PURPOSE: To investigate the incidence of drug-induced hepatotoxicity(DIH) caused by anti-tuberculosis drugs and to identify the association of DIH and serum drug concentrations.
METHODS: Serum levels of isoniazid, rifampicin, ethambutol, pyrazinamide were analysed by blood sample two hours after drug ingestion in patients on anti-tuberculosis treatment. Hepatotoxicity of anti-tuberculosis drug was defined when serum aspartate aminotransferase(AST) or alanin aminotransferase(ALT) exceed three times upper limit of normal and examined retrospectively. We compared serum drug level and other clinical factors between hepatotoxicity group and no-hepatotoxicity group. Patients with human immunodeficiency virus co-infection, acute viral hepatitis, chronic liver disease, suspicious malabsorption (gastrointestinal disease, diarrhea) were excluded.
RESULTS: Between June 2006 and February 2010, 195 patients in one tertiary hospital were included in the analysis. The median age of 195 patients (men 60%) was 46 (range 16-92 yrs old). Bacteriologically confirmed pulmonary tuberculosis (TB) was diagnosed in 59% of patients and positive nontuberculous mycobacteria culture with or without TB were observed in 13.8%. Of the 195 patients, 19 (9.7%) experienced hepatotoxicity. Mean AST/ALT level of hepatotoxicity group was 245/244 respectively. Among 19 patients, eight patients showed pyrazinamide related hepatotoxcicity and nine patients experienced INH or RMP related hepatotoxicity and two subjects did not have anti-TB drug related event. However serum levels of four anti-TB drugs did not differ statistically between hepatotoxicity group and no-hepatotoxicity group. Age, sex, past history of TB, body mass index(BMI) also did not show statistical difference.
CONCLUSIONS: There were relatively small number of patients whose drug level exceeds reference range and their serum drug level did not show relevance to DIH.
CLINICAL IMPLICATIONS: Drug induced hepatotoxicity on current standard dose of anti-tuberculosis drugs may be idiosyncratic not dose dependent.
DISCLOSURE: The following authors have nothing to disclose: Ina Jeong, Junghan Song, Ho Il Yoon, Choon-Taek Lee, Jae-Ho Lee
No Product/Research Disclosure Information