EFCLIF-AR-2023

A year of enlightment and consensus building

ANNUAL REPORT 2023

Why the study of chronic liver disease matters

Contents

Our network

Our progress in 2023

Taking bold steps towards a transformation of care

Liver transplantation in severe ACLF - A global challengeAI solutions for liver transplant organ allocation in Europe

Celebrating 10 years of the first evidence-based diagnostic criteria for ACLFContributing expert opinions on chronic liver disease

Supporting independent investigator-led research and innovation

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5

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11121314151617

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2223

1821

A spotlight on Latin AmericaContributing to EASL Clinical Practice Guidelines on ACLFMetabolomic models for ACLF predictionNew insights on the role of albumin in cirrhosisProtective effect of omega-3 lipid mediators in MAFLDA liver dialysis device for treatment of cirrhosis and ACLFGuiding effective COVID-19 vaccination strategies

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Connecting and engaging with the hepatology community

Removing barriers to access liver transplantation

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18

Scientific publications

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Why the study of chronic liver disease matters

Our purpose

Lead the way on early diagnosis and treatment to improve prognosis, survival and quality of life for patients with chronic liver disease.

EF CLIF has made pioneering efforts in conducting a series of large, international prospective studies that have been instrumental in reclassifying the trajectory of patients with chronic liver disease and led to the clinical, prognostic and pathophysiological definition of the syndrome referred to as “acute-on-chronic liver failure” characterized by acute decompensation of cirrhosis, severe systemic inflammation, organ failures, and high short-term mortality. We are promoting the adoption of best clinical practices in managing patients with chronic liver disease, thereby contributing to the creation of more sustainable and equitable healthcare systems.

The European Foundation for the Study of Chronic Liver Failure’s fundamental purpose, reflected in its founding Statements of 2015, is to advance knowledge and promote research and education in liver disease to improve the prognosis of patients living with chronic liver disease.

,

deaths worlwide due to liver disease

2,

11th

leading cause of deaths worldwide

15th

leading cause of DALY

Cirrhosis is

Overweight and obesity

HBV & HCV infections

Leading causes of

CIRRHOSIS

Harmful use of alcohol

Alcohol

leading cause of cirrhosis globally

!

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EF CLIF has three roles that are key to performing its purpose:

We engage with national and international liver patient communities and world-renown hepatology and liver transplant professional associations to raise awareness of the complications of cirrhosis and provide expert advice to develop guidelines on good clinical practice to ensure that treatment and care of patients with liver disease is accessible and harmonized in Europe and around the world.

At the crossroad between disciplines, we forge links with researchers and professionals across sectors to spark new ideas, advance knowledge, and redefine education. Through collaborative research, we translate these efforts into tangible improvements in care for patients with chronic liver disease.

Our ambition

European fellowship

As a fellowship of dedicated researchers and healthcare professionals across Europe, we recognize clinical research excellence and every year nominate new members of the EASL-CLIF Consortium to contribute to advancing knowledge on the pathophysiology, diagnostics, and treatment of cirrhosis through the collaborative research projects we sponsor.

International academy

Through our global network, we foster collaboration among international partners in carring out large-scale multicenter studies to further our understanding of liver function and disease, advise policymakers on new standards and protocols for the provision of equitable care, and ultimately improve survival and the quality of life of patients with cirrhosis.

Knowledge transfer and innovation

As a knowledge provider, we facilitate the exchange of ideas across disciplines and geographical borders. We enable open collaboration to address global unmet medical needs for patients with cirrhosis. We are inspired to develop advanced diagnostic, prognostic and predictive tools for acute-on-chronic liver failure progression in patients with cirrhosis. We promote and carry out clinical studies to evaluate the efficacy and safety of novel therapeutic approaches.

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Our network

EASL-CLIF Consortium

ENTR-CLIF

Global projects

120 centers in 29 countries

23 centers in 7 countries

96 centers in 22 countries

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.

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.

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.

