Scientists finded a link between efavirenz and liver disease
Over the past 20 years, the world has appeared a lot of various drugs for the treatment of HIV infection, significantly changed the lives of patients for the better. However, until now the action of a number of them, in particular, NNIOT, has been associated with the risk of developing certain diseases, including liver disease. A new study, published in January in the Journal of Hepatology, made it possible to determine the relationship responsible for the undesirable side effects of the well-known and often prescribed PLHIV efavirenz.
Like all organisms, humans are exposed to the toxic effects of chemical compounds, which are mitigated by metabolic mechanisms. The x-receptor pregnane (PXR) plays an extremely important role in this process.
Considering that so far the key mechanisms that determine one of the most common side effects of ARV drugs - fat accumulation in the liver - have not been identified, Dr. Zhou and his colleagues tried to find out whether there is a link between the work of ARV drugs and PXR, affecting lipid levels.
Using both the animal model without changes (rodent) and the specially created “liver-specific” model of a PXR deletion mouse, experts in the course of the study found that efavirenz “included” PXR target genes both in vivo and in vitro, most stimulating the absorption of fatty acids and cholesterol synthesis depending on the dose. To confirm these results, scientists used a model of mice expressing human PXR instead of mouse PXR.
“These results provide a new understanding of the mechanism by which ARV therapy causes dyslipidemia, and identify potential treatment targets to mitigate the increased risk of cardiovascular diseases and liver diseases caused by efavirenz,” Zhou said.
Dr. Richard N. Greenberg, an infectious diseases specialist at the University of Kentucky, who also participated in the study, views the results as a guide for physicians and a basis for further development.
“Now that we have found a way to accumulate fat in the liver, we can look for useful applications, including possible treatments that can alleviate the side effects of PXR agonists, such as efavirenz,” the scientist said.
“In the meantime,” he adds, “clinicians should take into account [the results obtained - ed.] And be vigilant about their patients who are prescribed PXR agonists.”