DECISION Project: Advancing Treatment Strategies for Decompensated Cirrhosis
DECISION results and knowledge videos
ClustALL: Stratifying Decompensated Cirrhosis Patients
Emergency Granulopoiesis in Liver Failure: When the Immune System Goes into Chaos
Explained by Ferran Aguilar (European Foundation for the Study of Chronic Liver Failure)
Acute liver failure doesn’t only damage the liver — it disrupts the immune system at its core.
In this video, we explore how emergency granulopoiesis, the rapid production of immune cells during crisis, becomes dysregulated in liver failure. Using the analogy of a fire station releasing firefighters, we illustrate how the body’s emergency response system can spiral into a vicious cycle: liver injury triggers immune chaos, which in turn fuels further damage.
Our findings reveal that this defective emergency response is not simply an overreaction — it represents a profound shift in how the immune “factory” operates. Understanding these mechanisms opens the door to new strategies: not to silence the immune system, but to help it produce the right cells, at the right time.
Tiny Messengers, Big Impact: Large Extracellular Vesicles in Acute Liver Decompensation
Explained by Dr. Shantha Valainathan (Assistance Publique-Hôpitaux de Paris)
Acute decompensation (AD) of cirrhosis marks a critical and often life-threatening turning point for patients with advanced liver disease. Yet predicting who will deteriorate within the next 90 days remains a major clinical challenge.
In this video, we explore how Large Extracellular Vesicles (lEVs) — tiny “suitcases” released by stressed or damaged cells — may hold the key to better risk prediction. By analyzing the protein cargo of these circulating messengers in patients with acute decompensation, we identified a distinct three-protein signature derived from the liver, immune system, and kidney.
Importantly, when these protein levels were added to the established CLIF-C AD score, the ability to predict 90-day mortality improved significantly.
Our findings suggest that integrating molecular information from extracellular vesicles into clinical scoring systems could help physicians identify the most vulnerable patients earlier — ensuring timely and targeted care when every hour counts.
Epigenetic ‘Switches’ in Cirrhosis: How DNA Methylation Shapes Disease Progression
Explained by Dr. Estefanía Huergo Iglesias (NavarraBiomed)
Why do some patients with cirrhosis suddenly deteriorate, while others remain stable?
In this video, we explore how epigenetic changes, subtle molecular mechanisms that regulate gene activity, may help explain differences in disease progression.
Using the analogy of genes as lights in a house, we illustrate how DNA methylation, a small chemical tag added to DNA, acts like a switch that can turn genes on or off without altering the underlying genetic code.
By analyzing DNA methylation patterns in patients with acute decompensation of cirrhosis, we found that those with worse outcomes showed higher global DNA methylation, indicating a widespread shift in gene regulation. We also identified specific epigenetic changes near genes involved in inflammation, immune function, metabolism, and liver function.
These findings suggest that epigenetic regulation plays an important role in disease progression and may, in the future, support improved monitoring, risk assessment, and prediction of clinical outcomes.
When Immune Cells Run Empty 🪫 Single-Cell Insights in Liver Disease
Explained by Dr. Theresa Wirtz (RWTH Aachen)
What happens inside the body before patients with cirrhosis suddenly deteriorate? In this video, Dr. Theresa Wirtz explores how single-cell technologies help uncover early changes in immune function that precede clinical worsening in advanced liver disease. By analyzing thousands of individual immune cells from patients with acute decompensation of cirrhosis, the team identified a striking pattern: a specific group of immune cells, monocytes, shows a profound loss of energy production before organ failure becomes apparent. Their mitochondria, the cell’s power stations, are impaired, leaving these cells present but functionally compromised. Importantly, this signal was consistently observed across large patient cohorts and was associated with infections, disease progression, and reduced survival. These findings suggest that immune dysfunction in liver disease develops gradually at the level of cell metabolism. Understanding these mechanisms may help guide future therapeutic strategies aimed at preserving immune cell function and preventing progression to acute-on-chronic liver failure.
How biomarker connections help forecast acute-on-chronic liver failure
Explained by Dr. Cristina Lopez-Vicario (Fundació Clínic per la Recerca Biomèdica)
Cristina López-Vicario introduces her research findings on multi-omics approaches to chronic liver disease. This research is carried out within the DECISION project and will be presented at #EASLCongress 2024.
A Standardized Rapid Animal Model for MASLD/MASH with Translational Potential
Explained by Dr. Frank Uschner (Universitätsklinikum Münster)
Metabolic dysfunction–associated steatohepatitis (MASH), part of the MASLD spectrum, is a rapidly growing cause of chronic liver disease worldwide. As fat accumulates in the liver and inflammation progresses, patients may develop cirrhosis and life-threatening complications.
Despite the increasing burden of disease, therapeutic options remain extremely limited, with weight reduction currently the only effective intervention for many patients.
In this video, we present a novel, standardized animal model for MASH-cirrhosis developed within the DECISION project. Unlike traditional models, which often require long induction times and lack reproducibility, this model replicates key features of metabolic liver disease, including stearosis, inflammation, and liver damage, within approximately eight weeks.
International Liver Congress 2022
Patient representative Josip Kresović from the European Liver Patients’ Association (ELPA) asks Prof. Dr. Pierre-Emmanuel Rautou, the scientific coordinator of DECISION, questions about the project, its clinical implications, and potential complications. The interviews were conducted during the International Liver Congress (ILC) in London, United Kingdom, on 24 June 2022.
Where is the coordinating institution of this cirrhosis project located?
Will this project increase the 28-day survival rate after acute decompensation?
What happens if a patient does not respond to a new combinatorial therapy?
Interview with Prof. Dr. Sara Montagnese
In this brief Zoom interview, Dennis Cleff from concentris research management (concentris) takes on a patient’s perspective and interviews Prof. Dr. Sara Montagnese from the University of Padova (UNIPD) via Zoom about the symptoms of decompensated cirrhosis and what kind of help exists once a cirrhosis patient starts displaying symptoms of acute decompensation.