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Our progress in 2023

2 large-scale observational studies

Currently, we fund

15 papers*

We published

11 in open access journals

20 scientific events

We participated in over

462 patients

We recruited

in CHANCE

6 new ancillary studies

We enabled

by independent researchers

€260,000

We raised over

in EU funding

12

We made

media appearances - that we know of

74%

We grew our social media community by

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* See complete list of publications in pp. 25–26

Statement from our former Director

Last year marked the 10th aniversary of the publication of the CANONIC study, a significant milestone that greatly advanced our understanding of cirrhosis.

A group of European investigators, noting the attention on hepatitis C and liver cancer compared to cirrhosis, initiated a call for broader research focus. They emphasized the need to explore not only traditional complications like ascites and variceal bleeding, but also new pathways like immune dysfunction and systemic inflammation, crucial for understanding multiorgan failure and mortality in cirrhosis.In 2004, the Asian-Pacific Association for the Study of the Liver (APASL) introduced a new syndrome in cirrhosis referred to as acute-on-chronic liver failure (ACLF). ACLF was originally defined by and acute onset of liver failure, typically triggered by factors like

alcohol toxicity or viral hepatitis, followed by jaundice and the rapid development of ascites and/or hepatic encephalopathy within a month. The initial defiition of ACLF excluded patients with prior decompensation or extrahepatic insults such as bacterial infections, with extrahepatic organ failures considered terminal events.Our Asian colleagues led the charge in redefining the pathophysiology of acute decompensation of cirrhosis. However, the APASL proposal presented two significant limitations. Firstly, ACLF was defined trhough expert consensus rather than empirical data, resembling the definition of acute liver failure (ALF) from the 1960s, which emphasized an acute liver insult followed by hepatic encephalopathy in patient without underlying liver disease. Secondly, the definition overlooked extrahepatic organ failures, commonly occuring together with liver failure and bacterial infections in patients hospitalized with acutely decompensated cirrhosis.

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Initially, the European investigators applied the APASL inclusion and exclusion criteria to the first 400 prospectively evaluated patients. However, this initial assessment revealed that the ACLF syndrome, as defined by the APASL, was rare and of limited relevance in European patients with acutely decompensated cirrhosis. Following this analysis, the CANONIC study proceeded with a refined objective: to characterize the ACLF syndrome using objective data and recognizing extrahepatic organ failures as an integral component of the syndrome.The EASL-CLIF-C criteria for ACLF, which relayed on the function of the six relevant organ systems included in the SOFA score (liver, kidneys, brain, coagulation, circulation, and respiration), gained swift acceptance in Europe, America, and Asia.Over 70% of studies conducted on patients with ACLF have utilized the EASL-CLIF-C criteria for diagnosing and assessing the severity of the syndrome.

So far, the APASL criteria has undergone two modifications, integrating some elements of the EASL-CLIF-C criteria. Comparative studies between the two criteria indicate that they identify different patient populations, with the EASL-CLIF-C criteria significantly outperforming the APASL criteria in identifying patients with poor short-term prognosis.The CANONIC study laid the groundwork for the establishment of the European Foundation for the Study of Chronic Liver Failure (EF CLIF), and inspired three additional large-scale prospective observational investigations (PREDICT, ACLARA, and CHANCE) including sequential biobanked samples for omics research, now used by independent investigators in diverse multicenter ancillary projects, some supported by the European Union.

The European investigators recoginized the potential of a new syndrome in the 21st century to catalyze research in cirrhosis. They took the first step by establishing a research platform aimed at identifying such a syndrome among hospitalized patients with acutely decompensated cirrhosis. This platorm, the European Association for the Study of the Liver-Chronic Liver Failure Consortium (EASL-CLIF-C), involved a consortium of university hospitals to carry out large-scale prospective observational studies, sponsors like Fundació Clínic per a la Recerca Biomèdica, Cellex Foundation and Grifols for financial and logistical support, and academic support from EASL. Launched in 2009, the CANONIC study involved 1343 patients with acutely decompensated cirrhosis requiring hospitalization for the management of an acute episode of ascites, hepatic encephalopathy, gastrointestinal hemorrhage, or a combination thereof.

