A comparison between two strategies for monitoring hepatic function during antituberculous therapy

Aran Singanayagam, Saranya Sridhar, Jaideep Dhariwal, Dalia Abdel-Aziz, Kerry Munro, David W. Connell, Peter M. George, Philip L. Molyneaux, Graham S. Cooke, Andrew K. Burroughs, Ajit Lalvani, Melissa Wickremasinghe (Lead / Corresponding author), Onn Min Kon (Lead / Corresponding author)

    Research output: Contribution to journalArticlepeer-review

    32 Citations (Scopus)

    Abstract

    RATIONALE: The optimum strategy for monitoring liver function during antituberculous therapy is unclear.

    OBJECTIVES: To assess the value of the American Thoracic Society risk-factor approach for predicting drug-induced liver injury and to compare with a uniform policy of liver function testing in all patients at 2 weeks.

    METHODS: We conducted an observational study of adult patients undergoing therapy for active tuberculosis at a tertiary center. All patients had alanine transferase measurement at baseline and 2 weeks following commencement of therapy. Sensitivity, specificity, and positive and negative predictive values were used to assess strategies.

    MEASUREMENTS AND MAIN RESULTS: There were 288 patients included, and 21 (7.3%) developed drug-induced liver injury (57.1% "early" at 2 wk and 42.9% "late," after 2 wk). There were increased rates of individuals with HIV infection in the early drug-induced liver injury group compared with no drug-induced liver injury and late drug-induced liver injury groups (33% vs. 7.1% vs. 0%; P = 0.004). The American Thoracic Society algorithm had a sensitivity and specificity of 66.7 and 65.6%, respectively, for prediction of early and 22.2% and 63.7% for late drug-induced liver injury. The uniform monitoring policy had poor sensitivity but better specificity (22.2 and 82.1%) for prediction of late drug-induced liver injury.

    CONCLUSIONS: In our urban, ethnically diverse population, a risk-factor approach is neither sensitive nor specific for prediction of drug-induced liver injury. A uniform policy of liver function testing at 2 weeks is useful for prompt identification of a subgroup who develop early drug-induced liver injury and may offer better specificity in ruling out late drug-induced liver injury.

    Original languageEnglish
    Pages (from-to)653-659
    Number of pages7
    JournalAmerican Journal of Respiratory and Critical Care Medicine
    Volume185
    Issue number6
    DOIs
    Publication statusPublished - 15 Mar 2012

    Keywords

    • Adult
    • Alanine Transaminase/blood
    • Antitubercular Agents/adverse effects
    • Chemical and Drug Induced Liver Injury/metabolism
    • Female
    • Follow-Up Studies
    • Humans
    • Liver Function Tests/standards
    • Male
    • Middle Aged
    • Monitoring, Physiologic/standards
    • Practice Guidelines as Topic
    • Predictive Value of Tests
    • Prospective Studies
    • ROC Curve
    • Risk Factors
    • Tuberculosis/drug therapy

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