A Comparison between Two Strategies for Monitoring Hepatic Function during Antituberculous Therapy

• Published in: American journal of respiratory and critical care medicine 2012-03, Vol.185 (6), p.653-659
• Main Authors: SINGANAYAGAM, Aran, SRIDHAR, Saranya, LALVANI, Ajit, WICKREMASINGHE, Melissa, MIN KON, Onn, DHARIWAL, Jaideep, ABDEL-AZIZ, Dalia, MUNRO, Kerry, CONNELL, David W, GEORGE, Peter M, MOLYNEAUX, Philip L, COOKE, Graham S, BURROUGHS, Andrew K
• Format: Article
• Language: English
• Subjects: Adult; Alanine Transaminase - blood; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Anorexia; Antitubercular Agents - adverse effects; Antitubercular Agents - therapeutic use; Biological and medical sciences; Chemical and Drug Induced Liver Injury - metabolism; Chemical and Drug Induced Liver Injury - prevention & control; Diseases of the respiratory system; Female; Follow-Up Studies; Hepatitis; Humans; Intensive care medicine; Liver; Liver Function Tests - standards; Male; Medical sciences; Middle Aged; Monitoring, Physiologic - standards; Observational studies; Patients; Practice Guidelines as Topic; Predictive Value of Tests; Prospective Studies; Radiotherapy. Instrumental treatment. Physiotherapy. Reeducation. Rehabilitation, orthophony, crenotherapy. Diet therapy and various other treatments (general aspects); Risk Factors; ROC Curve; Tuberculosis; Tuberculosis - drug therapy; Tuberculosis - metabolism; Uniforms
• ISSN: 1073-449X; 1535-4970
• DOI: 10.1164/rccm.201105-0850OC

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