short Course-Plus Program were identified during the study period, and 44 (93.6%) were treated with prothionamide. Seven of these 44 patients (15.9%) developed hepatitis after being treated with prothionamide concurrent with other anti-tuberculosis agents. Hepatitis associated with prothionamide occurred in three of these seven patients (6.8%). In these three patients, hepatitis developed following treatment with prothionamide for 28 days, 39 days or 45 days. Hepatitis developed rapidly after re-challenge with prothionamide at 4 days, 4 days and 3 days, respectively. Liver function returned to the normal range after cessation of prothionamide treatment for 19 days, 27 days or 28 days. Close monitoring of liver function was necessary in MDR-TB patients who received prothionamide treatment.
authors.affiliation: Department of Internal Medicine, Taipei Medical University-Wan Fang Hospital, Taiwan.
authors.forename: Han-Lin
authors.initials: HL
authors.lastname: Hsu
authors.forename: Kuan-Jen
authors.initials: KJ
authors.lastname: Bai
authors.forename: Yi-Chun
authors.initials: YC
authors.lastname: Chiang
authors.forename: Shian-Jiun
authors.initials: SJ
authors.lastname: Lin
authors.forename: Ming-Chih
authors.initials: MC
authors.lastname: Yu
mesh_terms: D000995:Antitubercular Agents / Q000008:administration & dosage / Q000009:adverse effects; D001663:Bilirubin / Q000097:blood; D056486:Chemical and Drug Induced Liver Injury / Q000097:blood / Q000517:prevention & control; D016903:Drug Monitoring; D006801:Humans; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000472:pathogenicity; D011515:Prothionamide / Q000008:administration & dosage / Q000009:adverse effects*; D012189:Retrospective Studies; D013624:Taiwan; D000637:Transaminases / Q000097:blood; D018088:Tuberculosis, Multidrug-Resistant / Q000188:drug therapy* / Q000382:microbiology; D014397:Tuberculosis, Pulmonary / Q000188:drug therapy* / Q000382:microbiology; D028761:Withholding Treatment
chemical_list: D000995:Antitubercular Agents; D011515:Prothionamide; D000637:Transaminases; D001663:Bilirubin