Liver cirrhosis is a very common chronic disease and one of the leading causes of death in European. Moreover, cirrhosis has a marked impact in patients quality of life and represents a major burden for health systems. Treatment of cirrhosis is currently based on symptomatic management of complications and has not changed substantially in the last 20 years. There is an unmet need for therapies that target the pathobiology of cirrhosis. The objective of LIVERHOPE project is to evaluate a novel therapeutic strategy for patients with cirrhosis based on a combination of rifaximin and simvastatin, targeting the main pathophysiological mechanisms of disease progression , namely the impairment in the gut-liver axis and the persistent hepatic and systemic inflammatory response. This dual therapeutic approach is supported by preclinical data showing excellent and very promising results. We will perform two randomized double-blind trials to investigate safety, tolerability and efficacy of combination of simvastatin plus rifaximin in patients with decompensated cirrhosis in 5 EU countries (285 patients will be enrolled in two trials in DE, ES, FR, IT, UK). The expected impact is to halt progression to acute-on-chronic liver failure, the main cause of death, to decrease complications of the disease, to reduce hospital readmissions, to improve cost-effectiveness of therapy. Our final aim is to improve patients quality-of-life and increase survival as patients‘ care is the core of LIVERHOPE. Within the project we will also investigate biomarkers of response to treatment and disease progression that can be useful in clinical practice for improving the treatment of patients. We will invest our effort also in communication and dissemination activities for increasing awareness about chronic liver diseases in European countries so that preventive measures can be established to decrease the burden of cirrhosis and reduce social stigmatization of patients with chronic liver diseases.