ANNUAL REPORT 2025
Contents
Strengthening global collaboration and scientific leadership
Why the study of chronic liver disease matters
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Our foundations and purpose
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Building global consensus in cirrhosis and organ failure
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We are shaping the future of chronic liver disease
Toward data-driven evidence in liver transplantation for ACLF
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The path forward
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Fostering international collaboration and scientific exchange
Our network
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Our research environment
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Consolidating our long-term vision for research excellence
Our progress
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Statement from our Director
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23
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EF CLIF moves to an iconic location in Barcelona
Our year in numbers
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A decade advancing translational liver research through public–private collaboration
Advancing translational research in advanced chronic liver disease
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12
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New appointments to the Governing Board
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Risk stratification in decompensated cirrhosis
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12
Establishment of the Strategic Advisory Board
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A new experimental model to advance ACLF research
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Research outputs
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30
Advancing clinical research in critical care for advanced liver disease
Supporting independent investigator-led research and innovation
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30
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Access to intensive care and treatment response in advanced liver disease
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Scientific publications and communications
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32
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Why the study of chronic liver disease matters
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2,
Importantly, precipitating events associated with short term
mortality among patients withACLF are not reflected in the conventional
prognostic models for organ allocation falling short in
prioritizing most severe patients with decompensated
cirrhosis for liver transplantation.
The alarming increase in obesity rates, harmful use of alcohol, and an aging population mean that liver
disease will become an even greater global health
concern over the next decade. Experts agree that the
major causes of liver disease (i.e., alcohol-related liver
disease, metabolic dysfunction-associated steatotic liver disease, and viral
hepatitis) are amenable to prevention and treatment
providing an opportunity to reduce the burden of
liver disease and save lives. There is an urgent need to
engage with policymakers and health authorities to
invest in preventive actions and surveillance as regards
chronic liver disease.
Because cirrhosis is a progressive disease, efficient treatment and management of patients with chronic liver disease are essential to improve patients’ survival rates and reduce the socioeconomic impact of the disease. It is remarkable to note that there have been no new, disease-modifying approaches to the treatment of chronic liver disease. Liver transplantation is the one treatment that has shown promise in improving patient survival by restoring essential functions where no alternative treatment of comparable effectiveness exists even for patients with severe acute-on-chronic liver failure (ACLF). A system for organ allocation that ensures equitable distribution continues to be an unmet medical need for patients with cirrhosis, and particularly those who progress into ACLF.
deaths worlwide due to liver disease
Cirrhosis is
Alcohol
15th
11th
leading cause of cirrhosis globally
leading cause of DALY
leading cause of deaths worldwide
HBV & HCV infections
Leading causes of
CIRRHOSIS
Overweight and obesity
Harmful use of alcohol
Our foundations and purpose
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To achieve this, we: Provide financial support for chronic liver disease research projects.Encourage participation in competitive research and innovation initiatives focused on translational advancements to improve clinical practice and early diagnosis.Develop and promote programs and activities to train healthcare professionals and researchers.Foster the dissemination of new knowledge about chronic liver disease. Guided by our mission and reflected in our current strategy, we advance knowledge and facilitate the translation of research into clinical practice, striving to improve care and enhance the quality of life for patients with chronic liver disease.
By funding and supporting cutting-edge research, we contribute to advance the understanding of chronic liver disease, develop lifesaving treatments, and improve patient care.
Our work goes beyond research—we engage with healthcare professionals, policymakers, scientists, and patients to drive innovation, inform clinical practice, and advocate for equitable access to care. Together, we aim to transform how chronic liver disease is managed, making a lasting impact for individuals, families, and communities worldwide. Our bylaws, as of 2015, state that our purpose is “to design, support, promote, and lead biomedical research studies and projects at a supranational level in the field of Health Sciences, particularly in the area of chronic liver failure”.
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We are shaping the future of chronic liver disease
The path forward
The journey into our vision will be guided by: Supporting collaborative projects, providing resources for high-impact research, and cultivating a culture of shared expertise and mentorship within the chronic liver disease research community. Conducting large-scale multicenter studies, partnering with international stakeholders, engaging liver patient communities, and advising policymakers on evidence-based standards and protocols.
We envision a thriving network of researchers and healthcare professionals across Europe, united in their pursuit of advancing knowledge on cirrhosis and its complications.
Our vision is to establish a global standard of care for decompensated cirrhosis and acute-on-chronic liver failure, informed by cutting-edge research and multidisciplinary collaboration.
We aspire to be a reference in driving innovation for the diagnosis, prognosis, and treatment of cirrhosis and acute-on-chronic liver failure. Our vision is a future where advanced tools and novel therapies significantly improve patient outcomes and quality of life.
Fostering cross-disciplinary collaboration, facilitating global knowledge exchange, and investing in the development and evaluation of innovative therapeutic and diagnostic solutions.
Our network
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Our global network of tertiary care hospitals, universities, and research centers brings together over 1,000 laboratory-based researchers, consultant physicians, intensivists, surgeons, nurses, and pathologists to carry out groundbreaking chronic liver disease research, ranging from translational studies to large-scale clinical trials.
Global projects
EASL-CLIF Consortium
ENTR-CLIF
96 centers in 22 countries
120 centers in 29 countries
23 centers in 7 countries
The Global Projects chapter offers the framework to promote research in cirrhosis around the world and brings the opportunity to strengthen connections between healthcare professionals across geographical borders.
The Grifols Chair promotes translational studies in centers across Europe and North America within the framework of the European Network for Translational Research- Chronic liver failure (ENTR-CLIF).
Leading researchers and highly qualified scientists at these centers help moving scientific discovery from the laboratory to patients faster.
Through the large-scale observational studies we fund, these centers contribute to help drafting clinical practice guidelines that improve healhtcare and patients' outcomes. The European Association for the Study of the Liver (EASL)-Chronic Liver Failure (CLIF) Consortium also provides the framework to initiate new research ideas and programs, and offers the next generation of scientists and research leaders unique opportunities to drive future research and innovation in the area of liver disease.
Our research environment
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Find out more about the EF CLIF database
Our progress
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Statement from our Director
The strong performance of the score likely reflected its ability to capture the presence and intensity of systemic inflammation. This publication also initiated collaborative discussions involving Jonel Trebicka, Joan Clària, Ferran Aguilar, and myself on simplifying the score to facilitate bedside implementation. The second original study analyzed whole-blood RNA-seq data obtained at hospital admission from 1260 patients with ADC. Supported by the EU-funded DECISION project, this work was the first to identify maladaptive emergency granulopoiesis as a distinctive endotype associated with both pre-ACLF and poor survival outcomes. These findings provided the basis for a collaborative project with GENFIT aimed at generating a whole-blood single-cell multiomic atlas, including single-cell profiling of circulating hematopoietic stem and progenitor cells in patients with ADC.
In 2025, we continued advancing one of our two primary missions: addressing critical gaps in knowledge regarding the mechanisms underlying the most severe forms of acutely decompensated cirrhosis (ADC), with the aim of identifying clinically actionable biomarkers and novel therapeutic targets. In this context, our researchers and staff scientists published two original translational studies made possible through the prospective collection of blood samples within the seminal EF CLIF-sponsored PREDICT and ACLARA studies in patients with ADC. The first study described a 28-gene signature (the CLIF-SIG score) capable of accurately distinguishing, among 700 patients with ADC, those with pre-acute-on-chronic liver failure (pre-ACLF) or ACLF from those without these conditions.
This year’s report highlights our continued progress in translational and clinical research, with new initiatives advancing our understanding of chronic liver disease.
