Hepatotoxicity of tuberculosis chemotherapy under general programme conditions in Singapore.
METHODS
The Singapore Tuberculosis (TB) Control Unit, a high volume national referral centre.


OBJECTIVE
To determine the incidence, clinical course and outcome of TB drug-induced hepatitis (DH) and the risk factors associated with DH under general programme conditions.


METHODS
A retrospective review of adult patients started on TB treatment in 1998.


RESULTS
There were 55 cases of DH in the cohort of 1036 patients treated in 1998. The median time to diagnosis of DH was 38 days. Factors significantly associated with DH were abnormal baseline transaminases/ bilirubin (OR 2.1, 95%CI 1.1-4.3, P = 0.02), age >60 years (OR 1.97, 95%CI 1.14-3.34, P = 0.01) and female sex (OR 1.9, 95%CI 1.07-3.4, P = 0.02). Ethnicity, self-reported alcohol consumption and body weight were not associated with development of DH. All three patients with fatal DH had received pyrazinamide-containing regimens. Treatment was re-introduced in 48 patients and successfully completed in 45 patients. The median time to reinstitution of TB treatment was 23 days.


CONCLUSIONS
The incidence of TB drug-induced hepatitis was 5.3%. Age >60 years, abnormal baseline transaminase/bilirubin levels and female sex were risk factors associated with the development of TB drug-induced hepatitis.
Teleman
M D
MD
Department of Clinical Epidemiology, Tan Tock Seng Hospital, Singapore.
Chee
C B E
CB
Earnest
A
A
Wang
Y T
YT
D000410:Alanine Transaminase / Q000097:blood; D000995:Antitubercular Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001219:Aspartate Aminotransferases / Q000097:blood; D001663:Bilirubin / Q000097:blood; D056486:Chemical and Drug Induced Liver Injury / Q000453:epidemiology*; D015331:Cohort Studies; D005260:Female; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D011718:Pyrazinamide / Q000009:adverse effects / Q000627:therapeutic use; D012189:Retrospective Studies; D012307:Risk Factors; D012846:Singapore / Q000453:epidemiology; D013997:Time Factors; D014397:Tuberculosis, Pulmonary / Q000517:prevention & control*
D000995:Antitubercular Agents; D011718:Pyrazinamide; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D001663:Bilirubin