Professor Vicente ArroyoPresident of the Board of Trustees

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Welcome from our new Director

During this period, EF CLIF has spearheaded research that has provided an evidence-based understanding of acutely decompensated cirrhosis, introducing a new nomenclature in medicine. The CANONIC study, promoted by EF CLIF, characterized a new clinical syndrome named acute-on-chronic liver failure (ACLF), showing that it is, in fact, a clinical entity distinct from “mere” acutely decompensated cirrhosis. Through the PREDICT and ACLARA studies, EF CLIF elucidated the upstream factors leading to non-elective hospital admissions among patients with cirrhosis, including common clinically apparent precipitants like infection and alcohol-related hepatis, as well as comorbidities such as heart failure, ethnicity and genetic ancestry, and disparities in healthcare access. Furthermore, the PREDICT study identified three distinct clinical trajectories among patients non-electively admitted to hospital for acutely decompensated cirrhosis without ACLF. EF CLIF’s significat achievement lies in demonstrating that

As the new Director of EF CLIF, I must recognize the remarkable decade-long journey of EF CLIF led by Vicente Arroyo.

ACLF is not only clinically distinct from mere acute decopmpensation of cirrhosis, but also exhibits unique cellular and molecular features associated to intense systemic inflammation. These insights were obtained from the analysis of white blood cell counts and the use of omics (metabolomics, lipidomics, cytokinomics, transcriptomics) in blood samples from large patient cohorts enrolled prospectively in studies carried out by EF CLIF. Notably, EF CLIF has conducted the first genome-wide association study using samples from these three seminal studies. In recent years, EF CLIF has initiated two groundbreaking studies primed to revolutionize the management of patients with cirrhosis and severe ACLF. The first study, led by Thierry Gustot and Rajiv Jalan, is the observational CHANCE study. It aims to prospectively investigate transplantation in a large cohort of patients with severe ACLF across different continents, including Europe, the Americas, and Asia. This study seeks to validate the efficacy of liver

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Furthermore, our translational research will tackle the critical question of gut microbiota alterations associated with intestinal barrier dysfunction, leading to abnormal microbial translocation. This endeavor aligns with the ongoing EU-funded project MICROB-PREDICT coordinated by Jonel Trebicka, and an ambitious research program devised by Joan Clària in collaboration with key stakeholders. Ultimately, our translational research activities aim to pinpoint cellular and molecular targets for novel therapeutic approaches, fostering fruitful collaborations with industrial partners such as GENFIT.

transplantation in critically ill patients, potentially refining criteria for organ allocation, including futility criteria. CHANCE is actively recruiting participants and will provide invaluable biological samples, including liver specimens, for translational research. The second study, led by Javier Fernández, is the interventional APACHE study, an open-label randomized trial assessing plasma exchange for patients with severe ACLF. Preliminary results from APACHE show promise regarding the use of plasma exchange in this indication.My vision for the upcoming years is deeply rooted in EF CLIF's past successes and aims to propel us forward with impactful clinical and translational studies. Leveraging the growing network of European liver units affiliated with the

EASL-CLIF Consortium, led by Paolo Angeli, EF CLIF will launch new clinical interventional studies. Additionally, under the lead of Thierry Gustot, the Inspiring Writing Group will drive clinical studies utilizing granular data collected from our three seminal studies, merged into a harmonized "meta-database" overseen by Javier Fernández and Cristina Sánchez-Garrido.Our chapter on translational research, led by Joan Clària, will continue characterizing cellular and molecular features of systemic inflammation in well-annotated patient subgroups. This effort will be supported by ongoing EU-funded projects like DECISION, coordinated by Pierre-Emmanuel Rautou. Specifically, we will seek to identify immune-cell subsets pivotal in multiorgan failure development and understand where these cells acquire their aggressive phenotype. Integration of omics data and white blood cell counts will elucidate changes in extracellular inflammatory signals and immune cell status.