Our progress
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Joan Clària, Cristina Sánchez-Garrido, and Ferran Aguilar should be commended for their active contributions to these discussions. In 2025, we also continued advancing our second primary mission: conducting clinical research. Three developments deserve particular mention. First, Paolo Angeli, on behalf of the European Association for the Study of the Liver (EASL)-CLIF Consortium, continued collaborating with representatives of the EASL-Baveno Consortium on the design of a large European prospective observational study aimed at characterizing the trajectory of patients with compensated cirrhosis and the different patterns of decompensation episodes. During the year, the study protocol and electronic case report form were finalized, responsibilities among stakeholders clarified, and efforts concentrated on securing financial support. Second, our collaboration with GENFIT expanded through a Steering Committee
In parallel, Joan Clària completed preclinical studies evaluating the efficacy of novel therapeutic approaches developed by GENFIT in experimental models of ACLF. In 2025, we also welcomed Zhujun Cao, MD, PhD, from Shanghai Jiao Tong University School of Medicine as a Visiting Scientist. His one-year stay represents the first step in a broader collaboration between EF CLIF and Ruijin Hospital focused on clinical and translational research in ADC, particularly on blood transcriptomic alterations associated with immune cell production across disease severity stages.
Discussions were also pursued with representatives of Boehringer Ingelheim to develop a translational research program in ADC focused on identifying novel biomarkers and clinically relevant patient endotypes. In this regard, Anna Bosch,
involving Jonel Trebicka, Javier Fernández, Paolo Angeli, and other members of our team. Together with GENFIT staff, the committee analyzed data from a large Komodo database to characterize the landscape of clinical phenotypes and clinical practice patterns in ADC across the United States. This collaboration resulted in abstracts accepted for oral and poster presentation at American Association for the Study of Liver Diseases (AASLD)’s The Liver Meeting®, representing the first step toward a series of collaborative scientific publications. Third, discussions involving GENFIT representatives, the U.S. Food and Drug Administration, Jonel Trebicka, Paolo Angeli, and myself led us to reconsider the conceptual framework traditionally used to design clinical trials in patients with severe ADC. While short-term mortality remains a critical endpoint, additional outcomes such as hospital discharge, days free from organ support, and incidence of nosocomial infections are increasingly recognized as
Our progress
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including active participation from EF CLIF investigators. In addition, Jonel Trebicka and I, together with investigators from the EASL-Baveno Consortium, co-authored a review article on the interaction between inflammation and portal hypertension in cirrhosis progression. This publication exemplifies the collaborative effort to overcome traditional conceptual silos separating inflammation and portal hypertension in the understanding of cirrhosis progression.
Nearly ten years ago, EF CLIF initiated the process that ultimately led to the ACLARA study across Latin America. Beyond its resulting scientific publication in 2023, this initiative continued generating important benefits in 2025. A major milestone was the appointment of Alberto Farias to the EF CLIF Governing Board, reflecting our commitment to sustaining a strong two-way collaboration with Latin American colleagues. This close relationship was further demonstrated by
clinically relevant. Addressing these questions became a strategic priority for us in 2025, with contributions from our research team and the Data Management Center led by Cristina Sánchez-Garrido and Eva Usón. During 2025, we have also contributed to the ongoing global harmonization of diagnostic criteria for organ failures and ACLF through three additional publications. One original article, developed in collaboration with colleagues from the Chinese Group on the Study of Severe Hepatitis B (COSSH) Consortium, evaluated the broader applicability of the China-CLIF framework across diverse etiologies and varying severities of ACLF using EF CLIF patient cohorts. Two further position papers, published under the auspices of the Asian Pacific Association for the Study of the Liver (APASL) and AASLD, further illustrated the international commitment to harmonization efforts,
the participation of Paolo Angeli, Chair of the EASL-CLIF Consortium, and myself in the official launch of the LATAM-CLIF Consortium on 14 October in Rio de Janeiro, Brazil. Additional evidence of this growing collaboration can be seen in recent EF CLIF publications that increasingly integrate Latin American and European authorship. Furthermore, Latin American researchers ranked among the top contributors to patient recruitment in the CHANCE study, whose first rounds of analyses were conducted by our Data Management Center team at the end of 2025.
Prof. Richard MoreauDirector of EF CLIF
Our progress
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Our year in numbers
Currently, we fund
We published
We enabled
We participated in
19 papers
n new ancillary studies
1 large-scale observational study
5 scientific events
16 of these in open access journals
by independent researchers
We made
We raised over
We received
We welcomed
204 followers
€1.5 M
€624,00
media appearances - that we know of
across social media channels
from donations
in EU funding
Click on interactive elements to read more.
Advancing translational research in advanced chronic liver disease
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Risk stratification in decompensated cirrhosis
Predicting which patients with decompensated cirrhosis will rapidly deteriorate remains one of the major challenges in hepatology, as conventional biomarkers often fail to accurately capture the severity of systemic inflammation and immune dysfunction driving disease progression. During the year, we have carried out complementary studies exploring transcriptomic and immune-based approaches to risk stratification. One study introduced the CLIF-SIG score, a gene expression-based tool capable of improving prediction of acute-on-chronic liver failure (ACLF) and severe outcomes beyond traditional inflammatory markers.
In parallel, another investigation identified maladaptive activation of emergency granulopoiesis and the expansion of immature neutrophils as key immune mechanisms associated with poor prognosis in decompensated cirrhosis. Together, these findings contribute to a more precise understanding of systemic inflammation in advanced chronic liver disease and support the development of personalized strategies for early diagnosis, prognostic assessment, and therapeutic intervention.
Advancing translational research in advanced chronic liver disease
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Linking neutrophil production to outcomes in decompensated cirrhosis
A large transcriptomic analysis identified a stress-induced blood immune signature associated with poor outcomes in patients with decompensated cirrhosis. The study showed that maladaptive activation of emergency granulopoiesis—driven by the IL-6–STAT3–C/EBPB axis and leading to increased production of immature and immunosuppressive neutrophils—characterises patients who develop acute-on-chronic liver failure (ACLF) within 28 days or die without liver transplantation within 90 days of hospital admission. These findings highlight a key immune mechanism underlying disease progression and point to new opportunities for early risk stratification and therapeutic intervention.
This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement no. 847949.
Read more on our website
Advancing translational research in advanced chronic liver disease
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A gene-based score to improve risk prediction in acutely decompensated cirrhosis
with most patients who progressed to ACLF already identified at admission. These findings highlight the potential of transcriptomic profiling to refine risk stratification, support clinical decision-making, and enable more precise patient selection and monitoring in future therapeutic trials.
A newly developed gene-based score provided a more accurate assessment of systemic inflammation in patients with acutely decompensated cirrhosis, enabling improved prediction of disease progression and severe complications. Based on the identification of immune cell-related gene expression patterns, the CLIF-SIG score outperformed conventional biomarkers such as white cell count and C-reactive protein in identifying patients at high risk, including those who develop acute-on-chronic liver failure. In a cohort of 700 hospitalized patients, the score demonstrated strong predictive performance across different etiologies, clinical triggers, and patient populations,
Read more on our website
Advancing translational research in advanced chronic liver disease
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A new experimental model to advance ACLF research
This refined preclinical model addresses a major gap in ACLF research and provides a valuable platform to investigate disease mechanisms and evaluate future therapeutic strategies.
New mouse model was developed and validated that successfully reproduces the systemic inflammation and multiorgan failure characteristic of acute-on-chronic liver failure (ACLF). By combining chemically induced cirrhosis with polymicrobial peritonitis, the model closely reflects the clinical features and heterogeneity observed in patients, including liver, kidney, brain, circulatory, respiratory, and coagulation dysfunction. Importantly, the study adapts EASL-CLIF-C clinical definitions for use in mice, enabling closer comparability between experimental findings and the human condition.
Read more on our website
Advancing clinical research in critical care for advanced liver disease
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challenging traditional assumptions regarding intensive care unit admission in patients with advanced liver cancer. Together, these findings support a more individualized and evidence-based approach to critical care, with the ultimate goal of improving survival and treatment opportunities in advanced liver disease.
Access to intensive care and treatment response in advanced liver disease
Managing critically ill patients with advanced liver disease remains one of the greatest challenges in hepatology, requiring timely therapeutic decisions and equitable access to intensive care. We contributed important evidence to guide critical care management in high-risk patient populations, including patients with cirrhosis, septic shock, and advanced hepatocellular carcinoma receiving immunotherapy. Through large international clinical studies, these efforts helped clarify the role and limitations of specific therapeutic interventions, such as hydrocortisone in septic shock, while also
Advancing clinical research in critical care for advanced liver disease
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Reassessing intensive care access in advanced liver cancer
A large international study challenged long-standing barriers to intensive care unit (ICU) admission for patients with advanced hepatocellular carcinoma (HCC) receiving immunotherapy. Traditionally considered poor candidates for critical care, many of these patients were shown to survive severe complications and successfully resume cancer treatment following ICU admission. The study showed encouraging short- and mid-term survival rates among patients admitted for severe immune-related adverse events or complications such as variceal bleeding. The findings highlight the evolving role of critical care in the era of immunotherapy and support a more individualized approach to ICU admission in patients with advanced liver cancer.
