BARCELONA—The 5th MICROB-PREDICT General Assembly meeting took place in Budapest, Hungary, from 17 to 19 January 2023. Partners from 16 institutions in 10 countries met to review progress within MICROB-PREDICT and set the ALB trial up for success.

BARCELONA—Acute-on-chronic liver failure is a syndrome associated with high short-term mortality and characterized by multiple organ failures and excessive systemic inflammation that occurs in one third of the patients hospitalized for acute decompensation of cirrhosis. A new study shows that when used in combination, granulocyte-colony stimulating factor (G-CSF) and TAK-242, an inhibitor of Toll-like receptor-4 (TLR-4), inhibit inflammation and promote hepatocyte regeneration in two mouse models of ACLF. The study published on 1 November 2022 in Journal of Hepatology, provides evidence of the effectiveness of this drug combination and its potential to be repurposed for the treatment of ACLF.

BARCELONA—While liver transplantation is the most effective treatment available for patients with ACLF-3, access to liver transplantation for these critically ill patients with underlying cirrhosis and multiorgan failures varies greatly across countries and transplant centers in each country. Barriers to access to liver transplantation may include admission to the intensive care unit, referral to a tertiary hospital, timely organ allocation, and listing for liver transplant. Access to liver transplantation for patients with ACLF-3, although, requires agreement between all members of the transplant team, but also health professionals at primary and secondary centers should be aware of liver transplantation as potential treatment for patients with cirrhosis that require critical care.

BARCELONA—On 17 November 2022, our collaborators at Hospital das Clínicas da Universidade de São Paulo in Brazil recruited patient no. 500. Provided sufficient data, this will allow us to conduct an interim assessment and guide future directions in the study.

BARCELONA—Multidrug-resistant bacterial infections constitute an increasing healthcare problem that negatively impacts survival of patients with liver disease. Strategies to prevent the spread of antimicrobial resistance in liver disease, particularly decompensated cirrhosis and acute-on-chronic liver failure (ACLF), should be urgently addressed.

BARCELONA—The 3rd CHANCE Investigator Meeting took place in Washington D.C., USA, on the occasion of the 73rd Annual Meeting of the American Association for the Study of Liver Diseases (ASSLD). The CHANCE investigator meeting brought together 46 investigators and professionals from 10 countries (Argentina, Canada, France, Germany, India, Italy, Spain, The Netherlands, UK, and USA), 34 people attended in person and 12 joined online, to review and discuss project progress, share experiences and address challenges of patient recruitment.

Target group: Liver and transplant surgeons, hepatologists, intensive care specialist, transplant anaesthesiologists, transplant fellows.

BARCELONA—The 4th DECISION General Assembly meeting took place in Madrid, Spain, from 19 to 21 October 2022. This meeting brought together partners from 21 institutions and industry in 10 countries to review progres and discuss further about most recent results leading to biomarker candidates that can better predict prognosis of acute decompensation of cirrhosis. With the aim to develop novel therapeutic approaches to treat cirrhotic patients that develop acute-on-chronic liver failure (ACLF), the COMBAT trial within DECISION will evaluate safety of most promissing drug combinations identified through data-driven approaches and validated in pre-clinical studies using animal models of liver disease.

BARCELONA—The Inspiring and Writing Group works across disciplines and brings together expertise in end-stage liver disease, liver transplantation, critical care, gut microbiome, hepatic vascular disorders, hepatic encephalopathy, acute kidney injury, and liver regeneration. On the first face-to-face meeting of the Inspiring and Writing Group, members which project proposal was successful in an internal call, presented the rationale behind their project and expected outcomes.

At the European Foundation for the Study of Chronic Liver Failure (EF CLIF), we belief that incorporating the patients' perspective in clinical research is critical to ensure that the research outcomes we measure reflect those which are most relevant to patients. Within the European Union-funded projects we coordinate, namely, MICROB-PREDICT, DECISION and A-TANGO, the European Liver Patients' Association (ELPA) is involved as a partner with representation in several stakeholder groups and committees of all three consortia.

