Hepatotoxicity during treatment for multidrug-resistant tuberculosis: occurrence, management and outcome

Abstract

Setting: Multidrug-resistant tuberculosis (MDR-TB) treatment program in Tomsk, Russia.

Objective: To describe the incidence and management of hepatotoxicity during treatment of MDR-TB, and to assess risk factors associated with its development and impact on treatment outcomes.

Design: A retrospective case series performed among 608 patients.

Results: Hepatotoxicity, using American Thoracic Society (2006) definitions, was observed in 91/568 patients (16.5%). The median time to the first hepatotoxic event was 196 days post treatment commencement. Baseline factors associated with hepatotoxicity included elevated alanine aminotransferase/aspartate aminotransferase/bilirubin (OR 53.9, 95%CI 6.30-438.7), and renal insufficiency (OR 19.6, 95%CI 2.71-141.6). High treatment adherence (OR 3.25, 95%CI 2.07-5.09) and starting treatment in prison (OR 1.77, 95%CI 1.04-3.01) were associated with treatment success. Smoking (OR 0.44, 95%CI 0.21-0.92) and bilateral cavitary disease (OR 0.51, 95%CI 0.34-0.77) were associated with worse outcomes. For alcohol users, developing hepatotoxicity was associated with better outcomes (OR 4.40, 95%CI 1.79-10.81) than not (OR 0.42, 95%CI 0.25-0.68). One or more medications were permanently stopped in 10/91 patients, but in no case was treatment entirely discontinued.

Conclusion: MDR-TB treatment in the face of hepatotoxicity during therapy did not result in a statistically significant increase in poor outcomes.