Read more on our website
Advancing clinical research in critical care for advanced liver disease
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New evidence on steroid therapy in cirrhosis and septic shock
These results provide important evidence to guide critical care management and refine therapeutic strategies in this high-risk patient population.
The SCOTCH trial, the largest randomized study conducted to date in patients with cirrhosis and septic shock, evaluated the efficacy of low-dose hydrocortisone in critically ill patients admitted to intensive care units. The study showed that hydrocortisone did not improve short-term survival or overall shock resolution in patients requiring low to moderate vasopressor support, while some adverse metabolic effects were more frequent in treated patients. Importantly, the findings identified the severity of liver disease, the presence of acute-on-chronic liver failure (ACLF), and timely administration of appropriate antibiotics as the main predictors of survival.
Read more on our website
Strengthening global collaboration and scientific leadership
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Building global consensus in cirrhosis and organ failure
practice more closely with intensive care standards. By establishing shared diagnostic thresholds and unified clinical definitions, this work represents an important step toward harmonizing ACLF research and clinical management worldwide.
We took part in an international panel of hepatologists and intensivists, contributing to the development of new consensus statements that establish standardized definitions for organ system failures and acute-on-chronic liver failure (ACLF) in patients with cirrhosis. This initiative addresses longstanding variability in diagnostic criteria across institutions and research groups, providing a common framework to improve patient care, enable comparison of clinical outcomes, and strengthen the design of future clinical research. The consensus defines failure across major organ systems and highlights infection and immune dysfunction as central drivers of ACLF, while aligning hepatology
Read more on our website
Strengthening global collaboration and scientific leadership
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Toward data-driven evidence in liver transplantation for ACLF
As final analyses progress, the CHANCE study is expected to provide important prospective evidence to guide liver transplantation strategies, improve risk stratification, and support fairer access to transplantation for patients with ACLF.
We hosted a strategic working meeting with the leadership and coordination teams of the CHANCE study to advance analyses supporting the study’s first core publication. Discussions focused on key clinical endpoints, including 1-year graft and patient survival following liver transplantation in patients with ACLF grade 2 or 3, compared with patients with decompensated cirrhosis without ACLF, as well as transplant-free survival in patients with ACLF who were not listed for liver transplantation. Additional analyses addressed post-transplant mortality, waiting-list outcomes, and the development of new prognostic and futility models to support clinical decision-making in critically ill patients.
Read more on our website
Strengthening global collaboration and scientific leadership
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Fostering international collaboration and scientific exchange
Hosting international talent to advance ACLF research
We welcomed Dr. Zhujun Cao from Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, China, for a one-year research stay in Barcelona. Working under the supervision of Prof. Richard Moreau, Dr. Cao is investigating the immunopathogenesis of acute-on-chronic liver failure (ACLF) using prospective cohorts and multi-omics approaches. His stay reflects the growing scientific collaboration between EF CLIF and Chinese research groups and highlights our commitment to fostering international scientific exchange, mentorship, and collaborative research in chronic liver disease.
Strengthening international collaboration and scientific exchange remained a central component of our mission throughout the year. Through initiatives such as the Visiting Scientist Program and support for emerging regional research networks, we continue fostering knowledge sharing, mentorship, and long-term scientific partnerships across the global chronic liver disease community. Together, these initiatives contribute to building a more connected, collaborative research environment in hepatology.
Read more on our website
Strengthening global collaboration and scientific leadership
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Supporting the next generation of chronic liver disease leaders
Through regular scientific discussions and guidance from senior investigators, the initiative aims to empower emerging leaders and stimulate innovative, clinically relevant research in hepatology.
The Inspiring and Writing Group welcomed eight new junior researchers, reinforcing our commitment to fostering collaboration, mentorship, and innovation in chronic liver disease research. Building on our landmark datasets and biobank, the group continues to provide a collaborative platform for developing independent research projects addressing unmet challenges in decompensated cirrhosis. Current activities focus on advancing research into major complications of cirrhosis, including bacterial infections, portal hypertension, hepatic encephalopathy, and acute kidney injury. hepatology.
Read more on our website
Strengthening global collaboration and scientific leadership
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Supporting collaborative liver disease research in Latin America
Through scientific coordination, methodological support, and collaboration with regional leaders, we will continue contributing to a globally connected and collaborative research environment in Latin America.
The launch of the LATAM-CLIF Consortium marked an important step toward strengthening collaborative research on chronic liver disease across Latin America. Established during the XXIX Brazilian Congress of Hepatology and affiliated with the Asociación Latinoamericana para el Estudio del Hígado (ALEH), the initiative brings together leading clinicians and researchers to promote multicenter studies, knowledge exchange, and regional capacity building in decompensated cirrhosis and acute-on-chronic liver failure (ACLF). The consortium builds on the foundations established through the ACLARA study and aims to harmonize research efforts across the region while fostering integration with international scientific networks.
Read more on our website
Consolidating our long-term vision for research excellence
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EF CLIF moves to an iconic location in Barcelona
This year marked several important milestones in our long-term strategy to strengthen research excellence, institutional leadership, and translational impact. From relocating to a new headquarters in Barcelona that reflects the our evolving identity and ambitions, to celebrating a decade of progress through the Grifols Chair and public–private collaboration initiatives, these developments highlights our commitment to building a sustainable and globally connected research environment. The establishment of the Strategic Advisory Board further reinforces this vision, providing renewed strategic guidance to support the next phase of scientific growth and innovation.
EF CLIF’s new headquarters at Torre Barcelona, located on Avinguda Diagonal next to Plaça Francesc Macià, marks an important step in the our continued growth and long-term vision. Within one of Barcelona’s most dynamic professional and innovation hubs and in close proximity to Campus Clínic, Hospital Clínic de Barcelona, and IDIBAPS, the new location strengthens opportunities for collaboration, supports the integration of research and clinical practice, and provides an ideal environment to expand our presence in chronic liver disease research at both local and international levels.
Read more on our website
Consolidating our long-term vision for research excellence
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A decade advancing translational liver research through public–private collaboration
The renewal of the framework agreement between EF CLIF, Hospital Clínic de Barcelona, and FRCB-IDIBAPS reinforces a decade-long commitment to advancing translational research in decompensated cirrhosis and acute-on-chronic liver failure (ACLF). Supporting the activities of the Grifols Chair Program, this collaboration has enabled major scientific advances in immune dysfunction and ACLF pathophysiology, while fostering a strong research environment through sustained public-private partnership.
Read more on our website
Consolidating our long-term vision for research excellence
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Over the past ten years, the initiative has supported five research projects with more than €1.25 million in funding, contributing to 30 scientific publications and eight doctoral theses, and strengthening international collaboration through the ENTR-CLIF network.
Bridging science and patient care
The first Grifols Chair Symposium, “Translating Science into the Clinic”, brought together leading experts from academia, hospitals, and industry to explore recent advances in translational research for chronic liver disease and related inflammatory conditions. Hosted by EF CLIF and IDIBAPS, the event highlighted how integrating cutting-edge omics technologies with clinical data can drive more effective and personalized patient care.
Consolidating our long-term vision for research excellence
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Internationally renowned speakers shared the latest insights into immune dysfunction and inflammation resolution, emerging applications of single-cell and spatial omics, and innovative therapeutic approaches, including developments in plasma-derived therapies. The symposium highlighted the importance of cross-sector collaboration and marked the 10-year anniversary of the shared commitment between EF CLIF, Hospital Clínic de Barcelona, and IDIBAPS to advancing translational research.