Professor Richard MoreauDirector of EF CLIF

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Taking bold steps towards a transformation of care

A spotlight on Latin America

The ACLARA study, a large prospective observational study carried out in Latin America, revealed a high prevalence of severe acute-on-chronic liver failure (ACLF) among hospitalized patients with acute decompensation of cirrhosis. Notably, individuals with a greater proportion of Native American ancestry (and reported race) showed a higher risk of 28-day mortality compared to those of European and African descent.The study, published in Gastroenterology, highlighted the importance of considering genetic ancestry and race in liver disease research. It involved 1274 patients across 7 Latin American countries and found associations between social factors, organ function markers, and short-term mortality. Additionally, higher Native American ancestry correlated with ACLF development, independent of alcohol-related hepatitis and bacterial infections.

Read more on our website

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Contributing to EASL Clinical Practice Guidelines on ACLF

Read more on our website

Antimicrobial stewardship and effective use of empirical antibiotic treatment

On World Antimicrobial Resistance Week 2023, we emphasized the need for implementation of evidence-based antimicrobial stewardship programs in the management and care of patients with acutely decompensated cirrhosis and ACLF to improve the use of antimicrobial agents and reduce the antimicrobial resistance rate, all while ensuring positive patient outcomes.

EF CLIF researchers contributed to the EASL Clinical Practice Guidelines on ACLF published in Journal of Hepatology. These guidelines consist of a set of statements with recommendations intended to optimize care for patients with ACLF. Officially presented at the EASL Congress 2023 in Vienna, Austria, the EASL Clinical Guidelines on ACLF aim to assist clinicians to recognize the syndrome, make triage decisions, identify and manage acute extrahepatic precipitants (including, but not limited to, bacterial and fungal infections), identify organ systems requiring support or replacement, define potential criteria for futility of intensive care, and identify potential indications for liver transplantation.

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Metabolomic models for ACLF prediction

Read more on our website

Two new prognostic models based on three metabolites reflecting systemic inflammation, mitochondrial dysfunction and sympathetic nervous system activation were found to better predict short-term mortality in acute decompensation of cirrhosis and ACLF. The study, published in Gut, identified three metabolites with the potential to improve prognosis in patients with acute decompensation of cirrhosis and ACLF at high risk of short-term mortality. EF CLIF researchers designed and validated two metabolomic models (CLIF-C MET). Model 1 incorporates three prognostic metabolites and age, while Model 2 includes these metabolites along with bilirubin, INR, and age, increasing prognostic accuracy.

Watch Jonel Trebicka (picture), Emmanuel Weiss and Carlos de la Peña on this Gut video abstract

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New insights on the role of albumin in cirrhosis

Read more on our website

A new study highlighted the protective role of albumin in preserving mitochondrial ultrastructure and function during inflammation resulting from liver injury.In the study, published in FASEB Journal, researchers from the ENTR-CLIF investigated the role of albumin in maintaining mitochondrial homeostasis during inflammation. Using a mouse model of TNFα-induced liver injury, liver slice cultures, and isolated hepatocytes from wild-type mice, they provided new insights into albumin's potential protective mechanisms against oxidative stress and its contribution to liver function.

First author of the paper Marta Duran-Güell. Picture: © Marta Duran-Güell.

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Protective effect of omega-3 lipid mediators in MAFLD

Read more on our website

A study in mice carried out by researchers of the ENTR-CLIF in collaboration with the Barcelona Biomedical Research Institute (Spain), Massachusetts General Hospital and Harvard Medical School (MA, USA), and RIKEN Center for Integrative Medicine Sciences and Keio University (Japan), highlighted the role of lipid bioactive products of omega-3 polyunsaturated fatty acid (PUFA) in helping preserve hepatocyte mitochondria function and mitigating the pathophysiological effects associated with metabolic-associated fatty liver disease (MAFL). The study, published in Hepatology, provided the mechanistic basis by which transgenic fat-1 mice, become resistant to liver disease and likely other inflammatory diseases characterized by mitochondrial dysfunction.

