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Standard anti-tuberculosis treatment and hepatotoxicity: do dosing schedules matter?

¹ Tuberculosis and Chest Service, Centre for Health Protection, Department of Health, and ² Tuberculosis and Chest Unit, Grantham Hospital, Hong Kong, China.

CORRESPONDENCE: K. C. Chang, Yaumatei Chest Clinic 2nd floor Yaumatei Jockey Club Polyclinic, 145 Battery Street, Kowloon, Hong Kong, China. Fax: 852 23743575. E-mail: kc_chang{at}dh.gov.hk

Keywords: Dosing schedules, hepatitis, hepatotoxicity, risk factors, treatment, tuberculosis

Received: July 9, 2006
Accepted August 28, 2006

A nested case–control study was conducted in order to examine whether dosing schedules of standard pyrazinamide-containing anti-tuberculosis (TB) treatment (standard treatment) might affect hepatotoxicity.

The present authors retrospectively identified all patients with hepatitis using biochemical criteria from a cohort of 3,007 clinic patients who commenced anti-TB treatment from January 1 to June 30, 2001. Each case with hepatitis between 1–9 weeks post-TB treatment was compared using conditional logistic regression analysis with two controls selected randomly from patients without hepatitis in the same period and matched by sex, age and standard treatment. Impacts of sex and age were examined by logistic regression analysis of cases and patients without hepatitis.

Hepatitis occurred in 167 patients, of whom 96 qualified as cases. A conditional logistic risk model identified hepatitis B surface antigen carriage as the only risk factor (odds ratio (95% confidence interval (CI)) 1.8 (1.1–3.1)). Logistic regression analysis showed that sex was nonsignificant but ageing increased the odds of hepatitis. The risk of hepatitis increased from 2.6% (1.9–3.5%) to 4.1% (3.2–5.3%) as age exceeded 49 yrs.

Dosing schedules in the first 9 weeks have little impact on hepatotoxicity. If patients at risk of both hepatitis and relapse receive standard treatment, daily dosing is preferable.

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