Frequency and risk factors of hepatotoxicity of anti Tuberculous drugs

ABSTRACT

Hepatotoxicity is reported in patients using first-line anti-tuberculous drugs regimen, among them 6-12% die. Identifying the risk factors for developing hepatotoxicity would probably reduce morbidity and mortality associated with T.B management. To study the frequency and risk factors of hepatotoxic reactions in patients receiving firat-line anti-tuberculous drugs. In addition to determine the relation between acetylator phenotype and anti-tuberculous drug hepatotoxicity. Seventy seven patients consecutively presenting to Suez Chest Hospital with active T.B diseases [WHO criteria], who were eligible for anti- tuberculous regimens [WHO guidelines] were included. Child B or C cirrhotic patients or Child A with liver enzymes exceeding double the normal were excluded in addition patients suffering from chronic renal or cardiac disease, hypersensitivity to anti-tuberculous drugs or receiving potentially hepatotoxic medications for other reasons were also excluded. 1-Rate of hepatotoxic reactions according to the diagnostic criteria. 2- Rates of fast and slow acetylator phenotypes. 3- Rate of risk factors among patients with hepatotoxicity versus patients without hepatotoxicity. Hepatotoxic reactions have been diagnosed in seven [9.1%] patients. By univariate analysis, age over 60 years [p = 0.02], alcoholism [p = 0.02], extra-pulmonary tuberculosis [p = 0.02] and severe forms of tuberculosis [p = 0.03] were statistically significant risk factors. Fifty eight [75.3%] of the study sample were slow acetylators, while 8 [10.4%] were fast acetylators. Three out of the eight [37.5%] of fast acetylators and only [6.9%] of the slow acetylators developed hepatotoxicity [p = 0.03]. Logistic regression models showed that fast acetylator phenotype was the only significant [p = 0.04] risk factor for early hepatotoxicity. Alcoholism [p = 0.01] was a significant risk factor for late hepatotoxicity. Hepatotoxic reactions among patients receiving anti-tuberculous drugs remain a considerable problem. Two patterns of liver injury can be observed. The first occurs earlier and is associated with fast acetylator phenotype. The second occurs later and is associated with alcoholism and HCV infection