EF CLIF | European Foundation for the study of chronic liver failure

NEWS&EVENTS

November 30, 2023 Celebrating 10 years of CANONIC: A paradigm shift in chronic liver disease research To celebrate 10 years since the publication of the results from the CANONIC study, we talked with Prof. Vicente Arroyo, senior author in the paper published in Gastroenterology, to discuss about the past, present and future of chronic liver disease research.

The CANONIC study – European Association for the Study of the Liver (EASL)–Chronic Liver Failure (CLIF) Consortium acute-on-chronic liver failure in cirrhosis – was the first large, prospective study ever conducted aimed at establishing a definition for acute-on-chronic liver failure (ACLF). Prof. Arroyo is internationally renowned for his research liver disease and inflammation.

November 18, 2023 World AMR Awareness Week 2023 The World AMR Awareness Week (WAAW) is a global campaign to raise awareness and understanding of antimicrobial resistance and promote best practices among One Health stakeholders (i.e., the ultimate beneficiaries – people, animals and the environment – and the organizations that work to protect them) to reduce the emergence and spread of drug-resistant pathogens, and ensure health and food safety. World AMR Awareness Week is celebrated from 18–24 November every year.

Antimicrobial resistance (AMR) occurs when bacteria, viruses, fungi and parasites no longer respond to antimicrobial agents. As a result of drug resistance, antibiotics and other antimicrobial agents become ineffective and infections become harder or impossible to treat, increasing the risk of disease spread, severe illness and death.

November 15, 2023 Behind CHANCE: The team lead by Prof. Alberto Farias at Hospital das Clínicas da Universidade de São Paulo – the largest healthcare center in Latin America and the most active liver transplantation center in Brazil – recruited the 500th patient in the CHANCE study one year ago, and has continued to be ahead of patient recruitment helping us reach the 1000th patient milestone.

At our 6th CHANCE Investigator Meeting in Boston, MA, USA, we caught up with Prof. Farias who shared his view on the findings of the study and their wider implications. As part of our campaign to recruit patient no. 1000, Prof. Farias received free registration to attend the American Association for the Study of Liver Diseases (AASLD) annual meeting, The Liver Meeting® (TLM 2023). We took this opportunity to ask him about his insights from the conference and emerging topics in the field of hepatology.

November 13, 2023 The 6th CHANCE Investigator Meeting sets the stage for a second phase in the project Members of the CHANCE Executive Group and Management Team presented an update on project progress and discussed next steps on the completion of patient recruitment to ensuring data integrity.

The 6th CHANCE Investigator Meeting took place on 10 November 2023 in Boston, MA, USA, on the occasion of The Liver Meeting 2023 – the annual meeting of the American Association for the Study of Liver Diseases (AASLD).

October 25, 2023 People with cirrhosis and who receive a liver transplant are more susceptible to COVID-19 breakthrough infection Study finds 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 identifies predictive factors associated with breakthrough infection.

BARCELONA—Inadequate supply and lower acceptance rate of COVID-19 vaccines among the adult population remains a matter of concern, particularly in high-risk groups such as patients with chronic liver disease and liver transplant recipients. In people receiving a liver transplant, reduced antibody response to COVID-19 vaccination is known to be associated with the use of immunosupressants and older age. The variable response to COVID-19 vaccines in people with cirrhosis has largely prevented the identification of factors associated with risk and severity of breakthrough infection in this group. The COBALT study – COVID-19 vaccination and biomarkers in cirrhosis and post-liver transplantation – coordinated and sponsored by the European Foundation for the Study of Chronic Liver Failure (EF CLIF) with the support of the Foundation for Liver Research, the European Liver and Intestine Transplant Association (ELITA), the European Liver Patients' Association (ELPA), and the European Association for the Study of the Liver (EASL) aimed to determine the degree of protection conferred by COVID-19 vaccines in people with chronic liver disease and post-liver transplantation. The study published in Hepatology Communications provides evidence of the heterogenous response of COVID-19 vaccine primary series and identifies factors predicting poor vaccine response and risk of breakthrough infection in people with cirrhosis, patients with autoimmune liver disease without cirrhosis, and who have undergone liver transplantation compared to healthy individuals with no previous COVID-19 infection episode and no infection with human immunodeficiency virus.

October 20, 2023 The 5th DECISION General Assembly highlights the commitment and collaborative effort of all partners in the Consortium Members of the DECISION Consortium meet in Padova, Italy, to discuss recent research results in preparation of several manuscripts shedding some new light on the pathophysiology of acute decompensation of cirrhosis and development of acute-on-chronic liver failure (ACLF) – a syndrome associated with high short-term mortality. After three years of intensive work, the upcoming COMBAT trial will use newly identified biomarkers to predict disease progression and test safety and effectiveness of a combinatorial drug therapy.

