Tuberculosis is the leading cause of mortality in developing countries. Antitubercular treatment in India has been introduced since 1950s and has been engaged for more than 50 years. However, hepatotoxicity secondary to antitubercular therapy pose a significant challenge to its management. It has been observed that anti-tubercular drugs like isoniazid, rifampicin, and pyrazinamide are potentially hepatotoxic and their adverse reactions are dependent on dose or hypersensitivity. Hepatotoxicity caused by antitubercular drugs can occur within a few weeks of starting of an intensive phase and diagnostic criteria includes increased serum transaminase levels with its signs and symptoms. 

The difference in the incidence of anti-tubercular drug-induced hepatotoxicity is attributed to the changes in patient characteristics, regimen used, type of monitoring and the diagnostic criteria suggestive of hepatotoxicity. Various predisposing factors correlated to anti-tubercular drug-induced hepatotoxicity are advanced age, gender, nutritional status, alcohol intake, widespread tuberculosis, unselective use of various drugs, ethnic factors, chronic liver disease and concomitant infections. 

It has been observed that there are no evidence-based guidelines that are accessible for the management of these patients. Key management of hepatotoxicity is cessation of anti-tubercular drugs like isoniazid, rifampicin, and pyrazinamide and sequential reintroduction after normalization of biochemical markers of liver injury including serum transaminase (AST, ALT) levels. However, a study conducted by Koul, 2015; Lampertico et al., 2017 reported that patients with severe or prolonged hepatotoxicity can tolerate the reintroduction of rifampin and isoniazid, but pyrazinamide is hazardous. This has been corroborated by other studies that reported the recurrence of hepatotoxicity is associated with reintroduction with a full-dose regimen of pyrazinamide. 

While reintroducing antitubercular therapy, liver function tests should be monitored periodically for 2 weeks during the initiation phase to assess anti-tubercular tolerance, especially in patients with liver cirrhosis. Furthermore, prompt diagnosis, treatment, and recognition of the main factors responsible for drug-induced hepatotoxicity are crucial to avert hepatitis induced mortality. Additionally, educating patient is of utmost importance regarding the occurrence of symptoms and the significance of clinical and laboratory surveillance.

Source: Nair RS, Akhilesh K, James E. Anti-tubercular drugs, predisposing factors and management of drug-induced hepatotoxicity: A concise and up-to-date review. Int. J. Res. Pharm. Sci., 2020, 11(3), 3096-3104.