Study of the vascular alterations in the pathophysiology of Non-Alcoholic Steatohepatitis and of the reciprocal causal role of Non-Alcoholic Steatohepatitis in cardiovascular disease.

Non-Alcoholic Fatty Liver Disease (NAFLD), the accumulation of fat droplets in the liver that is not related to alcohol consumption, is the most common chronic liver disease. It is associated with overweight/obesity, diabetes and blood lipid disturbances, all taking epidemic proportions. It can lead to severe liver disease and is predicted to become the most important indication for liver transplantation by 2020. It also has consequences outside the liver: in NAFLD the liver presumably releases substances that cause damage to the blood vessels or alters their function, causing cardiovascular disease (CVD). NAFLD hence increases significantly the risk of developing CVD, as well as the risk of diabetes and non-liver malignancies. The mechanisms by which NAFLD causes CVD is not well understood, as well as the mechanisms that cause NAFLD itself. We previously demonstrated that changes in structure and function of the blood vessels within the liver are altered early in NAFLD development. We also unraveled some of the mechanisms that link NAFLD to the development of CVD. The current project builds on this work and aims at further studying the mechanisms that explain the changes in the liver blood vessels as a causal mechanism in the development of NAFLD as well as the mechanisms linking NAFLD to CVD. These aspects will be studied in animal models and in a large patient cohort with baseline and follow-up metabolic, hepatological and cardiological phenotypical characterisation.

Keywords:CARDIOVASCULAR DISORDERS, LIVER DISEASE

Disciplines:Cardiology, Hepatology, Metabolic diseases