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

¹ Tuberculosis and Chest Service, Centre for Health Protection, Dept of Health, Hong Kong, CHINA
² Tuberculosis and Chest Unit, Grantham Hospital, Hong Kong, CHINA

^* To whom correspondence should be addressed. E-mail: kc_chang{at}dh.gov.hk.

	Abstract

We conducted a nested case-control study to examine whether dosing schedules of standard pyrazinamide-containing anti-tuberculosis treatment (standard treatment) might affect hepatotoxicity.

We identified retrospectively all patients with hepatitis by biochemical criteria from a cohort of 3007 clinic patients who commenced anti-tuberculosis treatment from 1 January to 30 June 2001. Each case with hepatitis between one and nine weeks post-treatment was compared by conditional logistic regression analysis with two controls selected randomly from patients without hepatitis in the same period and matched by gender, age, and standard treatment. Impacts of gender 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 (HBsAg) carriage as the only risk factor (odds ratio 1.8, 95% confidence interval (CI) 1.1-3.1). Logistic regression analysis showed that gender was non-significant but aging increased odds of hepatitis. The risk of hepatitis (95% CI) increased from 2.6% (1.9-3.5%) to 4.1% (3.2-5.3%) as age exceeded 49 years.

Dosing schedules in the first nine 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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