Hepatotoxicity during treatment for multidrug-resistant tuberculosis: occurrence, management and outcome
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.
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: 01 May 2012
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