Gastroenterology has published a clinical trial promoted and coordinated by Hospital Clínic – IDIBAPS where it is shown that the addition of simvastatin to standard therapy in patients with cirrhosis can lengthen their survival. The article is signed by, among others, Dr. Jaume Bosch, hepatologist at Clínic and head of the research team Liver hemodynamics and portal hypertension of IDIBAPS; Dr. Juan Carlos García-Pagán and Juan González-Abraldes, from the same research group, and Dr. Fernando Torres, director of the IDIBAPS medical statistics platform.
Hepatic cirrhosis is a disease with a high prevalence: it is estimated that in Europe and the United States there are 250 cases each year per 100,000 people. In Spain, between 1 and 2% of the population suffer from it, and it is more frequent among men over 50 years. This disease consists of the destruction of the vascular structure and tissues of the liver, which are replaced by fibrosis, scars and nodules.
Researchers have found that the administration of simvastatin, a drug used to control elevated cholesterol levels, lengthen survival in patients with cirrhosis if little progress have been made by the disease: “the beneficial effect of simvastatin” says Dr. Bosch, “it is difficult to manifest itself in very advanced stages of cirrhosis.”
Why does simvastatin contribute to improving the prognosis of cirrhotic patients? This is because of the ability to significantly reduce mortality linked to hemorrhagic recurrence and infections. The study has shown that although the drug cannot prevent bleeding or infection, it can attenuate its detrimental effects in the course of the disease.
“Our research group,” says Dr. Bosch, “had found that statins, the class of drugs to which simvastatin belongs, played a very important role in preventing ischemia-reperfusion injury“. That is, this medicine can decrease the cellular suffering of the liver when it decreases and restores the blood supply. “In addition,” recalled Dr. Bosch, “we had researched in the liver that statins also protected in septic shock, because they prevent or attenuate hepatic endothelial damage“.
From preclinical research to trials in patients
The path that has led to the demonstration of the positive effects of simvastatin was initiated from basic research, carried out exclusively with public funding, in the research team Liver hemodynamics and portal hypertension of IDIBAPS.
The results published in Gastroenterology are the result of many years of study on how to improve cirrhosis from efforts aimed at protecting endothelial cells. Basic research had shown that increased expression of the transcription factor KLF2, which encodes endothelial protective genes, helps to deactivate hepatic stellate cells. Simvastatin favors the increase of KLF2 and is therefore capable of returning the hepatic stellate cells, responsible for fiber production and increased intrahepatic vascular resistance, to its normal state.
Juan G. Abraldes, Candid Villanueva, Carles Aracil, Juan Turnes, Manuel Hernandez-Guerra, Joan Genesca, Manuel Rodriguez, Jose Castellote, Juan Carlos García-Pagán, Ferran Torres, Jose Luis Calleja, Agustin Albillos, Jaume Bosch.
Gastroenterology, 2016. DOI: http://dx.doi.org/10.1053/j.gastro.2016.01.004