Hepatotoxicity with antituberculosis drugs: the risk factors

ABSTRACT

To assess the severity and frequency of hepatotoxicity caused by different antituberculosis [ATT] drugs and to evaluate whether concurrence of risk factors influence the antituberculosis drug induced hepatotoxicity. This prospective cohort study was conducted in Medical Unit-V and OPD department of Civil Hospital Karachi from July 2004 to July 2005. A total of 339 patients diagnosed of active tuberculosis infection with normal pretreatment liver function were monitored clinically as well as biochemically. Their data were collected on proforma and patients were treated with Isonized, Rifampicin and Pyrazinamide. Duration after which derangement in function, if any, occurred and time taken for normalization was noted. Treatment was altered as needed, with exclusion of culprit drug. Finally data was analyzed by SPSS version 10.0. ATT induced hepatotoxicity was seen in 67 [19.76%] out of 339 patients. Females were more affected as compared to males [26.3% vs. 19.7%]. BMI [kg/m2] of 91% of diseased group were less than 18.5 [p<0.01] most of them were anemic having low albumin level suggestive of lean body mass. Hepatotoxicity was more severe in AFB smear positive patients. Concomitant use of alcohol, paracetamol and low serum cholesterol were proved as predisposing factors. Isoniazid [37 patients [55.21%], p<0.01] was the main culprit followed by Rifampicin [23 patients, 34.21%] and Pyrazinamide [7 patients, 10.5%]. Most of the patients [61%] developed the hepatotoxicity within two weeks of starting antituberculosis therapy with mild to moderate alteration in ALT and AST. ATT-induced hepatitis is significantly more frequent and more severe in patients with hepatotoxicity risk factors