First author of the paper Cristina López-Vicario. Picture: © Cristina López-Vicario.

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A liver dialysis device for treatment of cirrhosis and ACLF

Read more on our website

First-in-human clinical trial of DIALIVE, a liver dialysis device, met safety requirements and showed improvement of pathophysiological markers of chronic liver disease reducing time to resolution of acute-on-chronic liver failure (ACLF) compared to standard of care.The study, published in Journal of Hepatology, revealed that a proportion of patients treated with DIALIVE resolved ACLF faster than those receiving standard of care, and patients that resolved remained free of ACLF for 28 days after only 3 days of treatment.

This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement no. 733057.

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Guiding effective COVID-19 vaccination strategies

Read more on our website

Collaborative study of the EASL-CLIF Consortium found that people with chronic liver disease and post-liver transplantation are at higher risk of getting infected with SARS-CoV-2 after COVID-19 primary series vaccination and identified predictive factors associated with breakthrough infection.The study, published in Hepatology Communications, revealed the heterogenous response to COVID-19 vaccine primary series among individuals with cirrhosis, patients with autoimmune liver disease without cirrhosis, and liver transplant recipients. Researchers identified factors predicting poor vaccine response and risk of breakthrough infection in these populations compared to healthy individuals with no prior COVID-19 infection or human immunodeficiency virus infection.

This research was supported by

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Foundation for Liver Research

European Society for Organ Transplantation–European Liver and Intestine Transplant Association (ESOT–ELITA)

European Liver Patients' Association (ELPA)

European Association for the Study of the Liver (EASL)

Removing barriers to access liver transplantation

Liver transplantation in severe ACLF - A global challenge

Read more on this Behind CHANCE story

Read more on this Behind CHANCE story

When the team at Hospital das Clínicas in Brazil recruited the 500th patient in the CHANCE study, we asked Patricia Momoyo what it takes to staying on top of patient recruitment. Her previous experience in the ACLARA study was key to achieve this milestone.

The team led by Professor Alberto Farias at at Hospital das Clínicas, Brazil, continued ahead of patient recruitment achiving the recruitment of patient no. 1000. We caught up with him at The Liver Meeting® to learn more about bringing change to the liver transplantation landscape.

Professor Flair Carrilho (left) and Patricia Momoyo (right) at the EASL Congress 2023. Picture: © EF CLIF.

Professor Alberto Farias (left) and Cristina Sánchez-Garrido (right) at TLM 2023. Picture: © Alberto Farias.

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"The CHANCE study will allow us to better understand the outcomes of patients with ACLF and provide us with better tools for listening of these patients in the future."Nadia Selzner, MD

"We admire what you do and we are grateful to you for letting us be part of this project."Margarita Anders, MD

"Trying to create a policy to help the hopeless patients because hope is the last thing ever lost."Prasun Jalal, MD

"The CHANCE study is a unique opportunity to clarify which patients will benefit from liver transplantation, and to help clinical decisions!"Laure Elkrief, MD

"We think that the CHANCE study will help better understand the natural history of ACLF, to define the benefit of liver transplantation and futility criteria."Giovanni Perricone, MD

"With and improved understanding of the factors that impact transplant candidacy assessment and post-transplant outcomes, we can be better advocates for our patients."

Christina Lindenmeyer, MD

"We are confident that the CHANCE study will be a game changer in the management of ACLF."Sebastián Marciano, MD

What our collaborators worldwide say...

