DECISION

DECOMPENSATED CIRRHOSIS: IDENTIFICATION OF NEW COMBINATORIAL THERAPIES BASED ON SYSTEM APPROACHES

Abstract

In 2013, cirrhosis was responsible for 1.2 million deaths worldwide. This mortality is due to cirrhosis decompensation, defined as development of ascites, hepatic encephalopathy, and/or gastrointestinal hemorrhage, and its progression to acute-on-chronic liver failure (ACLF). Patients with decompensated cirrhosis receive many treatments such as intravenous and oral absorbable antibiotics, oral non-absorbable antibiotics, albumin, proton-pump inhibitors, laxatives, diuretics, betablockers, vasoconstrictors, statins, anticoagulants, steroids and antiviral agents, but also invasive therapies like portosystemic shunting, artificial organ support and total plasma-exchange. Despite these multiple treatments, short term mortality of patients with decompensation of cirrhosis remains high (11% at day 28) because of large interindividual variability in precipitating events, in clinical presentation and in response to treatment. This clinical heterogeneity calls for treatment personalization according to underlying molecular mechanisms. The overall objective of the DECISION project is to enhance our systems level understanding of the pathophysiology of cirrhosis decompensation to highlight new combinations of therapies to eventually decrease patients’ mortality at 28 days. First, this project will improve our understanding of the pathophysiology of cirrhosis decompensation by integrating detailed clinical data with multi-omic profiling data. This project will take advantage of the prospective cohorts established by the EFClif including over 3300 patients with 4.350 available blood samples. Second, the combinations of therapies identified will be tested in murine models of decompensation of cirrhosis leading to ACLF to prevent occurrence of this syndrome and mortality. Third, the most promising combination of therapies will be tested in a clinical trial including patients with decompensation of cirrhosis, using ACLF or death at day 28 as the primary endpoint.

Project details

Unibo Team Leader: Paolo Caraceni

Unibo involved Department/s:
Dipartimento di Scienze Mediche e Chirurgiche

Coordinator:
Ef Clif - EUROPEAN FOUNDATION FOR THE STUDY OF CHRONIC LIVER FAILURE(Spain)

Other Participants:
Universitat De Barcellona (Spain)
Easl European Association For The Study Of The Liver (Switzerland)
Ucl University College London (United Kingdom)
European Liver Patients Association (Belgium)
Navarrabiomed-Fundacion Miguel Servet (Spain)
Cea-Commissariat A L'Energie Atomique Et Aux Energies Alternatives (France)
Assistance Publique - Hopitaux De Paris (France)
Università degli Studi di TORINO (Italy)
Servicio Madrileǹo De Salud (Spain)
Yh Youhealth Ab (Sweden)
Inserm (France)
Universitaetsklinikum Aachen (Germany)
Università  degli Studi di PADOVA (Italy)
Institut Catala De La Salut (Spain)
Concentris Research Management GmbH (Germany)
Nordic Bioscience A/S (Denmark)
Johann Wolfgang Goethe - Universitaet Frankfurt Am Main (Germany)
ALMA MATER STUDIORUM - Università di Bologna (Italy)
Erasmus Universitair Medisch Centrum Rotterdam (Netherlands)
Fundació Privada Clínic per a la Recerca Biomèdica (Spain)

Total Eu Contribution: Euro (EUR) 6.000.007,13
Project Duration in months: 66
Start Date: 01/04/2020
End Date: 30/09/2025

Cordis webpage
Project website

Good health and well-being This project contributes to the achievement of the Sustainable Development Goals of the UN 2030 Agenda.

UE flag This project has received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement No 847949