Read more on our website
Consolidating our long-term vision for research excellence
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New appointment to the Governing Board
Prof. Alberto Farias, Clinical Director of the Liver Transplantation Program at the University of São Paulo School of Medicine, was appointed member of the Governing Board in recognition of his leadership and longstanding contributions to chronic liver disease research. His appointment further strengthens the Governing Board’s international expertise in cirrhosis, liver transplantation, and acute-on-chronic liver failure (ACLF), while reinforcing our commitment to global scientific collaboration and strategic leadership in hepatology.
Consolidating our long-term vision for research excellence
Annual Report | 29
Establishment of the Strategic Advisory Board
Members of the Strategic Advisory Board
Jonel Trebicka
EF CLIF, Spain
Salvatore Piano University of Padova, Italy Salvador Augustin Boehringer Ingelheim
Julia Doerner
Boehringer Ingelheim
Tom H. Karlsen
University of Oslo
Percy Knolle
Technische Universität München
Pejvack Motlagh GENFIT Valerie Paradis AP–HP
Sakina Sayah-Jeanne
GENFIT
Joerg Schuettrumpf
Grifols
Debbie Shawcross
EASL
In 2025, the Strategic Advisory Board was constituted as a consultative body to provide independent guidance on our long-term vision, strategic priorities, and institutional development. Its main mission is to advise the Governing Board on key opportunities and challenges related to research innovation, partnerships, global positioning, and sustainable growth, supporting EF CLIF in advancing its mission and future impact.
Chair
Secretary
Appointed member
Research outputs
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Supporting independent investigator-led research and innovation
These contributions reflect our role as a catalyst for innovation, providing high-quality resources that allow researchers at all career stages to explore new hypotheses, validate findings, and develop translational insights. Indepent investigator-led ancillary studies approved by the Sample and Data Usage Committee in the year ended 31 December 2025 are: Evaluation of factors defining the natural history and response to therapy of patients hospitalized with an acute episode of hepatic encephalopathyPI: Maria Pilar Ballester, Hospital Clínico Universitario de Valencia, Spain
Validation the effectiveness of the COSSH-ACLFcriteria and prognostic score in non-Asian ACLF populations
PI: Jun Li, Zhejiang University School of Medicine, China Can replacing the whole blood cell count with neutrophil to limphocyte ration improve the predictive performance of the CLIF-C AD score?
PI: Maria Papp, University of Debrecen, Poland Subphenotypes of patients with cirrhosis and sepsis
PI: Marijke Peetermans, UZ Leuven, Belgium
In line with our commitment to advancing scientific knowledge and promoting collaboration, we actively support independent investigator-led research. This includes granting access to data and biospecimens from our flagship studies (namely, CANONIC, PREDICT, ACLARA, and CHANCE), enabling the development of ancillary projects that extend the impact of our research.
In 2025, this support facilitated eight new studies across Europe and Asia, focusing on the pathophysiology of chronic liver disease.
Research outputs
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Clonal hematoposieses as a predictor of the clinical course of patients with acutely decompensated cirrhosisPI: Emmanuel Weiss, Centre de recherche sur l'inflammation UMR 1149, France
HDL-based prognostic models for prediction of short-term survival in acutely decompensated cirrhosis
PI: Rudolf Stauber, Medical University of Graz, Austria
Task 6 in MICROB-PREDICT : Address geographic and gender differences, aging and effects of drugs in the progression of liver diseases
PI: Jonel Trebicka and Wenyi Gu, University Hospital Münster, Germany
Research outputs
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Scientific publications and communications
Open Access | Article Blood markers for type-1, -2, and -3 inflammation are associated with severity of acutely decompensated cirrhosis
J Hepatol 2025, 82(5):836–850
DOI: 10.1016/j.jhep.2024.10.028
Open Access | Article Gene score to quantify systemic inflammation in patients with acutely decompensated cirrhosis
Gut 2025, 74(8):1293–1307
DOI: 10.1136/gutjnl-2024-333876
Our scientific dissemination strategy spans peer-reviewed publications, conference proceedings, and presentations at leading international meetings. These outputs reflect our ongoing commitment to sharing results with the scientific community as soon as possible, promoting transparency, and fostering dialogue across disciplines.
Open Access | Article Low-dose hydrocortisone in cirrhotic patients with septic shock: A double-blind randomised placebo-controlled trial
Liver Int 2025, 45(9):e70257
DOI: 10.1111/liv.70257
Guidelines/Consensus Statements Defining organ failures in patients with cirrhosis: Consensus Statements
Gastroenterology 2025, 169(5):1043–1062
DOI: 10.1053/j.gastro.2025.05.026
Flagship research projects
Open Access | Article Performance of the China-CLIF framework in acute-on-chronic liver failure: A multicohort study across all aetiologies
Gut 2025, 75(1):131-146
DOI: 10.1136/gutjnl-2025-335651
Open Access | Review Acute-on-chronic liver failure (ACLF): The 'Kyoto Consensus'-steps from Asia
Hepatol Int 2025, 19(1):1–69
DOI: 10.1007/s12072-024-10773-4
Review Definition, diagnosis and epidemiology of acute-on-chronic liver failure
Liver Int 2025, 45(3):e15670
DOI: 10.1111/liv.15670
Research outputs
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Open Access | Article Macrophages downregulate NEDD9 to counteract S. typhimurium-mediated FAK-AKT activation and lysosome inhibition
Cell Death Dis 2025, 16(1):445
DOI: 10.1038/s41419-025-07634-9
EU-funded projects
Open Access | Editorial Validation of the CLIF-SIG score in patients with HBV-related acutely decompensated cirrhosis
Gut 2025, 74(11):1933–1935
DOI: 10.1136/gutjnl-2025-335810
Open Access | Article Fecal microbial load is a major determinant of gut microbiome variation and a confounder for disease associations
Cell 2025, 188(1):222–236
DOI: 10.1016/j.cell.2024.10.022
Ancillary studies
Open Access | Article Pediatric liver and kidney transplant recipients demonstrate greater serological response to SARS-CoV-2 vaccination than adults
Transplant Direct 2025, 11(5):e1787
DOI: 10.1097/TXD.0000000000001787
Open Access | Article Lactococcus A phages predict ACLF while Enterococcus B phages predict bacterial infection in decompensated cirrhosis
JHEP Rep 2025, 8(1):101622
DOI: 10.1016/j.jhepr.2025.101622
Open Access | Article Distinct immunometabolic signatures in circulating immune cells define disease outcome in acute-on-chronic liver failure
Hepatology 2025, 81(2):509–522
DOI: 10.1097/HEP.0000000000000907
Article Maladaptive emergency granulopoiesis predicts poor outcomes in patients hospitalized with decompensated cirrhosis
J Hepatol 2026, 84(4):749–765
DOI: 10.1016/j.jhep.2025.11.012
Open Access | Article Factors Associated with progression, resolution and mortality of patients with overt hepatic encephalopathy
J Clin Exp Hepatol 2026, 16(1):103410
DOI: 10.1016/j.jceh.2025.103410
Research outputs
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Open Access | Review Noninvasive assessment of hepatic decompensation
Hepatology 2025, 81(3):1019–1037
DOI: 10.1097/HEP.0000000000000618
Open Access | Article The postbiotic ReFerm® versus standard nutritional support in advanced alcohol-related liver disease (GALA-POSTBIO): A randomized controlled phase 2 trial
Nat Commun 2025, 16(1):5969
DOI: 10.1038/s41467-025-60755-9
Open Access | Article Serum villin-1-A novel marker of gut barrier damage in acutely decompensated cirrhosis: A cohort study and validation
Aliment Pharmacol Ther 2026, 63(7):1018–1032
DOI: 10.1111/apt.70481
Open Access | Article State of the art and the future of microbiome-based biomarkers: A multidisciplinary Delphi consensus
Lancet Microbe 2025, 6(2):100948
DOI: 10.1016/j.lanmic.2024.07.011
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ANNUAL REPORT 2025
Contents
Strengthening global collaboration and scientific leadership
Why the study of chronic liver disease matters
......................
...............................................................................................
19
Our foundations and purpose
........................................................
Building global consensus in cirrhosis and organ failure
19
..........
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We are shaping the future of chronic liver disease
Toward data-driven evidence in liver transplantation for ACLF
20
.....................................................................................................
The path forward
.............................................................................