Our target of recruiting 2,000 patients is still far behind, but with more active centers joining every month and the collective effort of all the centers that are already open across the world, we are certain that we will reach our goal soon.

Ignacio Calero was a member of our Board of Trustees since the establishment of the European Foundation for the Study of Chronic Liver Failure (EF CLIF) in 2015.

Newly appointed Regional Coordinators for North America, Constantine Karvellas (University of Alberta, Canada) and Ruben Hernaez (Michael E. DeBakey Veterans Affairs Medical Center, TX, USA), will be officially introduced to all CHANCE Investigators at this event.

The European Day of Donors and Foundations is an initiative to celebrate the role of philanthropy at the European level and raise public awareness about the value of civic action.

We were pleased to welcome Principal Investigator of the ACLARA study, Prof. Flair José Carrilho, this month at the EF CLIF Headquarters in Barcelona. During his visit, he met with Prof. Vicente Arroyo, Director of EF CLIF, and Prof. Richard Moreau, Emeritus Researcher at the French Institute of Health and Medical Research (INSERM), Consultant in Hepatology at Hôpital Beaujon, France, and Honorary Director of the Grifols Chair at EF CLIF, who acted as Principal Investigator for Europe for the ACLARA study. They hold long meetings with our data managers, biostatisticians and bioinformaticians to discuss further about the results of the ACLARA study and polish a manuscript that will be submitted shortly for publication.

BARCELONA—Liver transplantation appears to be the most effective treatment for patients with ACLF-3. Yet, in practice, liver transplant is not widely used in Europe for treatment of these patients for being considered to be too sick.

BARCELONA—Recruitment of 1159 patients ended in September. Sponsored by the European Foundation for the Study of Chronic Liver Failure (EF CLIF), the COBALT study – COVID-19 vaccination and biomarkers in cirrhosis and post-liver transplantation – will compare responses after dose 2 and dose 3 of the COVID-19 vaccine in patients with cirrhosis, following liver transplantation or autoimmune liver disease, with healthy subjects as a control group. The level of antibody response, the durability of the response and degree of protection against COVID-19 will be also assessed.

BARCELONA—The emergence of new variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) over the last two years has represented a serious challenge for healthcare professionals and liver patients worldwide. The B.1.1.529 (omicron) SARS-CoV-2 variant, being more transmissible and resistant to neutralization, rapidly displaced the B.1.617.2 (delta) variant. Besides omicron infection appears to be associated to milder symptoms, preliminary data on omicron natural immunity were still inconsistent by the time EASL position statements were published. The updated EASL position paper, although, provides a comprehensive review of liver-specific effects of COVID-19 infected patients with chronic liver disease, hepatobiliary cancer, and after liver transplantation.

We took this opportunity to enhance our brand position and reflect on our fundamental aspiration to become a global reference in the field of chronic liver disease. Our brand proposition now incorporates elements that will contribute to make a positive impact on the liver community and beyond.

LONDON—Since its foundation in 2009, the EASL-CLIF Consortium has been devoted to the advancement of knowledge on the pathophysiology, diagnostics, and treatment of cirrhosis.

LONDON—The 2nd CHANCE Investigator Meeting took place in London, UK, during the celebration of the International Liver Congress 2022 organized by the European Association for the Study of the Liver (EASL). This event brought together 49 investigators and professionals from 18 countries (Argentina, Belgium, Brazil, Czech Republic, France, Germany, India, Italy, Japan, Poland, South Korea, Spain, Switzerland, Taiwan, The Netherlands, Turkey, UK and USA), 27 people attended in person and 22 joined online.

LONDON—Within the European Foundation for the Study of Chronic Liver Failure (EF Clif), the EAS-CLIF Consortium Steering Committee oversees the research activities of the EASL-CLIF Consortium, a network of more than 100 tertiary care and university hospitals in 28 European countries.

