Scientists at research center Applied Medicine (CIMA) of the University of Navarra have discovered the molecular mechanism of an already known combination treatment of two substances that ameliorates primary biliary cirrhosis. In summary, they have described the role of the AE2 protein when combining ursodeoxycholic bile acid (UDCA) and glucocorticoids. The findings have just been published in The Journal of Clinical Investigation.

The origin of primary biliary cirrhosis, which mainly affects middle-aged women, is currently unknown. This pathology is associated with autoimmunity phenomena, damages the bile ducts of the liver and reduces bile production. In Spain more than 1,000 cases are diagnosed each year and the total number of patients exceeds 15,000 at issue . Dr. Juan Francisco Medina, director of the laboratory of Genetics Molecular CIMA, explains that at present "the diagnosis of the disease, usually early, allows early initiation of treatment with UDCA, which is usually very effective in more than half of the patients. There remain almost 40% of patients who do not respond satisfactorily to UDCA monotherapy. We have therefore sought and found the explanation why the combination of UDCA with glucocorticoids is promising in this subgroup of patients. Patients affected by this cirrhosis subject have a deficit of AE2, which is the protein manager of bicarbonate secretion in the bile".

Possibility of more cures with fewer transplants

The novelty of the recently published research consists in linking for the first time the combined treatment of UDCA and glucocorticoids with an increased amount of bicarbonate in bile and an improvement in bile production by the liver. Specifically, experiments in animal models and in cell culture demonstrate that "only the combined treatment of UDCA and glucocorticoids increases gene expression of the human AE2 protein in the liver."

With the known data , Dr. Medina considers it advisable to use combined treatment in cases with poor response to UDCA monotherapy. He proposes using a corticosteroid such as budesonide, with fewer side effects than cortisone and prednisone: "If for fear of side effects we allow the disease to progress, it is very likely that the only remedy will be transplantation. Conversely, if this pathway is confirmed as successful, it could reduce the issue number of transplants needed to save patients' lives."

The research published in The Journal of Clinical Investigation is the work of the CIMA team at the University of Navarra led by Dr. Medina and also composed of Fabián Arenas, Isabel Herviás, Miriam úriz, Ruth Joplin and Jesús Prieto.