Anti-Tubercular Drug-Induced Liver Injury: Current Understanding and Emerging Directions

Most common adverse effect causing cessation of anti-tubercular treatment (ATT) is drug-induced liver injury (DILI) which is unpredictable due to its idiosyncratic nature. ATT is the most common cause of DILI and drug-induced acute liver failure (ALF) in South East Asia. Spectrum of ATT-DILI ranges from asymptomatic raised transaminases to acute hepatitis to acute liver failure (ALF). ALF due to ATT has a more aggressive course with up to 70% mortality. Both modifiable and non-modifiable risk factors are involved. Increasing age, female gender, genetic predisposition, poor nutrition, underlying liver disease, and concomitant viral infections make one prone to ATT-DILI. Thus, pretreatment evaluation is very important. Diagnosis of ATT-DILI is challenging due to lack of specific diagnostic tests; rather, it is a diagnosis of exclusion. Mild transient asymptomatic raised transaminases is due to hepatic adaptation and does not require any modification or cessation of ATT. Early detection of clinically significant DILI by frequent monitoring is associated with better prognosis and low mortality. Prompt withdrawal of all the potential hepatotoxic drugs is the key step in the management. Since the benefit of first-line ATT outweighs the monitored risk, reintroduction is always considered after normalization of raised transaminases. Ideal regimen is sequential reintroduction with incremental dosage of least hepatotoxic drug first, but evidence for this is lacking. Since hepatotoxicity rate is similar across different regimens, reintroduction is individualized based on perceived clinical risk. Future research is needed to identify specific biomarker panel for diagnosing ATT-DILI.