LONDON—Within the framework of the EASL Chair activities, every year members of the EASL-CLIF Consortium reunite to discuss progress of current clinical studies and set out the impacts of the achievements during the former year. This meeting was originally planned as an in-person event at ExCeL London at the start of the International Liver Congress 2022 organized by the European Association for the Study of the Liver (EASL), but finally took place online due to the 2022 UK railway strike. In order to facilitate participation, the EF Clif management support team made the necessary arrangements to ensure a successful meeting.

BARCELONA—Cirrhosis and chronic liver disease are associated with dysregulation of the immune system. Previous studies have demonstrated that patients with cirrhosis are at increased risk of death from COVID-19, but few data exist on immunity following vaccination in cirrhosis and post-liver transplant patients. Recent findings from researchers at the European Foundation for the Study of Chronic Liver Failure (EF CLIF) and collaborators in Spain, Italy, the Netherlands and UK provide evidence of the effectiveness of the vaccine in patients with cirrhosis, autoimmune liver disease or post-liver transplantation.

Do not miss this opportunity to meet and discuss progress on the EASL-CLIF Consortium activities in this meeting chaired by Paolo Angeli, Chair of the EASL-CLIF Consortium Steering Committee, and Rajiv Jalan, Scientific Director of the European Foundation for the Study of Chronic Liver Failure (EF Clif).

A special session at the ILTS 2022 focused on acute-on-chronic liver failure prognosis and put liver transplantation and organ allocation policy into perspective. An event hosted by ILTS President Marina Berenger (Hospital Universitario La Fe, Spain) and Program Chair, ILTS President-elect Mohamed Rela (Dr. Rela Institute and Medical Center, India), where Rajiv Jalan presented the design and progress of the CHANCE study.

BARCELONA—The A-TANGO General Assembly meeting brought together early career researchers, industry experts and leading clinical researchers participating in this project to review progress and celebrate the achievements accomplished to date.

Investigators of the CHANCE study are invited to attend to the CHANCE Investigator Meeting that will be held in-person and online on 24 June 2022 12:00–13:30. In celebration of the International Liver Congress 2022 in London, UK, organized by the European Association for the Study of the Liver (EASL), this extraordinary meeting will take place at ExCeL London, South Gallery 27.
Preliminary data will be presented and regional coordinators will share their insights. The EF Clif General Manager will also explain how to submit any proposals for ancillary studies that may derive from the CHANCE study.

BARCELONA—The establishment of the Scientific Advisory Board (SAB) represents a step forward in the consolidation of the Euroepean Foundation for the Study of Chronic Liver Failure (EF CLIF). The SAB is constituted by 12 members that will meet every year to review EF CLIF activities and draft a report highlighting areas of improvement and recommendations for further development.

BARCELONA—The 5th DECISION Steering Committee meeting was a two-day event where work package leaders presented preliminary results after one year and half of dedicated work and extensive analysis.

BARCELONA—Members of the MICROB-PREDICT consortium met in Mallorca, Spain, to present and discuss most recent results establishing the foundations for the upcoming ALB-TRIAL, a clinical trial to be conducted in 8 European centers that will validate biomarkers for decompensated cirrhosis and acute-on-chronic liver failure (ACLF) in response to albumin treatment.

BARCELONA—Bacterial infections can cause severe complications in the clinical course of cirrhosis and ensuring adequate antimicrobial treatment is crucial to prevent associated complications and improve survival of patients with advanced liver disease. As cirrhosis progresses, liver function gradually deteriorates. Liver dysfunction results in hypoalbuminemia and in changes in bile acid synthesis in hepatocytes which in turn may alter the pharmacokinetic properties of certain drugs. Published on 18 February 2022 in Journal of Antimicrobial Chemotherapy, this study provides evidence of variations in the distribution and excretion of tigecycline, a broad-spectrum antibiotic frequently used for the treatment of severe bacterial infections in critically ill patients with and without cirrhosis.

