title: Inactive hepatitis B surface antigen carrier state and hepatotoxicity during antituberculosis chemotherapy.
abstract: OBJECTIVE
  To determine whether inactive hepatitis B surface antigen (HBsAg) carriers are at a higher risk of drug-induced hepatotoxicity than control subjects during antituberculosis treatment with standard short-course regimens of isoniazid, rifampin, ethambutol, and/or pyrazinamide.
  
  
  METHODS
  Retrospective case-control study.
  
  
  METHODS
  Tertiary university medical center.
  
  
  METHODS
  One hundred ten inactive HBsAg carriers with newly diagnosed active tuberculosis who had been treated with isoniazid, rifampin, ethambutol, and/or pyrazinamide were included in the study population. Inactive HBsAg carriers were defined as follows: (1) positive for HbsAg; (2) negative for hepatitis B e antigen (HBeAg), positive for antibody to HBeAg; (3) < 10(5) copies per mL of serum hepatitis B virus DNA; and (4) normal pretreatment aspartate aminotransferase (AST)/alanine aminotransferase (ALT) levels. Ninety-seven HBsAg-negative patients who received standard antituberculosis medication were selected as control subjects.
  
  
  RESULTS
  The baseline characteristics of the 110 inactive HBsAg carriers were similar to those of the 97 noncarriers. A total of 85% of persons in both groups had received an initial treatment regimen that included pyrazinamide. Thirty-eight inactive HBsAg carriers (35%) and 19 control subjects (20%) exhibited elevated liver enzyme levels during antituberculosis treatment (p = 0.016). Drug-induced hepatotoxicity, which was defined as a liver transaminase level of >/= 120 IU/L, occurred more frequently in HBsAg carriers (9 of 110 carriers; 8%) than in control subjects (4 of 97 control subjects; 4%), although this was not a statistically significant discrepancy (p = 0.230). More importantly, HBsAg carriers (n = 9; 8%) who received antituberculosis therapy evidenced a higher proportion of moderate-to-severe drug-induced hepatotoxicity when compared with the control subjects (n = 2; 2%; p = 0.05). Isoniazid and rifampin were reintroduced as therapy after AST/ALT levels returned to baseline values in 10 patients (6 HBsAg carriers and 4 control subjects) among the 13 patients exhibiting drug-induced hepatotoxicity, and these retrials proved to be successful in 7 patients (5 HBsAg carriers and 2 control subjects).
  
  
  CONCLUSIONS
  Tuberculosis treatment in HBsAg-positive and HBeAg-negative inactive carriers could be pursued in the usual manner, using standard short-course regimens of isoniazid, rifampin, ethambutol, and/or pyrazinamide, with the condition that monthly liver function tests are performed.
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon-Dong, Kangnam-Ku, Seoul 135-710, Korea. wjkoh@smc.samsung.co.kr
authors.forename: Byoung Hoon
authors.initials: BH
authors.lastname: Lee
authors.forename: Won-Jung
authors.initials: WJ
authors.lastname: Koh
authors.forename: Moon Seok
authors.initials: MS
authors.lastname: Choi
authors.forename: Gee Young
authors.initials: GY
authors.lastname: Suh
authors.forename: Man Pyo
authors.initials: MP
authors.lastname: Chung
authors.forename: Hojoong
authors.initials: H
authors.lastname: Kim
authors.forename: O Jung
authors.initials: OJ
authors.lastname: Kwon
mesh_terms: D000328:Adult; D000995:Antitubercular Agents / Q000009:adverse effects*; D002353:Carrier State; D016022:Case-Control Studies; D056486:Chemical and Drug Induced Liver Injury / Q000453:epidemiology / Q000209:etiology*; D004977:Ethambutol / Q000009:adverse effects; D005260:Female; D006509:Hepatitis B / Q000097:blood; D006514:Hepatitis B Surface Antigens / Q000097:blood*; D006801:Humans; D015994:Incidence; D007538:Isoniazid / Q000009:adverse effects; D008297:Male; D011718:Pyrazinamide / Q000009:adverse effects; D012189:Retrospective Studies; D012293:Rifampin / Q000009:adverse effects; D012307:Risk Factors
chemical_list: D000995:Antitubercular Agents; D006514:Hepatitis B Surface Antigens; D011718:Pyrazinamide; D004977:Ethambutol; D007538:Isoniazid; D012293:Rifampin