Fostering international collaboration and scientific exchange
Our network
.........................................................................................
21
.............................................................................................
Our research environment
..............................................................
Consolidating our long-term vision for research excellence
Our progress
.........................................................................................
23
..................................................................................................
Statement from our Director
.........................................................
23
.....................
EF CLIF moves to an iconic location in Barcelona
Our year in numbers
......................................................................
11
A decade advancing translational liver research through public–private collaboration
Advancing translational research in advanced chronic liver disease
..........................................................
24
..........................................................................................
12
..............................
New appointments to the Governing Board
28
Risk stratification in decompensated cirrhosis
.........................
12
Establishment of the Strategic Advisory Board
.........................
29
A new experimental model to advance ACLF research
15
..........
Research outputs
...................................................................................
30
Advancing clinical research in critical care for advanced liver disease
Supporting independent investigator-led research and innovation
.....................................................................
16
30
..........................................................................................
Access to intensive care and treatment response in advanced liver disease
.............................
Scientific publications and communications
..................................................................
32
16
Why the study of chronic liver disease matters
Annual Report | 3
2,
Importantly, precipitating events associated with short term mortality among patients withACLF are not reflected in the conventional prognostic models for organ allocation falling short in prioritizing most severe patients with decompensated cirrhosis for liver transplantation. The alarming increase in obesity rates, harmful use of alcohol, and an aging population mean that liver disease will become an even greater global health concern over the next decade. Experts agree that the major causes of liver disease (i.e., alcohol-related liver disease, metabolic dysfunction-associated steatotic liver disease, and viral hepatitis) are amenable to prevention and treatment providing an opportunity to reduce the burden of liver disease and save lives. There is an urgent need to engage with policymakers and health authorities to invest in preventive actions and surveillance as regards chronic liver disease.
Because cirrhosis is a progressive disease, efficient treatment and management of patients with chronic liver disease are essential to improve patients’ survival rates and reduce the socioeconomic impact of the disease. It is remarkable to note that there have been no new, disease-modifying approaches to the treatment of chronic liver disease. Liver transplantation is the one treatment that has shown promise in improving patient survival by restoring essential functions where no alternative treatment of comparable effectiveness exists even for patients with severe acute-on-chronic liver failure (ACLF). A system for organ allocation that ensures equitable distribution continues to be an unmet medical need for patients with cirrhosis, and particularly those who progress into ACLF.
deaths worlwide due to liver disease
Cirrhosis is
Alcohol
15th
11th
leading cause of cirrhosis globally
leading cause of DALY
leading cause of deaths worldwide
HBV & HCV infections
Leading causes of
CIRRHOSIS
Overweight and obesity
Harmful use of alcohol
Our foundations and purpose
Annual Report | 4
To achieve this, we: Provide financial support for chronic liver disease research projects.Encourage participation in competitive research and innovation initiatives focused on translational advancements to improve clinical practice and early diagnosis.Develop and promote programs and activities to train healthcare professionals and researchers.Foster the dissemination of new knowledge about chronic liver disease. Guided by our mission and reflected in our current strategy, we advance knowledge and facilitate the translation of research into clinical practice, striving to improve care and enhance the quality of life for patients with chronic liver disease.
By funding and supporting cutting-edge research, we contribute to advance the understanding of chronic liver disease, develop lifesaving treatments, and improve patient care.
Our work goes beyond research—we engage with healthcare professionals, policymakers, scientists, and patients to drive innovation, inform clinical practice, and advocate for equitable access to care. Together, we aim to transform how chronic liver disease is managed, making a lasting impact for individuals, families, and communities worldwide. Our bylaws, as of 2015, state that our purpose is “to design, support, promote, and lead biomedical research studies and projects at a supranational level in the field of Health Sciences, particularly in the area of chronic liver failure”.
Annual Report | 5
We are shaping the future of chronic liver disease
The path forward
The journey into our vision will be guided by: Supporting collaborative projects, providing resources for high-impact research, and cultivating a culture of shared expertise and mentorship within the chronic liver disease research community. Conducting large-scale multicenter studies, partnering with international stakeholders, engaging liver patient communities, and advising policymakers on evidence-based standards and protocols.
We envision a thriving network of researchers and healthcare professionals across Europe, united in their pursuit of advancing knowledge on cirrhosis and its complications.
Our vision is to establish a global standard of care for decompensated cirrhosis and acute-on-chronic liver failure, informed by cutting-edge research and multidisciplinary collaboration.
We aspire to be a reference in driving innovation for the diagnosis, prognosis, and treatment of cirrhosis and acute-on-chronic liver failure. Our vision is a future where advanced tools and novel therapies significantly improve patient outcomes and quality of life.
Fostering cross-disciplinary collaboration, facilitating global knowledge exchange, and investing in the development and evaluation of innovative therapeutic and diagnostic solutions.
Our network
Annual Report | 6
Our global network of tertiary care hospitals, universities, and research centers brings together over 1,000 laboratory-based researchers, consultant physicians, intensivists, surgeons, nurses, and pathologists to carry out groundbreaking chronic liver disease research, ranging from translational studies to large-scale clinical trials.
Global projects
EASL-CLIF Consortium
ENTR-CLIF
96 centers in 22 countries
120 centers in 29 countries
23 centers in 7 countries
The Global Projects chapter offers the framework to promote research in cirrhosis around the world and brings the opportunity to strengthen connections between healthcare professionals across geographical borders.
The Grifols Chair promotes translational studies in centers across Europe and North America within the framework of the European Network for Translational Research- Chronic liver failure (ENTR-CLIF). Leading researchers and highly qualified scientists at these centers help moving scientific discovery from the laboratory to patients faster.
Through the large-scale observational studies we fund, these centers contribute to help drafting clinical practice guidelines that improve healhtcare and patients' outcomes. The European Association for the Study of the Liver (EASL)-Chronic Liver Failure (CLIF) Consortium also provides the framework to initiate new research ideas and programs, and offers the next generation of scientists and research leaders unique opportunities to drive future research and innovation in the area of liver disease.
Our research environment
Annual Report | 7
Find out more about the EF CLIF database
Our progress
Annual Report | 8
Statement from our Director
The strong performance of the score likely reflected its ability to capture the presence and intensity of systemic inflammation. This publication also initiated collaborative discussions involving Jonel Trebicka, Joan Clària, Ferran Aguilar, and myself on simplifying the score to facilitate bedside implementation. The second original study analyzed whole-blood RNA-seq data obtained at hospital admission from 1260 patients with ADC. Supported by the EU-funded DECISION project, this work was the first to identify maladaptive emergency granulopoiesis as a distinctive endotype associated with both pre-ACLF and poor survival outcomes. These findings provided the basis for a collaborative project with GENFIT aimed at generating a whole-blood single-cell multiomic atlas, including single-cell profiling of circulating hematopoietic stem and progenitor cells in patients with ADC.
In 2025, we continued advancing one of our two primary missions: addressing critical gaps in knowledge regarding the mechanisms underlying the most severe forms of acutely decompensated cirrhosis (ADC), with the aim of identifying clinically actionable biomarkers and novel therapeutic targets. In this context, our researchers and staff scientists published two original translational studies made possible through the prospective collection of blood samples within the seminal EF CLIF-sponsored PREDICT and ACLARA studies in patients with ADC. The first study described a 28-gene signature (the CLIF-SIG score) capable of accurately distinguishing, among 700 patients with ADC, those with pre-acute-on-chronic liver failure (pre-ACLF) or ACLF from those without these conditions.
This year’s report highlights our continued progress in translational and clinical research, with new initiatives advancing our understanding of chronic liver disease.