BARCELONA—Albumin administration has been proven to be an effective therapy for patients with acute decompensation of cirrhosis. Albumin, the most abundant protein in the bloodstream, is synthesized by the liver and its high affinity for fatty acids allows for the transport of lipids that serve as substrates for the synthesis of membrane phospholipids and some bioactive compounds. In advanced liver disease, post-translational modifications of albumin may result in changes in its lipid content and thus alter the circulating lipid profile.

BARCELONA—Acute-on-chronic liver failure (ACLF) is a syndrome that develops in 30% of the patients hospitalized due to cirrhosis. About 30% of patients with ACLF will die within 28 days of hospital admission. Pioneering studies by the European Foundation for the study of Chronic Liver Failure (EF Clif) have been of paramount importance in defining new criteria for the diagnosis and prognosis of ACLF and addressing the underlying mechanisms that contribute to acute hepatic decompensation, multiorgan failure, and high risk of short-term mortality.

Acute-on-chronic liver failure (ACLF) was recently described as a syndrome that leads to acute hepatic decompensation, multiorgan failure and a high risk of short-term mortality. Most common precipitating factors in ACLF, include bacterial infections, alcoholism and persistence and reactivation of viral hepatitis, although for some patients neither of these are observed. Current treatment strategies include organ support, liver transplantation and immunomodulating therapy, yet the mechanisms underlying ACLF remain unclear and the needs for critically ill patients with cirrhosis unmet.

BARCELONA—Currently, antibiotic resistance represents a major concern for patients with cirrhosis. Previous work suggested that colonization by multidrug-resistant bacteria increases the risk of resistant infections in non-cirrhotic patients. New research in two geographically distinct cohorts in Europe by a team at the European Foundation for the Study of Chronic Liver Failure (EF Clif), Hospital Clinic de Barcelona and Goethe University Frankfurt shows that rectal colonization by antibiotic-resistant bacteria is a frequent and clinically relevant problem in patients with cirrhosis requiring critical care. The type of colonizing bacteria was found to be heterogeneous between centers. This study provides evidence that rectal colonization by antibiotic-resistant bacteria is associated with high risk of infections by the colonizing strain in cirrhotic patients admitted to the intensive care unit. Therefore, early detection of resistant carriers opens up the possibility for targeted antibiotic therapies and rapid isolation strategies. These measures in combination may contribute to reduce the spread of antibiotic resistance among hospitalized patients with cirrhosis. This work was published on 22 January 2022 in Journal of Hepatology.

BARCELONA—End-stage chronic liver disease, also named decompensated cirrhosis, is a major cause of morbidity and mortality and represents a global burden. The epidemiology of cirrhosis is undergoing demographic changes due to the prevalence of overweight and obesity, and new emerging treatments for hepatitis C. However, limited evidence is available on the profile of cirrhosis in Germany. Researchers at the Goethe University Hospital Frankfurt led by Prof. Jonel Trebicka analyzed the data from the Federal Statistical Office of Germany of around 250 million hospital admissions in Germany from 2005 to 2018 and found that the number of hospital admissions due to cirrhosis has increased nationwide and its diagnosis as comorbidity doubles the mortality rate of other chronic diseases. This work was published on 4 November 2021 in The Lancet Regional Health - Europe.

The CHANCE study is a close collaboration between EFCLIF, ELITA and ILTS and aims to evaluate in its entirety the role of liver transplantation for patients with advanced Grades of acute on chronic liver failure (ACLF). It was exciting to see that 3-centres (Argentina: 2; UK:1) had got the study underway and 17-patients had already been recruited

BARCELONA—The 3rd DECISION General Assembly Meeting was a three-day event where work package leaders presented major outcomes and milestones of the DECISION project.

BARCELONA—The results obtained with the CHANCE study could contribute to the drafting of new protocols for clinical action for patients with different acute-on-chronic liver failure grades, improve the criteria for assigning organs to these patients, compare survival rates according to severity and establish the impact of liver transplantation on their quality of life.