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"Team Lisboa is very happy to be part of an international forum of study and debate of critical liver disease."Luis Bagulho, MD

"For us, CHANCE is a unique opportunity to explore the impact of liver transplantation on patients with severe ACLF."Thierry Gustot, MD, PhD

"As a team we are motivated and proud to be contributing to this global study which will benchmark treatment of patients with ACLF."Rachel Westbrook, MD

"An unrepeatable investigation looking for a therapeutic window for liver transplantation in ACLF."Javier Fernández, MD, PhD

"Grateful to be part of an international team and hopefully giving CHANCE to our sickest liver patients."Mónica Sousa, MD

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AI solutions for liver transplant organ allocation in Europe

The EU-funded LEOPARD project, of which EF CLIF is a proud participant, started in November 2023 to develop modern artificial intelligence-based solutions for organ allocation in liver transplantation.Coordinated by Christophe Duvoux at Assistance Publique–Hôpitaux de Paris, France, the consortium includes organ-sharing organisations (OSOs), as well as 50 liver transplantation centers, major key opinion leaders in the field of hepatology, liver oncology, liver surgery and liver transplantation, statisticians, research labs, small and medium-sized enterprises, and patient organizations. LEOPARD will explore and prospectively validate advanced, second and next-generation predictive algorithms in liver transplant candidates which will be offered to participating OSOs to improve outcomes, reduce mortality on the waiting list, and harmonize offering schemes across Europe.

Find out more on the LEOPARD project website

LEOPARD Consortium:

This project has received funding from the EU's Horizon Europe program under grant agreement no. 101080964.

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Connecting and engaging with the hepatology community

Celebrating 10 years of the first evidence-based diagnostic criteria for ACLF

CANONIC, and acronym for European Association for the Study of the Liver (EASL)–Chronic Liver Failure (CLIF) Consortium acute-on-chronic liver failure in cirrhosis, was unprecedented in its scope and findings, providing the means for the first evidence-based definition of the syndrome referred to as "acute-on-chronic liver failure" (ACLF). Although no universal definition of ACLF has been yet recognized, the EASL-CLIF Consortium diagnostic criteria has been applied and validated worldwide.Our campaign, #CANONIC10years, was initiated to commemorate the groundbreaking findings of the CANONIC study, which have paved the way for further advancements in liver disease research.

Watch Richard Moreau on #CANONIC10years

Watch Minneke Coenraadon #CANONIC10years

Watch Laure Elkriefon #CANONIC10years

Watch Vicente Arroyo on #CANONIC10years

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Contributing expert opinions on chronic liver disease

In EASL Studio Season 4, Episode 17, Albumin in cirrhosis: For all, for some, for none, Professor Joan Clària who serves as the Director of the Grifols Chair provided his insights on the mechanisms of action of albumin in health and chronic liver disease. This episode also counted with the expert opinion of Professor Paolo Caraceni, Clinical Trial Coordinator in the DECISION project.

Under the theme EASL – EF CLIF and EU grants: Exploring novel mechanisms and treatment of chronic liver failure, EASL Studio Season 4, Episode 14 featured Coordinator of the DECISION project Professor Pierre-Emmanuel Rautou, Communications Lead for the MICROB-PREDICT project Professor Minneke Coenraad, and Clinical Trial Coordinator of the A-TANGO project Dr. Cornelius Engelmann.

EASL Studio Season 4, Episode 2, YI choice: How to build consortia and registries, featured a guest appearanced by former Scientific Director of EF CLIF Professor Rajiv Jalan who shared his view on the key factors to the successful establishment and consolidation of a research consortium.

Watch on EASL Studio

Watch on EASL Studio

Watch on EASL Studio

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Supporting independent investigator-led research and innovation

The Sample and Data Usage Committee offers independent researchers at all career stages the opportunity to access and use clinical and omics data, as well as samples collected from flagship studies funded by EF CLIF, including CANONIC, PREDICT, ACLARA, COBALT, and CHANCE. Indepent investigator-led ancillary studies approved by the Sample and Data Usage Committee in the year ended 31 December 2023 are: Prognostic value of neutrophil-to-lymphocyte ratio as a marker of immune dysfunction in ACLF PI: Rosa Martin Mateos, Hospital Universitario Ramón y Cajal, Spain

