Researchers in Argentina have found that the risk for hepatotoxicity among patients taking antituberculosis drugs depends on gender, ethnicity, and genetic polymorphisms. A team of researchers—led by Gabriela de Larrañaga from the F. J. Muñiz Hospital for Infectious Diseases in Buenos Aires—studied 200 TB patients treated with antituberculosis drugs. The team examined the allelic and genotypic frequency distribution of N-acetyltransferase 2 (NAT-2) and cytochrome P450 2E1. Forty percent of the patients were female and 47.5 percent were Argentinian, 40 percent Bolivian, 8 percent Peruvian, 3.5 percent Paraguayan, and 1 percent other nationalities.
Of the 175 patients who completed the study, 47 developed antituberculosis drug hepatoxicity (ATDH). ATDH status was significantly associated with nationality and acetylator status. The team found that mutations that influence NAT-2 acetylator status were linked to ATDH as were gender and Bolivian ethnic origin. There were no significant associations between the presence of ATDH and clinical measures including body mass index, malnutrition, TB localization, comorbid diseases, smoking, and drug abuse. Alcohol abuse was significantly more common in individuals without ATDH. The researchers concluded that slow acetylator status, gender, and Bolivian ethnicity were independent variables that predicted hepatotoxicity associated with antituberculosis drugs.
The article “Sex, Ethnicity, and Slow Acetylator Profile Are the Major Causes of Hepatotoxicity Induced by Anti-tuberculosis Drugs,” was published prior to print in the Journal of Gastroenterology and Hepatology (DOI: 10.1111/jgh.12069).