Our progress
Annual Report | 9
Joan Clària, Cristina Sánchez-Garrido, and Ferran Aguilar should be commended for their active contributions to these discussions. In 2025, we also continued advancing our second primary mission: conducting clinical research. Three developments deserve particular mention. First, Paolo Angeli, on behalf of the European Association for the Study of the Liver (EASL)-CLIF Consortium, continued collaborating with representatives of the EASL-Baveno Consortium on the design of a large European prospective observational study aimed at characterizing the trajectory of patients with compensated cirrhosis and the different patterns of decompensation episodes. During the year, the study protocol and electronic case report form were finalized, responsibilities among stakeholders clarified, and efforts concentrated on securing financial support. Second, our collaboration with GENFIT expanded through a Steering Committee
In parallel, Joan Clària completed preclinical studies evaluating the efficacy of novel therapeutic approaches developed by GENFIT in experimental models of ACLF. In 2025, we also welcomed Zhujun Cao, MD, PhD, from Shanghai Jiao Tong University School of Medicine as a Visiting Scientist. His one-year stay represents the first step in a broader collaboration between EF CLIF and Ruijin Hospital focused on clinical and translational research in ADC, particularly on blood transcriptomic alterations associated with immune cell production across disease severity stages. Discussions were also pursued with representatives of Boehringer Ingelheim to develop a translational research program in ADC focused on identifying novel biomarkers and clinically relevant patient endotypes. In this regard, Anna Bosch,
involving Jonel Trebicka, Javier Fernández, Paolo Angeli, and other members of our team. Together with GENFIT staff, the committee analyzed data from a large Komodo database to characterize the landscape of clinical phenotypes and clinical practice patterns in ADC across the United States. This collaboration resulted in abstracts accepted for oral and poster presentation at American Association for the Study of Liver Diseases (AASLD)’s The Liver Meeting®, representing the first step toward a series of collaborative scientific publications. Third, discussions involving GENFIT representatives, the U.S. Food and Drug Administration, Jonel Trebicka, Paolo Angeli, and myself led us to reconsider the conceptual framework traditionally used to design clinical trials in patients with severe ADC. While short-term mortality remains a critical endpoint, additional outcomes such as hospital discharge, days free from organ support, and incidence of nosocomial infections are increasingly recognized as
Our progress
Annual Report | 10
including active participation from EF CLIF investigators. In addition, Jonel Trebicka and I, together with investigators from the EASL-Baveno Consortium, co-authored a review article on the interaction between inflammation and portal hypertension in cirrhosis progression. This publication exemplifies the collaborative effort to overcome traditional conceptual silos separating inflammation and portal hypertension in the understanding of cirrhosis progression. Nearly ten years ago, EF CLIF initiated the process that ultimately led to the ACLARA study across Latin America. Beyond its resulting scientific publication in 2023, this initiative continued generating important benefits in 2025. A major milestone was the appointment of Alberto Farias to the EF CLIF Governing Board, reflecting our commitment to sustaining a strong two-way collaboration with Latin American colleagues. This close relationship was further demonstrated by
clinically relevant. Addressing these questions became a strategic priority for us in 2025, with contributions from our research team and the Data Management Center led by Cristina Sánchez-Garrido and Eva Usón. During 2025, we have also contributed to the ongoing global harmonization of diagnostic criteria for organ failures and ACLF through three additional publications. One original article, developed in collaboration with colleagues from the Chinese Group on the Study of Severe Hepatitis B (COSSH) Consortium, evaluated the broader applicability of the China-CLIF framework across diverse etiologies and varying severities of ACLF using EF CLIF patient cohorts. Two further position papers, published under the auspices of the Asian Pacific Association for the Study of the Liver (APASL) and AASLD, further illustrated the international commitment to harmonization efforts,
the participation of Paolo Angeli, Chair of the EASL-CLIF Consortium, and myself in the official launch of the LATAM-CLIF Consortium on 14 October in Rio de Janeiro, Brazil. Additional evidence of this growing collaboration can be seen in recent EF CLIF publications that increasingly integrate Latin American and European authorship. Furthermore, Latin American researchers ranked among the top contributors to patient recruitment in the CHANCE study, whose first rounds of analyses were conducted by our Data Management Center team at the end of 2025.
Prof. Richard MoreauDirector of EF CLIF
Our progress
Annual Report | 11
Our year in numbers
Currently, we fund
We published
We enabled
We participated in
19 papers
n new ancillary studies
1 large-scale observational study
5 scientific events
16 of these in open access journals
by independent researchers
We made
We raised over
We received
We welcomed
204 followers
€1.5 M
€624,00
media appearances - that we know of
across social media channels
from donations
in EU funding
Click on interactive elements to read more.
Advancing translational research in advanced chronic liver disease
Annual Report | 12
Risk stratification in decompensated cirrhosis
Predicting which patients with decompensated cirrhosis will rapidly deteriorate remains one of the major challenges in hepatology, as conventional biomarkers often fail to accurately capture the severity of systemic inflammation and immune dysfunction driving disease progression. During the year, we have carried out complementary studies exploring transcriptomic and immune-based approaches to risk stratification. One study introduced the CLIF-SIG score, a gene expression-based tool capable of improving prediction of acute-on-chronic liver failure (ACLF) and severe outcomes beyond traditional inflammatory markers.
In parallel, another investigation identified maladaptive activation of emergency granulopoiesis and the expansion of immature neutrophils as key immune mechanisms associated with poor prognosis in decompensated cirrhosis. Together, these findings contribute to a more precise understanding of systemic inflammation in advanced chronic liver disease and support the development of personalized strategies for early diagnosis, prognostic assessment, and therapeutic intervention.
Advancing translational research in advanced chronic liver disease
Annual Report | 13
Linking neutrophil production to outcomes in decompensated cirrhosis
A large transcriptomic analysis identified a stress-induced blood immune signature associated with poor outcomes in patients with decompensated cirrhosis. The study showed that maladaptive activation of emergency granulopoiesis—driven by the IL-6–STAT3–C/EBPB axis and leading to increased production of immature and immunosuppressive neutrophils—characterises patients who develop acute-on-chronic liver failure (ACLF) within 28 days or die without liver transplantation within 90 days of hospital admission. These findings highlight a key immune mechanism underlying disease progression and point to new opportunities for early risk stratification and therapeutic intervention.
This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement no. 847949.
Read more on our website
Advancing translational research in advanced chronic liver disease
Annual Report | 14
A gene-based score to improve risk prediction in acutely decompensated cirrhosis
with most patients who progressed to ACLF already identified at admission. These findings highlight the potential of transcriptomic profiling to refine risk stratification, support clinical decision-making, and enable more precise patient selection and monitoring in future therapeutic trials.
A newly developed gene-based score provided a more accurate assessment of systemic inflammation in patients with acutely decompensated cirrhosis, enabling improved prediction of disease progression and severe complications. Based on the identification of immune cell-related gene expression patterns, the CLIF-SIG score outperformed conventional biomarkers such as white cell count and C-reactive protein in identifying patients at high risk, including those who develop acute-on-chronic liver failure. In a cohort of 700 hospitalized patients, the score demonstrated strong predictive performance across different etiologies, clinical triggers, and patient populations,
Read more on our website
Advancing translational research in advanced chronic liver disease
Annual Report | 15
A new experimental model to advance ACLF research
This refined preclinical model addresses a major gap in ACLF research and provides a valuable platform to investigate disease mechanisms and evaluate future therapeutic strategies.
New mouse model was developed and validated that successfully reproduces the systemic inflammation and multiorgan failure characteristic of acute-on-chronic liver failure (ACLF). By combining chemically induced cirrhosis with polymicrobial peritonitis, the model closely reflects the clinical features and heterogeneity observed in patients, including liver, kidney, brain, circulatory, respiratory, and coagulation dysfunction. Importantly, the study adapts EASL-CLIF-C clinical definitions for use in mice, enabling closer comparability between experimental findings and the human condition.
Read more on our website
Advancing clinical research in critical care for advanced liver disease
Annual Report | 16
challenging traditional assumptions regarding intensive care unit admission in patients with advanced liver cancer. Together, these findings support a more individualized and evidence-based approach to critical care, with the ultimate goal of improving survival and treatment opportunities in advanced liver disease.
