Korean J Intern Med.  2016 Jan;31(1):65-72. 10.3904/kjim.2016.31.1.65.

Early monitoring for detection of antituberculous drug-induced hepatotoxicity

• Lee CM
• Lee SS
• Lee JM
• Cho HC
• Kim WS
• Kim HJ
• Ha CY
• Kim HJ
• Kim TH
• Jung WT
• Lee OJ

• KMID: 2373774
• DOI: http://doi.org/10.3904/kjim.2016.31.1.65

Abstract

BACKGROUND/AIMS
We investigated the time of onset of antituberculous drug-induced hepatotoxicity (ADIH) and related characteristics.
METHODS
Adult patients (n = 1,031) treated with first-line antituberculous drugs between February 2009 and January 2013 were enrolled.
RESULTS
Of the 1,031 patients, 108 patients (10.5%) developed ADIH a mean of 39.6 +/- 43.7 days after treatment initiation. Twenty-eight patients (25.9%) developed ADIH within 7 days, 73 (67.6%) within 30 days, and the rest after 30 days. The < or = 30-day group was characterized by higher peak alanine aminotransferase (ALT) level and a high proportion of patients with maintenance of first-line antituberculous drugs compared to the > 30-day group. In subgroup analysis, the < or = 7-day group was characterized by higher baseline aspartate aminotransferase and ALT, high proportion of patients with maintenance of first-line antituberculous drugs, and high proportion of patients with extrapulmonary tuberculosis compared to patients with ADIH that developed beyond 7 days. In multivariate analysis, serum ALT > 40 IU/L (odds ratio [OR], 2.995; 95% confidence interval [CI], 1.580 to 5.680; p = 0.001) and presence of anti-hepatitis C virus (OR, 4.204; 95% CI, 1.822 to 9.700, p = 0.001) were independent risk factors for development of ADIH.
CONCLUSIONS
Approximately 70% of the cases of ADIH occurred in the first month of antituberculous treatment, and were associated with continuation of the first-line drug regimen.

Keyword

Drug-induced liver injury; Drug monitoring; Tuberculosis; Republic of Korea

MeSH Terms

Adult
Aged
Alanine Transaminase/blood
Antitubercular Agents/*adverse effects
Aspartate Aminotransferases/blood
Biomarkers/blood
Chemical and Drug Induced Liver Injury/blood/*diagnosis/etiology
Chi-Square Distribution
Clinical Enzyme Tests
Coinfection
Drug Monitoring/*methods
Drug Therapy, Combination
Early Diagnosis
Female
Hepatitis/complications/diagnosis
Humans
*Liver Function Tests
Logistic Models
Male
Middle Aged
Multivariate Analysis
Odds Ratio
Predictive Value of Tests
Retrospective Studies
Risk Factors
Time Factors
Alanine Transaminase
Antitubercular Agents
Aspartate Aminotransferases
Biomarkers