BARCELONA— The European Association for the Study of Chronic Liver Failure (EASL-Clif) Consortium is constituted by more than 300 clinical researchers in 116 university hospitals across 28 countries. Since its foundation in 2009, the EASL-Clif Consortium has been devoted to the advancement of knowledge on the pathophysiology, diagnostics, and treatment of cirrhosis.

BARCELONA—The EASL-Clif Consortium was founded in 2009 with the aim to strengthen collaboration across Europe and further our understanding of advanced liver disease. Pioneering work by researchers and professionals in 106 centers in 26 European countries led to the description of acute-on-chronic liver failure (ACLF) – a syndrome that affects patients with cirrhosis characterized by acute decompensation, associated with organ failures and high short-term mortality.

Cirrhosis has a huge impact in the quality of life of patients and the healthcare and economic systems. The EF Clif researchers have contributed to characterize and find the predictors and mechanisms involved in the development and clinical course of ACLF, which will help to prevent and treat ACLF in a near future.

BARCELONA—Working closely with the Scientific Board and Scientific Coordinators, the DMC plays an important role in the design and development of the databases and protocols for all EF Clif studies, ensures good research data management, assists regional coordinator with protocol implementation, tracks specimen information, delivers remote training across study sites, and contributes to data analysis and manuscript preparation.

BARCELONA—Some patients with alcoholic liver disease develop alcoholic hepatitis which eventually results in multiorgan failure and death. End-stage liver disease may lead to acute-on-chronic liver failure (ACLF), a syndrome characterized by acute decompensation of cirrhosis, organ failures, and high short-term mortality. There is no specific treatment for patients with ACLF and management is based on organ support and liver transplantation. The A-TANGO project aims to address unmet clinical needs for patients with ACLF and improve patient survival rates by means of a novel combinatorial therapeutic strategy – G-TAK improves hepatocyte proliferation through granulocyte colony-stimulating factor (G-CSF) and reduces systemic inflammation by repurposing TAK-242, an antagonist of Toll-like receptor 4. A multicenter phase II clinical trial will be conducted to assess the effectiveness and therapeutic benefits of G-TAK.

The CARBALIVE Consortium has announced that the Phase 2 clinical trial has obtained positive data on efficacy of Carbalive™, a product candidate for the treatment of patients with decompensated cirrhosis.

The Consortium is developing and testing a novel blood filtration system, DIALIVE, whose design is based on 20 years of research led by Professor Rajiv Jalan, Professor Nathan Davies and members of the Liver Failure Group at UCL. Yaqrit Ltd was spun off from UCL in 2014 to develop and potentially commercialise treatments including Dialive™ for patients with advanced liver disease. Professor Jalan is the lead scientific founder of Yaqrit.

Download list of CHANCE centers

University Hospital Dubrava, led by Ivica Grgurevic; Charite University Hospital in Berlin, by Cornelius Engelmann; Laiko General Hospital of Athens, by George Papatheodoridis; Liver Unit. University of Verona, by Davide Sacerdoti; Centre Hospitalier de Luxembourg, by Verónica Prado; Hospital de Santa Luzia in Viana do Castelo, by Rogerio Corga; Università della Svizzera Italiana, by Roberto di Donato and Sakarya University School of Medicine, by Aydin Seref Köksal are the new members.

We want you to know us and our partners better. We are proud of the research projects on going and the ones that are coming.

The trial is endorsed by the EF Clif and has engaged four hospitals in the area of Barcelona: Hospital Clinic, Hospital de Bellvitge, Hospital del Mar and Hospital Germans Trias i Pujol.

For the next 5.5 years, Prof Pierre-Emmanuel Rautou will coordinate 21 relevant European institutions to analyse and integrate data and biological samples from 2,000 patients, validate the results in animal models and test the most promising resultant therapy in a phase II clinical trial.

He also has vast expertise in leading collaborative international projects such as the EU H2020 ALIVER and CARBALIVE. Together with Prof. Vicente Arroyo, Director of the EF Clif, they will lead the Strategic Research Program of the Foundation.