Access to intensive care and treatment response in advanced liver disease
Managing critically ill patients with advanced liver disease remains one of the greatest challenges in hepatology, requiring timely therapeutic decisions and equitable access to intensive care. We contributed important evidence to guide critical care management in high-risk patient populations, including patients with cirrhosis, septic shock, and advanced hepatocellular carcinoma receiving immunotherapy. Through large international clinical studies, these efforts helped clarify the role and limitations of specific therapeutic interventions, such as hydrocortisone in septic shock, while also
Advancing clinical research in critical care for advanced liver disease
Annual Report | 17
Reassessing intensive care access in advanced liver cancer
A large international study challenged long-standing barriers to intensive care unit (ICU) admission for patients with advanced hepatocellular carcinoma (HCC) receiving immunotherapy. Traditionally considered poor candidates for critical care, many of these patients were shown to survive severe complications and successfully resume cancer treatment following ICU admission. The study showed encouraging short- and mid-term survival rates among patients admitted for severe immune-related adverse events or complications such as variceal bleeding. The findings highlight the evolving role of critical care in the era of immunotherapy and support a more individualized approach to ICU admission in patients with advanced liver cancer.
Read more on our website
Advancing clinical research in critical care for advanced liver disease
Annual Report | 18
New evidence on steroid therapy in cirrhosis and septic shock
These results provide important evidence to guide critical care management and refine therapeutic strategies in this high-risk patient population.
The SCOTCH trial, the largest randomized study conducted to date in patients with cirrhosis and septic shock, evaluated the efficacy of low-dose hydrocortisone in critically ill patients admitted to intensive care units. The study showed that hydrocortisone did not improve short-term survival or overall shock resolution in patients requiring low to moderate vasopressor support, while some adverse metabolic effects were more frequent in treated patients. Importantly, the findings identified the severity of liver disease, the presence of acute-on-chronic liver failure (ACLF), and timely administration of appropriate antibiotics as the main predictors of survival.
Read more on our website
Strengthening global collaboration and scientific leadership
Annual Report | 19
Building global consensus in cirrhosis and organ failure
practice more closely with intensive care standards. By establishing shared diagnostic thresholds and unified clinical definitions, this work represents an important step toward harmonizing ACLF research and clinical management worldwide.
We took part in an international panel of hepatologists and intensivists, contributing to the development of new consensus statements that establish standardized definitions for organ system failures and acute-on-chronic liver failure (ACLF) in patients with cirrhosis. This initiative addresses longstanding variability in diagnostic criteria across institutions and research groups, providing a common framework to improve patient care, enable comparison of clinical outcomes, and strengthen the design of future clinical research. The consensus defines failure across major organ systems and highlights infection and immune dysfunction as central drivers of ACLF, while aligning hepatology
Read more on our website
Strengthening global collaboration and scientific leadership
Annual Report | 20
Toward data-driven evidence in liver transplantation for ACLF
As final analyses progress, the CHANCE study is expected to provide important prospective evidence to guide liver transplantation strategies, improve risk stratification, and support fairer access to transplantation for patients with ACLF.
We hosted a strategic working meeting with the leadership and coordination teams of the CHANCE study to advance analyses supporting the study’s first core publication. Discussions focused on key clinical endpoints, including 1-year graft and patient survival following liver transplantation in patients with ACLF grade 2 or 3, compared with patients with decompensated cirrhosis without ACLF, as well as transplant-free survival in patients with ACLF who were not listed for liver transplantation. Additional analyses addressed post-transplant mortality, waiting-list outcomes, and the development of new prognostic and futility models to support clinical decision-making in critically ill patients.
Read more on our website
Strengthening global collaboration and scientific leadership
Annual Report | 21
Fostering international collaboration and scientific exchange
Hosting international talent to advance ACLF research
We welcomed Dr. Zhujun Cao from Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, China, for a one-year research stay in Barcelona. Working under the supervision of Prof. Richard Moreau, Dr. Cao is investigating the immunopathogenesis of acute-on-chronic liver failure (ACLF) using prospective cohorts and multi-omics approaches. His stay reflects the growing scientific collaboration between EF CLIF and Chinese research groups and highlights our commitment to fostering international scientific exchange, mentorship, and collaborative research in chronic liver disease.
Strengthening international collaboration and scientific exchange remained a central component of our mission throughout the year. Through initiatives such as the Visiting Scientist Program and support for emerging regional research networks, we continue fostering knowledge sharing, mentorship, and long-term scientific partnerships across the global chronic liver disease community. Together, these initiatives contribute to building a more connected, collaborative research environment in hepatology.
Read more on our website
Strengthening global collaboration and scientific leadership
Annual Report | 22
Supporting the next generation of chronic liver disease leaders
Through regular scientific discussions and guidance from senior investigators, the initiative aims to empower emerging leaders and stimulate innovative, clinically relevant research in hepatology.
The Inspiring and Writing Group welcomed eight new junior researchers, reinforcing our commitment to fostering collaboration, mentorship, and innovation in chronic liver disease research. Building on our landmark datasets and biobank, the group continues to provide a collaborative platform for developing independent research projects addressing unmet challenges in decompensated cirrhosis. Current activities focus on advancing research into major complications of cirrhosis, including bacterial infections, portal hypertension, hepatic encephalopathy, and acute kidney injury. hepatology.
Read more on our website
Strengthening global collaboration and scientific leadership
Annual Report | 23
Supporting collaborative liver disease research in Latin America
Through scientific coordination, methodological support, and collaboration with regional leaders, we will continue contributing to a globally connected and collaborative research environment in Latin America.
The launch of the LATAM-CLIF Consortium marked an important step toward strengthening collaborative research on chronic liver disease across Latin America. Established during the XXIX Brazilian Congress of Hepatology and affiliated with the Asociación Latinoamericana para el Estudio del Hígado (ALEH), the initiative brings together leading clinicians and researchers to promote multicenter studies, knowledge exchange, and regional capacity building in decompensated cirrhosis and acute-on-chronic liver failure (ACLF). The consortium builds on the foundations established through the ACLARA study and aims to harmonize research efforts across the region while fostering integration with international scientific networks.
Read more on our website
Consolidating our long-term vision for research excellence
Annual Report | 24
EF CLIF moves to an iconic location in Barcelona
This year marked several important milestones in our long-term strategy to strengthen research excellence, institutional leadership, and translational impact. From relocating to a new headquarters in Barcelona that reflects the our evolving identity and ambitions, to celebrating a decade of progress through the Grifols Chair and public–private collaboration initiatives, these developments highlights our commitment to building a sustainable and globally connected research environment. The establishment of the Strategic Advisory Board further reinforces this vision, providing renewed strategic guidance to support the next phase of scientific growth and innovation.
EF CLIF’s new headquarters at Torre Barcelona, located on Avinguda Diagonal next to Plaça Francesc Macià, marks an important step in the our continued growth and long-term vision. Within one of Barcelona’s most dynamic professional and innovation hubs and in close proximity to Campus Clínic, Hospital Clínic de Barcelona, and IDIBAPS, the new location strengthens opportunities for collaboration, supports the integration of research and clinical practice, and provides an ideal environment to expand our presence in chronic liver disease research at both local and international levels.
Read more on our website
Consolidating our long-term vision for research excellence
Annual Report | 25
A decade advancing translational liver research through public–private collaboration
The renewal of the framework agreement between EF CLIF, Hospital Clínic de Barcelona, and FRCB-IDIBAPS reinforces a decade-long commitment to advancing translational research in decompensated cirrhosis and acute-on-chronic liver failure (ACLF). Supporting the activities of the Grifols Chair Program, this collaboration has enabled major scientific advances in immune dysfunction and ACLF pathophysiology, while fostering a strong research environment through sustained public-private partnership.
Read more on our website
Consolidating our long-term vision for research excellence
Annual Report | 26
Over the past ten years, the initiative has supported five research projects with more than €1.25 million in funding, contributing to 30 scientific publications and eight doctoral theses, and strengthening international collaboration through the ENTR-CLIF network.
Bridging science and patient care
The first Grifols Chair Symposium, “Translating Science into the Clinic”, brought together leading experts from academia, hospitals, and industry to explore recent advances in translational research for chronic liver disease and related inflammatory conditions. Hosted by EF CLIF and IDIBAPS, the event highlighted how integrating cutting-edge omics technologies with clinical data can drive more effective and personalized patient care.
Consolidating our long-term vision for research excellence
Annual Report | 27
Internationally renowned speakers shared the latest insights into immune dysfunction and inflammation resolution, emerging applications of single-cell and spatial omics, and innovative therapeutic approaches, including developments in plasma-derived therapies. The symposium highlighted the importance of cross-sector collaboration and marked the 10-year anniversary of the shared commitment between EF CLIF, Hospital Clínic de Barcelona, and IDIBAPS to advancing translational research.