Association of 1,3-beta-D-glucan detection in different body fluids with gastrointestinal leakage and outcome in patients with ACLFPI: Florian van Bömmel, University of Leipzig, GermanyEvaluating the impact of cardiopulmonary complications in cirrhosis and ACLF: Hepatopulmonary syndrome, portopulmonary hypertension and cirrhotic cardiomyopathy/diastolic dysfunction PI: Eric Trépo, CUB Hôpital Erasme, Université Libre de Bruxelles, BelgiumDecoding prognostic trajectories in decompensated cirrhosis without ACLF: A machine learning approach

PI: Eric Trépo, CUB Hôpital Erasme, Université Libre de Bruxelles, Brussels, BelgiumEvaluation 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, SpainHeart rate and blood pressure parameter dynamism, as digital markers to determine progression of acute decompensation of cirrhosisPI: Rajeshwar Prosad Mookerjee, University College London, UK

Find out more about the EF CLIF database

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Scientific publications

Articles

Open Access Pulmonary impairment independently determines mortality in critically ill patients with acute-on-chronic liver failureLiver Int 2023, 43(1): 180–193Open Access Essential role for albumin in preserving liver cells from TNFα-induced mitochondrial injuryFASEB J 2023, 37(3): e22817Open Access Genetic ancestry, race, and severity of acutely decompensated cirrhosis in Latin AmericaGastroenterology 2023, 165(3): 696–716Open Access Serological response and breakthrough infection after COVID-19 vaccination in patients with cirrhosis and post-liver transplantHepatol Commun 2023, 7(11): e0273

Open Access Randomized, controlled clinical trial of the DIALIVE liver dialysis device versus standard of care in patients with acute-on- chronic liver failureJ Hepatol 2023, 79(1): 79–92

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Essential lipid autacoids rewire mitochondrial energy efficiency in metabolic dysfunction-associated fatty liver diseaseHepatology 2023, 77(4): 1303–1318Novel prognostic biomarkers in decompensated cirrhosis: A systematic review and meta-analysisGut 2023, 73(1): 156–165Open Access Sympathetic nervous activation, mitochondrial dysfunction and outcome in acutely decompensated cirrhosis: the metabolomic prognostic models (CLIF-C MET)Gut 2023, 72(8): 1581–1591

Clinical Practice Guidelines

Open Access EASL Clinical Practice Guidelines on acute-on-chronic liver failureJ Hepatol 2023, 79(2): 461–491

Editorial

Attitudes toward liver transplantation for ACLF-3 determine equity of accessJ Hepatol 2023, 78(3): e93–e95

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Reviews

Intensive care management of acute-on-chronic liver failureIntensive Care Med 2023, 49(8): 903–921Open Access Extracorporeal liver support and liver transplantation for acute-on-chronic liver failureLiver Int 2023Open Access Acute-on-chronic liver failure: Current interventional treatment options and future challengesJ Pers Med 2023, 13(7): 1052Open Access Mechanisms of immunity in acutely decompensated cirrhosis and acute-on-chronic liver failureLiver Int 2023

Open Access Roles of systemic inflammatory and metabolic responses in the pathophysiology of acute-on-chronic liver failureJHEP Rep 2023, 5(9): 100807

efclif.com

"The ENTR-CLIF is the perfect fit for EF CLIF as it brings expertise to process large datasets from high-throughoutput techniques, apply modeling methods and identify novel biomarkers to better understand liver disease progression and response to treatment."

The research activities of the ENTR-CLIF centers are carried out under the lead of the Director of the Grifols Chair. We fund laboratory-based researchers within our network of 23 centers including research organizations, universities, and industry.

Professor Joan ClàriaDirector of the Grifols Chair

"I believe that the EASL-CLIF Consortium is a fundamental network for conducting high-quality research in chronic liver disease and acute-on-chronic liver failure. It stands as a pioneering example of a research network achieving remarkable results in this field."

We welcome three new centers to join the EASL-CLIF Consortium

Professor Paolo AngeliChair of the EASL-CLIF Consortium Steering Committee

University Clinic of Gastroenterohepatology, MacedoniaKoç University Hospital, TurkeyHospital Clínico Universitario de Valencia, Spain