NAT2 Genotype-Guided INH Dosage to Reduce Drug-Induced Liver Injury in Thai Patients

Abstract

Sanchat Thanyanuch42984*, Chuchottaworn Charoen42985, Mahasirimongkol Surakameth42986 and Wattanapokayakit Sukanya42987

Background: The Slow Acetylator (SA) was associated with a higher risk of Anti-Tuberculosis Drug-Induced Liver Injury (AT-DILI). This study aimed to evaluate whether a lower dose of Isoniazid than that allocated in the conventional treatment, can reduce the incidence of AT-DILI in Thai SA patients.

Methods: The Tuberculosis patients were screened for NAT2 gene. The SA patients were recruited in an open-label, Randomized Control Trial and randomly assigned in a 1:1 ratio to receive an adjusted or the standard Isoniazid (INH) dose in the first-line regimen. The primary outcome was the AT-DILI incidence.

Results: Among 260 patients undergoing the NAT2 gene screening, the frequencies of the NAT2 acetylator were 37.30%, 49.62% and 13.08% for Slow, Intermediate and Rapid Acetylators respectively. 22 of 23 (95.65%) SA patients were included in the Intention- To-Treat analysis. No significant difference in the AT-DILI incidence between the two groups were found: 8.33% in the adjusted INH dose group vs. 18.18% in the standard dose INH group, P-value=0.5.

Conclusion: This study demonstrated that the lower dose of INH in Tuberculosis treatment in the SA patients did not reduce the risk of AT-DILI, the application of NAT2 gene for a guided dosage of INH should be further investigate.