Liver fibrosis and Portal hypertension
Prof. Jonel Trebicka, Laboratory for Liver Fibrosis and Portal Hypertension, Dept of Internal Medicine, University of Bonn
In patients with chronic liver disease, portal hypertension and progressive fibrosis are concomitant pathological processes interacting with each-other and leading to severe complications. The mechanics of matrix and the distinct response of different hepatic cell types contribute in the development of liver injury and cancer. Moreover, cellular mechanics play a crucial role on the remodeling of matrix in chronic liver disease. Interruption of the liver injury either by treating the initial liver injury and addressing the perpetuating risk factors will improve both fibrosis and prevent or ameliorate portal hypertension. Currently, after the successful cure of viral hepatitis, lifestyle-related liver damage due to chronic alcoholism or morbid obesity will remain the main factor leading to liver fibrosis and portal hypertension. Even though, the basic pathogenetic mechanisms of development of fibrosis and portal hypertension are similar. Especially RhoA/Rho-kinase pathway is crucially involved in the pathogenetic processes inside and outside the liver. RhoA/Rho-kinase is crucial in mechanics of cells, and the modulation of these targets has been evaluated in different animal models. Also, some well-established drugs, which are used in humans for other indications (for example, statins), are promising if applied early and concomitantly to standard therapy. In the future, more cell-specific targeting and personalized strategies must be considered to avoid progression of disease and complications.