PADOVA—The DECISION General Assembly was held on 18–20 October 2023 and run in a hybrid format from Padova, Italy. This annual meeting is meant to bring together members of partner institutions to review project progress and help researchers to put their results into perspective, sharing their findings contributes to add clarity to the studies carried out within the project and set the direction to achieve expected project outcomes.

October 16, 2023 EF CLIF researchers among the most cited scientists in the world Six researchers affiliated to EF CLIF are listed in the world’s top 2% highly cited scientists ranking, a science-wide database of 100,000 top scientists that includes 22 scientific fields and 176 subfields.

BARCELONA— The Ranking of the World Scientists: World's Top 2% was created by a group of experts led by John P.A. Ioannidis (Stanford University), Jeroen Baas (Elsevier B.V.) and Kevin W. Boyack (SciTech Strategies). The database is publicly available in the Elsevier Data Repository and regularly updated providing information on career-long and single most recent year impact.

October 10, 2023 CHANCE celebrates the recruitment of its 1000th patient Significant milestone in the first global prospective study analyzing intention-to-treat survival benefit of liver transplantation for patients with severe acute-on-chronic liver failure (ACLF) – a syndrome characterized by acute decompensation of cirrhosis associated with multisystem organ failure and high short-term mortality.

BARCELONA—The CHANCE Management Team announces the recruitment of patient no. 1000. This new milestone means that the study will progress to a data cleaning stage and primary endpoints will be analyzed. The CHANCE study aims to describe the clinical trajectories of patients with acute decompensation of cirrhosis and ACLF in the liver transplant waiting list, and is expected to contribute to issue new guidelines for organ allocation as there are currently no specific priority criteria for patients with ACLF.

October 06, 2023 Three new centers elected members of the EASL-CLIF Consortium: Meet the center coordinators and their teams The EASL-CLIF Consortium Steering Committee met on 22 June 2023 in Vienna, Austria, on the occasion of the EASL Congress 2023, to evaluate new applications by candidate centers as we look to continue increasing our network of university hospitals and tertiary care centers across Europe.

Here, newly elected center coordinators Beti Todorovska, MD, PhD for University Clinic of Gastroenterohepatology (Macedonia), Genco Gençdal, MD for Koç University Hospital (Turkey) and Maria Pilar Ballester, MD, PhD for Hospital Clínico Universitario de Valencia (Spain), tell us about their motivations for joining the EASL-CLIF Consortium.

October 04, 2023 The CHANCE Steering Committee meets online to review preliminary data and the status of patient recruitment As the CHANCE study is approaching the 1000th patient milestone, members of the CHANCE Steering Committee and Management Team met online to review preliminary data and discuss about the state of play with regard to patient recruitment.

BARCELONA—The CHANCE Steering Committee Meeting was held online on 3 October 2023 to review the in-depth patient follow-up assessment carried out by EF CLIF Data Managers and Statisticians over the last few months and to foster discussion around the available data against the primary and secondary endpoints of the study.

September 28, 2023 The 3rd A-TANGO General Assembly sets up the upcoming clinical trial for success Members of the A-TANGO Consortium met online to discuss progress and ways to overcome major challenges in a clinical trial that will test safety of a combinatorial drug therapy in patients with chronic liver disease.

BARCELONA—The 3rd A-TANGO General Assembly took place online on 26 September 2023. The objective of these annual meetings is to share progress made throughout the year among members of the Consortium and create a better understanding of potential risks and limitations of the project. These meetings offer an opportunity to receive feedback from members of the Scientific and Ethical Advisory Board, Data and Safety Monitoring Committee and Impact Board, and make adjustments to ongoing and future activities based on their expert advice.

September 21, 2023 Celebrating 10 years of CANONIC: Challenging traditional practices We caught up with Dr. Laure Elkrief at EASL Congress 2023 to discuss how results from the CANONIC study have changed the field of hepatology and participating in this large-scale study has impacted her career.

Dr. Laure Elkrief is Hepatologist and Assistant Professor at Tours University Hospitals, France, were she is currently carriyng out research on portal hypertension both in cirrhosis and vascular liver disease.

September 20, 2023 Scientific Advisory Board members meet in Barcelona to evaluate EF CLIF's research activities over FY 2022 The annual Scientific Advisory Board Meeting took place on 19 September 2023 at the EF CLIF Headquarters in Barcelona, Spain. Members of the Executive Scientific Committee together with the Coordinating Investigators of the three EU-funded projects MICROB-PREDICT, DECISION and A-TANGO presented an overview of the research outputs over the last year and discussed progress of ongoing projects.

