Elevated serum aminotransferase induced by isoniazid in relation to isoniazid acetylator phenotype

Abstract

Of 143 patients with pulmonary tuberculosis receiving isoniazid therapy, 52 (36%) had a transient elevation in serum aminotransferases. Among 74 patients taking isoniazid, rifampicin and streptomycin, 35 (47%) had such an increase, while of 69 patients taking isoniazid, amino-salicylic acid and streptomycin, 17 (24%) did; this difference was significant. Isoniazid therapy could be continued in all patients with the abnormal test results. In 36 of the patients receiving isoniazid, rifampicin and streptomycin, isoniazid and its metabolites were studied in the serum and urine using high-performance liquid chromatography after the oral administration of 10 mg per kg of isoniazid. We had chosen for this test 18 patients with normal aminotransferase levels and 18 with abnormal levels. There were 14 rapid acetylators in the patients with abnormal aminotransferase levels and 7 rapid acetylators in the patients with normal levels; this difference was significant. These results indicate that liver dysfunction is more often caused by an isoniazid/rifampicin regimen, and patients who are rapid acetylators are more susceptible.

Quantitative rat liver function test by galactose single point method

“…The incidence of anti-tuberculosis drug-induced hepatitis ranges from 1% to 36%, depending on different regimens and definitions of hepatic injury (Yamamoto et al 1986, Wu et al 1990, Huang et al 2003. Of the various anti-tuberculosis regimens, INH is the main drug that causes hepatotoxicity (Mitchell et al 1976, Yamamoto et al 1986, Wu et al 1990, Lee 1995. We showed here, through the histopathological evaluation of INH-induced hepatotoxicity in rats, the hepatocellular disintegration and vacuolation in the centrilobular region, even though there was no evidence of liver cell necrosis throughout the whole course.…”

“…Thus, both plasma INH has been widely used as a medicine in the prophylaxis and treatment of tuberculosis. The incidence of anti-tuberculosis drug-induced hepatitis ranges from 1% to 36%, depending on different regimens and definitions of hepatic injury (Yamamoto et al 1986, Wu et al 1990, Huang et al 2003. Of the various anti-tuberculosis regimens, INH is the main drug that causes hepatotoxicity (Mitchell et al 1976, Yamamoto et al 1986, Wu et al 1990, Lee 1995.…”

Cytochrome P450 2E1 genotype and the susceptibility to antituberculosis drug-induced hepatitis

“…[2][3][4][5][6][7][8][9][10][11][12][13][14][15] The incidence of antituberculosis drug-induced hepatitis ranges from 1% to 36%, depending on different regimens and definitions of hepatic injury. [3][4][5][6][7][8][9][10][11][12][13][14][15] This hepatotoxicity is also the most prevalent drug-induced hepatic injury in Taiwan and many other countries, and its associated mortality is not rare. 10,[13][14][15][16][17] Alcohol consumption, advanced age, acetylator status, and existing chronic liver disease have been reported to increase the risk of antituberculosis drug-induced hepatitis.…”

“…10,[13][14][15][16][17] Alcohol consumption, advanced age, acetylator status, and existing chronic liver disease have been reported to increase the risk of antituberculosis drug-induced hepatitis. [3][4][5][6][7][8][9][10][11][12][13][14][15] However, the exact mechanism for this hepatotoxicity remains unclear.…”

“…[2][3][4][5][6][7][8][9][10][11][12][13][14][15] Metabolic intermediates of isoniazid, instead of isoniazid per se, are incriminated as the cause of hepatotoxicity. 3,4 Therefore, a better understanding of the metabolism of isoniazid may be of help in understanding the mechanisms underlying hepatotoxicity and obviate its occurrence.…”