Read more on our website
Consolidating our long-term vision for research excellence
Annual Report | 28
New appointment to the Governing Board
Prof. Alberto Farias, Clinical Director of the Liver Transplantation Program at the University of São Paulo School of Medicine, was appointed member of the Governing Board in recognition of his leadership and longstanding contributions to chronic liver disease research. His appointment further strengthens the Governing Board’s international expertise in cirrhosis, liver transplantation, and acute-on-chronic liver failure (ACLF), while reinforcing our commitment to global scientific collaboration and strategic leadership in hepatology.
Consolidating our long-term vision for research excellence
Annual Report | 29
Establishment of the Strategic Advisory Board
Members of the Strategic Advisory Board
Jonel Trebicka EF CLIF, Spain Salvatore Piano University of Padova, Italy Salvador Augustin Boehringer Ingelheim Julia Doerner Boehringer Ingelheim Tom H. Karlsen University of Oslo Percy Knolle Technische Universität München
Pejvack Motlagh GENFIT Valerie Paradis AP–HP Sakina Sayah-Jeanne GENFIT Joerg Schuettrumpf Grifols Debbie Shawcross EASL
In 2025, the Strategic Advisory Board was constituted as a consultative body to provide independent guidance on our long-term vision, strategic priorities, and institutional development. Its main mission is to advise the Governing Board on key opportunities and challenges related to research innovation, partnerships, global positioning, and sustainable growth, supporting EF CLIF in advancing its mission and future impact.
Chair
Secretary
Appointed member
Research outputs
Annual Report | 30
Supporting independent investigator-led research and innovation
These contributions reflect our role as a catalyst for innovation, providing high-quality resources that allow researchers at all career stages to explore new hypotheses, validate findings, and develop translational insights. Indepent investigator-led ancillary studies approved by the Sample and Data Usage Committee in the year ended 31 December 2025 are: Evaluation of factors defining the natural history and response to therapy of patients hospitalized with an acute episode of hepatic encephalopathyPI: Maria Pilar Ballester, Hospital Clínico Universitario de Valencia, Spain
Validation the effectiveness of the COSSH-ACLFcriteria and prognostic score in non-Asian ACLF populations PI: Jun Li, Zhejiang University School of Medicine, China Can replacing the whole blood cell count with neutrophil to limphocyte ration improve the predictive performance of the CLIF-C AD score? PI: Maria Papp, University of Debrecen, Poland Subphenotypes of patients with cirrhosis and sepsis PI: Marijke Peetermans, UZ Leuven, Belgium
In line with our commitment to advancing scientific knowledge and promoting collaboration, we actively support independent investigator-led research. This includes granting access to data and biospecimens from our flagship studies (namely, CANONIC, PREDICT, ACLARA, and CHANCE), enabling the development of ancillary projects that extend the impact of our research. In 2025, this support facilitated eight new studies across Europe and Asia, focusing on the pathophysiology of chronic liver disease.
Research outputs
Annual Report | 31
Clonal hematoposieses as a predictor of the clinical course of patients with acutely decompensated cirrhosisPI: Emmanuel Weiss, Centre de recherche sur l'inflammation UMR 1149, France
HDL-based prognostic models for prediction of short-term survival in acutely decompensated cirrhosis PI: Rudolf Stauber, Medical University of Graz, Austria Task 6 in MICROB-PREDICT : Address geographic and gender differences, aging and effects of drugs in the progression of liver diseases PI: Jonel Trebicka and Wenyi Gu, University Hospital Münster, Germany
Research outputs
Annual Report | 32
Scientific publications and communications
Open Access | Article Blood markers for type-1, -2, and -3 inflammation are associated with severity of acutely decompensated cirrhosis J Hepatol 2025, 82(5):836–850 DOI: 10.1016/j.jhep.2024.10.028
Open Access | Article Gene score to quantify systemic inflammation in patients with acutely decompensated cirrhosis Gut 2025, 74(8):1293–1307 DOI: 10.1136/gutjnl-2024-333876
Our scientific dissemination strategy spans peer-reviewed publications, conference proceedings, and presentations at leading international meetings. These outputs reflect our ongoing commitment to sharing results with the scientific community as soon as possible, promoting transparency, and fostering dialogue across disciplines.
Open Access | Article Low-dose hydrocortisone in cirrhotic patients with septic shock: A double-blind randomised placebo-controlled trial Liver Int 2025, 45(9):e70257 DOI: 10.1111/liv.70257
Guidelines/Consensus Statements Defining organ failures in patients with cirrhosis: Consensus Statements Gastroenterology 2025, 169(5):1043–1062 DOI: 10.1053/j.gastro.2025.05.026
Flagship research projects
Open Access | Article Performance of the China-CLIF framework in acute-on-chronic liver failure: A multicohort study across all aetiologies Gut 2025, 75(1):131-146 DOI: 10.1136/gutjnl-2025-335651
Open Access | Review Acute-on-chronic liver failure (ACLF): The 'Kyoto Consensus'-steps from Asia Hepatol Int 2025, 19(1):1–69 DOI: 10.1007/s12072-024-10773-4
Review Definition, diagnosis and epidemiology of acute-on-chronic liver failure Liver Int 2025, 45(3):e15670 DOI: 10.1111/liv.15670
Research outputs
Annual Report | 33
Open Access | Article Macrophages downregulate NEDD9 to counteract S. typhimurium-mediated FAK-AKT activation and lysosome inhibition Cell Death Dis 2025, 16(1):445 DOI: 10.1038/s41419-025-07634-9
EU-funded projects
Open Access | Editorial Validation of the CLIF-SIG score in patients with HBV-related acutely decompensated cirrhosis Gut 2025, 74(11):1933–1935 DOI: 10.1136/gutjnl-2025-335810
Open Access | Article Fecal microbial load is a major determinant of gut microbiome variation and a confounder for disease associations Cell 2025, 188(1):222–236 DOI: 10.1016/j.cell.2024.10.022
Ancillary studies
Open Access | Article Pediatric liver and kidney transplant recipients demonstrate greater serological response to SARS-CoV-2 vaccination than adults Transplant Direct 2025, 11(5):e1787 DOI: 10.1097/TXD.0000000000001787
Open Access | Article Lactococcus A phages predict ACLF while Enterococcus B phages predict bacterial infection in decompensated cirrhosis JHEP Rep 2025, 8(1):101622 DOI: 10.1016/j.jhepr.2025.101622
Open Access | Article Distinct immunometabolic signatures in circulating immune cells define disease outcome in acute-on-chronic liver failure Hepatology 2025, 81(2):509–522 DOI: 10.1097/HEP.0000000000000907
Article Maladaptive emergency granulopoiesis predicts poor outcomes in patients hospitalized with decompensated cirrhosis J Hepatol 2026, 84(4):749–765 DOI: 10.1016/j.jhep.2025.11.012
Open Access | Article Factors Associated with progression, resolution and mortality of patients with overt hepatic encephalopathy J Clin Exp Hepatol 2026, 16(1):103410 DOI: 10.1016/j.jceh.2025.103410
Research outputs
Annual Report | 34
Open Access | Review Noninvasive assessment of hepatic decompensation Hepatology 2025, 81(3):1019–1037 DOI: 10.1097/HEP.0000000000000618
Open Access | Article The postbiotic ReFerm® versus standard nutritional support in advanced alcohol-related liver disease (GALA-POSTBIO): A randomized controlled phase 2 trial Nat Commun 2025, 16(1):5969 DOI: 10.1038/s41467-025-60755-9
Open Access | Article Serum villin-1-A novel marker of gut barrier damage in acutely decompensated cirrhosis: A cohort study and validation Aliment Pharmacol Ther 2026, 63(7):1018–1032 DOI: 10.1111/apt.70481
Open Access | Article State of the art and the future of microbiome-based biomarkers: A multidisciplinary Delphi consensus Lancet Microbe 2025, 6(2):100948 DOI: 10.1016/j.lanmic.2024.07.011
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