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

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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.
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Keywords: MDR-TB; Russia; Tomsk; drug-resistant tuberculosis; hepatitis; hepatotoxicity

Document Type: Research Article

Affiliations: 1: Program in Infectious Disease and Social Change, Department of Global Health and Social Medicine, Harvard Medical School, Boston, Massachusetts, USA; Division of Global Health Equity, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA; Partners In Health, Boston, Massachusetts, USA 2: Partners In Health, Boston, Massachusetts, USA 3: Division of Global Health Equity, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA; Partners In Health, Boston, Massachusetts, USA 4: Tomsk Oblast Tuberculosis Services, Tomsk, Russian Federation 5: Federal Penitentiary Services, Tomsk, Russian Federation 6: Division of Global Health Equity, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA 7: Case Western Reserve University, Cleveland, Ohio, USA 8: Program in Infectious Disease and Social Change, Department of Global Health and Social Medicine, Harvard Medical School, Boston, Massachusetts, USA

Publication date: 2012-05-01

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  • The International Journal of Tuberculosis and Lung Disease publishes articles on all aspects of lung health, including public health-related issues such as training programmes, cost-benefit analysis, legislation, epidemiology, intervention studies and health systems research. The IJTLD is dedicated to the continuing education of physicians and health personnel and the dissemination of information on tuberculosis and lung health world-wide.

    Certain IJTLD articles are selected for translation into French, Spanish, Chinese or Russian. They are available on the Union website

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