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

Am J Respir Crit Care Med. 2012 Mar 15;185(6):653-9. doi: 10.1164/rccm.201105-0850OC. Epub 2011 Dec 28.

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alanine Transaminase / blood
  • Antitubercular Agents / adverse effects
  • Antitubercular Agents / therapeutic use*
  • Chemical and Drug Induced Liver Injury / metabolism
  • Chemical and Drug Induced Liver Injury / prevention & control*
  • 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*
  • Tuberculosis / metabolism

Substances

  • Antitubercular Agents
  • Alanine Transaminase