In the premises of the Fondazione Cini, a small island in front of the world famous Piazza San Marco, the most active members of the Clif Consortium and other outstanding researchers from around the world attended the two-day Symposium entitled "The Acute-on-Chronic Liver Failure syndrome in cirrhosis".

He has joined the EF Clif to conduct a research on the characteristics of different organ failures in patients with acutely decompensated cirrhosis, using the metabolomics data from the CANONIC Study cohort, under the auspices of the Grifols Chair during the next 6 months.

Dr Weiss is a member of the Anesthesiology and Critical Care Unit in Hôpital Beaujon in Clichy (France) and an Associate Professor in Liver and Digestive ICU at the same hospital. He has specialized in innate immune response and organ failure of patients with liver disease. He is also young editor of Intensive Care Medicine, the Journal of the European Society of Intensive Care Medicine.

The signature of the first collaboration agreement between Grifols and the Fundació Clínic per la Recerca Biomédica (FCRB, participated by the Universitat de Barcelona and the Hospital Clínic) on June 11th, 2009, provided the grounds and funds to establish an initial consortium constituted by 70 University Hospitals from all across Europe.

Most of the EASL Clif Consortium centres were represented and active in the Congress. Thanks to the daily work of the Consortium members, the quality of their contributions in oral presentations, posters and a Think Tank on Chronic Liver Failure were highly appreciated and commented during the meeting.

During the several working sessions, more than 60 people including clinicians, molecular scientists, bioinformaticians, data managers and nurses, discussed about the different work-packages and milestones, in an attempt to perfectly coordinate the work of the 22 institutions which are part of the project.

The first inclusion week of the Aclara study finished with two new patients recruited in Hospital das Clinicas of Sao Paulo University.

24 professionals from Brazil, Colombia, Panama, Mexico and Peru attended the sessions On 30th and 31st of October 2018 where they were trained in the Management of samples, completion of the eCRF and use of the Clif-Consortium scores.

The first session served as an introduction to the management of the samples, followed by onother one focused on the protocol guidelines and the use of the Clif-Consortium scores

The discussion was focused on coordinating the efforts into reaching common act policies. Headed by the PIS of the Study, Dr Flair Carrilho, Dr Vicente Arroyo and Dr Richard Moreau and with the assistance of Dr Alberto Q Farias, the Study coordinator, the meeting was also instrumental to work further on different technical aspects and establish further guidelines of the ACLARA STUDY.

The last member to join the project has been Hospital de las Clínicas de Asunción (Paraguay) in December '18.

Dr Wenji Gu is a medical investigator, currently finishing her Master at the Department of Gastroenterology in Ren Ji Hospital, School of Medicine, and at Key Laboratory of Gastroenterology & Hepatology in Shanghai Jiao Tong University.

The change is aimed to prepare the Foundation to major challenges coming in the near future, including a significant increase in the number of projects and funds, the participation of the Foundation in EU grants and the incorporation of high throughput omics technology in most observational studies and projects.

More than 80 investigators of the EASL Clif Consortium took part in the Assembly where the speakers gave a comprehensive overview of the latest researches in the setting of EF Clif and had the opportunity to exchange experiences.

Among the participants, there were most Steering Committee Members of the EASL-CLIF Consortium, a selected group of investigators from the PREDICT Study, the Principal Investigators of the 2018 research program of the EF Clif, members of the Grifols Chair, Dr Tom Henning Karlsen, EASL General Secretary, Professors Roger Williams and Flair Carrilho

The incorporation for both candidates is foreseen during the first quarter of 2018

The CANONIC study has shown that among patients with acute decompensation (AD) of cirrhosis, those who had Acute-on-Chronic Liver Failure (ACLF, characterized by intense systemic inflammation, organ failures and poor outcome) were clearly distinct from those with traditional AD (who do not have organ failures and have good outcome).