BARCELONA—The Scientific Advisory Board (SAB) is made up of internationally recognized researchers and clinicians with broad expertise in liver disease research. Officially established in 2022, the SAB provides advise about the EF CLIF research programs and overall strategy.

August 30, 2023 Don't miss the ELITA–EF CLIF Monothematic Conference on ACLF, Alcohol and Liver Transplant On the occasion of the 30th Anniversary of the European Liver and Intestine Transplant Association (ELITA), EF CLIF joins efforts with this section of the European Society for Organ Transplantation (ESOT), to bring together experts in acute-on-chronic liver failure (ACLF) and liver transplantation to discuss current practices and the future of the field in Europe.

The purpose of the Monothematic Conference is to provide up-to-date scientific evidence on the role of liver transplantation in patients with acute-on-chronic liver failure (ACLF) or in active drinkers who are in urgent need of a liver transplant. More specifically, the two morning sessions will be dedicated to the diagnosis of ACLF and to the crucial issue of access to liver transplantation for patients with severe ACLF across Europe. The afternoon sessions will focus on the current treatment of alcoholic hepatitis and the place of liver transplantation in active drinkers. For both topics there will be round table discussion based on clinical cases.

August 29, 2023 Behind CHANCE: Staying on top of patient recruitment Patricia Momoyo Zitelli is a member of the team that recruited the 500th patient in the CHANCE study, and won a free registration to attend the EASL Congress 2023. At our 5th CHANCE Investigator Meeting, we took the opportunity to catch up with her to learn more about her role and her highlights of the congress.

After graduating from the school of nursing in 2013, Patricia started at Hospital das Clínicas da Universidade de São Paulo in Brazil as a registered nurse. Over the years, she has gained a wealth of knowledge and expertise, and has actively participated in the coordination of complex and large-scale clinical studies.

July 12, 2023 Celebrating 10 years of CANONIC: Enabling better clinical management of patients with ACLF To celebrate the 10th aniversary of the publication of results from the CANONIC study that allowed for the definition of the syndrome we refer to as "acute-on-chronic liver failure" (ACLF), we took the opportunity to catch up with Dr. Minneke Coenraad at the EASL Congress 2023 to discuss her views on the past, present and future of hepatology.

Dr. Minneke Coenraad is Gastroenterologist and Hepatologist at Leiden University Medical Center, The Netherlands. Her research covers a wide breadth of areas including hepatocellular carcinomas, complications of cirrhosis and liver transplantation.

June 23, 2023 CHANCE investigators meet on the occasion of the EASL Congress 2023 in Vienna, Austria The 5th CHANCE Investigator Meeting took place on 22 June 2023 in Vienna, Austria

VIENNA—On the occasion of the EASL Congress 2023, the 5th CHANCE Investigator Meeting brought together investigators, research nurses, data managers, statisticians and bioinformaticians to review and discuss project progress and address key issues regarding the completion of patient records.

June 02, 2023 New hemodialysis machine proves safe and effective for treatment of acute-on-chronic liver failure The first-in-human clinical trial of DIALIVE, a liver dialysis device, meets safety requirements and shows improvement of pathophysiological markers of chronic liver disease reducing time to resolution of acute-on-chronic liver failure compared to standard of care.

BARCELONA—Acute-on-chronic liver failure (ACLF) is a syndrome associated with severe systemic inflammation, multiorgan system failure and high short-term mortality. Liver transplantation is the only one treatment option for patients with ACLF able to restore essential functions of the liver where no alternative treatment of comparable effectiveness exists. DIALIVE, a new liver dialysis device, demonstrated its potential as a disease-modifying therapy and improved markers underlying the physiopathology of ACLF. Results from the first-in-human clinical trial of DIALIVE were published ahead of print in

May 30, 2023 Differences in percentage of Native American ancestry are associated with the odds to develop severe acute-on-chronic liver failure and risk of short-term mortality in the Latin American population A large prospective observational study carried out in Latin America finds high prevalence of severe acute-on-chronic liver failure and high risk of 28-day mortality in patients hospitalized for acute decompensation of cirrhosis with a higher percentage of Native American ancestry (and reported race) than that of European and African descent.

