Inactive hepatitis B surface antigen carrier state and hepatotoxicity during antituberculosis chemotherapy.
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.
Lee
Byoung Hoon
BH
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
Koh
Won-Jung
WJ
Choi
Moon Seok
MS
Suh
Gee Young
GY
Chung
Man Pyo
MP
Kim
Hojoong
H
Kwon
O Jung
OJ
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
D000995:Antitubercular Agents; D006514:Hepatitis B Surface Antigens; D011718:Pyrazinamide; D004977:Ethambutol; D007538:Isoniazid; D012293:Rifampin