Hepatic Adverse Effects of Anti-Mycobacterium Tuberculosis Drugs and Their Associations with Various Genetic Variants

Abstract

Tuberculosis is a significant healthcare burden, especially in the developing world. Current first-line therapies for tuberculosis treatment (isoniazid, pyrazinamide, rifampicin, and ethambutol) have significant efficacy but they all have the potential to cause hepatotoxicity. Effects produced by these drugs may be asymptomatic with increased levels of aminotransferases in some patients or the development of severe hepatotoxicity in others. On the other hand, it can also lead to hepatic failure in some patients. In this review, we evaluated the studies on genetic variants showing associations with drug-induced hepatic injury in tuberculosis patients. Several studies on important genes such as NAT2, AADAC, CYP2E1, HLA, CYP7A1, ALDH1A1, NFkB, PXR, HMOX1, SLCO1B1, UGT1A1, NRF2, and MAFF were reviewed and discussed for utilizing them as predictors of hepatic injury in tuberculosis patients. Recommendations are made on the potential of some of these genetic variants as a screening tool for determining patients most likely to experience hepatic adverse effects after receiving standard first-line anti-mycobacterial tuberculosis treatment.