Risk factors for hepatotoxicity from antituberculosis drugs: a case-control study.

Abstract

Background -Several risk factors for the development of hepatotoxicity during short course antituberculosis therapy have been suggested. A case-control study was undertaken to assess the role of age, sex, disease extent, nutritional status, past history of liver disease, infection with hepatitis viruses, acetylator status, and high alcohol intake as risk factors in the development of hepatotoxicity in patients with pulmonary tuberculosis receiving antituberculosis treatment. Methods -The cases comprised 86 consecutive patients who were diagnosed as having hepatitis induced by antituberculosis drugs and who were negative for any of the hepatitis markers (HAVIgM, HBsAg, HBc-IgM, and anti-HCV). The control group comprised 406 consecutive patients attending the chest clinic who completed antituberculosis treatment without developing hepatitis. The variables analysed were age, sex, body mass index (BMI), history of high alcohol intake, radiological extent of the disease, acetylator status, and serum proteins.Results -The cases were older and their serum albumin levels were lower than in the control group. High alcohol intake was more common among the cases, they had more extensive disease radiologically, and the proportion of slow acetylators was higher. No differences were observed between the two groups in the other risk factors analysed. Conclusions -Of the various risk factors analysed, only advanced age, hypoalbuminaemia, high alcohol intake, slow acetylator phenotype, and extensive disease were risk factors for the development of hepatotoxicity. The risk of hepatitis in the presence of one or more of these risk factors may be increased. (Thorax 1996;51:132-136)

A randomised Phase II trial to evaluate the toxicity of high-dose rifampicin to treat pulmonary tuberculosis

“…Similar conclusions were made in two other reports. 17,18 Patients infected with hepatitis B and hepatitis C (n ¼ 14) had no recorded increases in ALT value. However, the numbers are too small to allow any comment on safety.…”

Risk Factors of Hepatotoxicity During Anti-tuberculosis Treatment

“…In literature, there is a wide disparity in the reported incidence of ATT-induced hepatitis ranging from 2 to 39% [2,5]. The incidence has been reported to be higher in developing countries and factors such as acute or chronic liver disease, indiscriminate use of drugs, malnutrition and more advanced tuberculosis have been implicated [13,14]. The reported mortality from ATT-induced hepatitis after the development of jaundice varies from 4-12% [15].…”

“…While some papers have focused on genetic factors, such as HLA typing [8], Cytochrome P450 2E1 20 or acetylator status, [13] others have primarily studied clinical factors, as the present study. Some studies have reported that the risk of ATTinduced hepatitis increases with advancing age, the highest incidence being in individuals older than 50 years [14].…”

Genetic variation in carboxylesterase genes and susceptibility to isoniazid-induced hepatotoxicity

“…7 The incidence of INH-induced hepatotoxicity ranges from 1 to 36%, depending on different regimens, the population being treated and the definition of hepatic injury used. 8,9 Alcohol consumption, presence of HIV, advanced age and chronic liver disease have been reported to increase the risk of INH-induced hepatotoxicity. [10][11][12][13][14] N-acetyltransferase 2 (NAT2) is directly involved in INH metabolism, and genetic variation in the NAT2 gene has been reported to be a risk factor for INHinduced hepatotoxicity.…”