Risk factors revealed for anti-tuberculosis drug hepatotoxicity

Dec 10 2012

By Liam Davenport, medwireNews Reporter

The risk for hepatotoxicity among patients treated with anti-tuberculosis (TB) drugs is affected by gender, ethnicity, and the presence of genetic polymorphisms, say Argentinean researchers.

They found that mutations that influence N-acetyltransferase 2 (NAT-2) acetylator status were linked to anti-TB drug-induced hepatoxicity (ATDH), as were female gender and being of Bolivian ethnic origin, reports the team, led by Gabriela de Larrañaga, from Hospital of Infectious Diseases 'F. J. Muñiz' in Buenos Aires.

They write in the Journal of Gastroenterology and Hepatology: "Given the increase in both TB cases and ATDH incidence levels, as well as the associated hospitalization costs in Buenos Aires, it may be necessary in the future to closely follow female TB patients and patients of Bolivian ethnicity during TB treatment.

"It may also be helpful to know the patients' acetylator status prior to or at the beginning of the TB treatment regimen."

The researchers studied 200 TB patients treated with anti-TB drugs, examining the allelic and genotypic frequency distribution of NAT-2 and cytochrome P450 2E1.

In all, 40% of the participants were female, 47.5% were Argentines, 40% were Bolivian, 8% were Peruvian, 3.5% were Paraguayans, and 1% were other nationalities. Comorbid diseases were present in 21% of patients, the most common being diabetes and a hepatitis C virus infection, seen in 3.5% and 3.0% of patients, respectively.

Of the 175 patients for whom complete data were available, 47 (26.9%) developed ATDH. Compared with patients who had ATDH, those without the complication were significantly more likely to be female. In addition, ATDH status was significantly associated with nationality and acetylator status.

Interestingly, there were no significant associations between the presence of ATDH and clinical measures, such as body mass index, malnutrition, TB localization, comorbid diseases, smoking, and drug abuse. The exception was alcohol abuse status, whereby alcoholism was significantly more common in individuals without ATDH.

Multivariate analysis revealed that slow acetylator status, female gender, and Bolivian ethnicity were independent variables that predicted hepatotoxicity associated with anti-TB drugs, at odds ratios of 2.62, 2.73, and 2.71, respectively.

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