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

TY - JOUR

T1 - A comparison between two strategies for monitoring hepatic function during antituberculous therapy

AU - Singanayagam, Aran

AU - Sridhar, Saranya

AU - Dhariwal, Jaideep

AU - Abdel-Aziz, Dalia

AU - Munro, Kerry

AU - Connell, David W.

AU - George, Peter M.

AU - Molyneaux, Philip L.

AU - Cooke, Graham S.

AU - Burroughs, Andrew K.

AU - Lalvani, Ajit

AU - Wickremasinghe, Melissa

AU - Kon, Onn Min

PY - 2012/3/15

Y1 - 2012/3/15

N2 - 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.

AB - 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.

KW - Adult

KW - Alanine Transaminase/blood

KW - Antitubercular Agents/adverse effects

KW - Chemical and Drug Induced Liver Injury/metabolism

KW - Female

KW - Follow-Up Studies

KW - Humans

KW - Liver Function Tests/standards

KW - Male

KW - Middle Aged

KW - Monitoring, Physiologic/standards

KW - Practice Guidelines as Topic

KW - Predictive Value of Tests

KW - Prospective Studies

KW - ROC Curve

KW - Risk Factors

KW - Tuberculosis/drug therapy

U2 - 10.1164/rccm.201105-0850OC

DO - 10.1164/rccm.201105-0850OC

M3 - Article

C2 - 22198973

SN - 1073-449X

VL - 185

SP - 653

EP - 659

JO - American Journal of Respiratory and Critical Care Medicine

JF - American Journal of Respiratory and Critical Care Medicine

IS - 6

ER -