BARCELONA—The basis of genetic ancestry (and race) underlying differences in disease occurrence, outcomes or response to treatment remains unclear and most often racial and ethnic diversity is underrepresented in clinical research contributing to further expand the gap of health inequities. According to the Global Burden of Disease 2010 study, complications of cirrhosis accounted for 1 million deaths worldwide and caused 31 million disability adjusted life years (DALYs) that year. Noteworthy, liver cirrhosis mortality in Mexico was the highest in Latin America in 2010 with a mortality rate of 38.3 per 100,000. Patients with acute decompensation of cirrhosis suddenly develop ascites, hepatic encephalopathy, gastrointestinal hemorrhage, or any combination thereof. The CANONIC study, the first large, observational study carried out in Europe by the European Association for the Study of the Liver-Chronic Liver Failure (EASL-CLIF) Consortium, identified acute-on-chronic liver failure (ACLF) as a distinct syndrome that develops in 30% of patients with acute decompensation of cirrhosis, and is characterized by acute systemic inflammation, multi-system organ failure, and a high risk of death within 28 days after hospital admission. The ACLARA study – Prevalence, epidemiology, characterization and mechanism of ACLF in Latin America – sheds new light on the potential impact of genetic ancestry and reported race on the severity of ACLF and risk of short-term mortality. The study carried out in 1274 patients non-electively hospitalized for acute decompensation of cirrhosis in 44 university hospitals from 27 cities in 7 Latin American countries (Argentina, Brazil, Chile, Colombia, Mexico, Paraguay, and Peru), highlights the importance of including genetic ancestry (and race) in liver disease research and clinical practice for being variables that capture relevant epidemiological information. Findings from this study, published ahead of print in Gastroenterology, show that social factors (i.e., admission to public hospitals compared to private hospitals) and markers of organ function independently correlate with higher short-term mortality. The data also suggest an association between increased percentage of Native American ancestry (and reported race) and development of ACLF independent of alcohol-related hepatitis and bacterial infections, two major precipitant events of acute decompensation of cirrhosis and progression to ACLF.

May 16, 2023 A CHANCE for researchers to win a registration for The Liver Meeting 2023 We call all investigators in CHANCE to help us reach the 1000th patient milestone

The CHANCE study aims to recruit 2000 patients by the end of 2023. With 58 actively recruiting centers in 20 countries across the world, we are confident that CHANCE will render positive results and provide answers to our primary objective: To compare 1-year graft and patient survival rates after liver transplantation in patients with acute-on-chronic liver failure (ACLF) grade 2 or 3 at the time of liver transplantation with patients with decompensated cirrhosis without ACLF and transplant-free survival of patients with ACLF grade 2 or 3 not listed for liver transplantation.

May 05, 2023 CHANCE investigators meet on the occasion of ILTS 2023 in Rotterdam, The Netherlands Having reached a mid-point in the CHANCE study, the 4th CHANCE Investigator Meeting reunited investigators across participating centers to discuss about project progress on 4 May 2023 in Rotterdam, The Netherlands.

ROTTERDAM—The 4th CHANCE Investigator Meeting took place in Rotterdam, The Netherlands on the occasion of the 2023 International Congress of ILTS, ELITA and LICAGE (ILTS 2023). The CHANCE investigator meeting brought together 35 investigators and professionals from 12 countries (Argentina, Austria, Canada, France, Germany, India, Italy, Japan, Spain, The Netherlands, UK, and USA), 22 people attended in person and 13 joined online, to review and discuss project progress and address challenges of patient recruitment and data collection.

February 23, 2023 Celebrating 10 years of CANONIC: It's all about improving care and survival for patients with ACLF To celebrate 10 years since the publication of results from the CANONIC study, we talked with Prof. Richard Moreau, leading researcher in this prospective observational investigation, about the impact of chronic liver disease, approaches to treatment, and best practices.

The CANONIC study – 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. Results from the CANONIC study opened up a new venue of liver disease research that will continue expanding in the following years.

February 20, 2023 Study identifies three prognostic metabolites that could be used to improve care for patients with chronic liver disease Two new prognostic models based on three metabolites reflecting systemic inflammation, mitochondrial dysfunction and sympathetic nervous system activation are found to better predict short-term mortality in acute decompensation of cirrhosis and acute-on-chronic liver failure (ACLF).

BARCELONA—Systemic inflammation is the major driver of acute decompensation of cirrhosis contributing to the development and severity of acute-on-chronic liver failure (ACLF) – a syndrome associated with multiorgan failure and high short-term mortality. About 20% of patients with acute decompensation of cirrhosis develop ACLF within three months of hospitalization. The model for end-stage liver disease (MELD) has been widely used to predict mortality in patients with acute decompensation of cirrhosis and to prioritize patients for liver transplantation. However, MELD and its variations fail to predict early deaths in ACLF patients. The Chronic Liver Failure Consortium acute-on-chronic liver failure (CLIF-C ACLF) score has proven to be superior, yet has limitations in predicting short-term mortality in a significant number of patients. In a previous study, researchers at EF CLIF showed that the presence of a set of metabolites – small molecules that function as intermediate or end products of metabolic reactions that occur throughout the body – correlated with severity of systemic inflammation and ACLF.

February 17, 2023 International Day of Women and Girls in Science: Debbie Shawcross Meet Debbie Shawcross, MD, PhD, Professor of Hepatology and Chronic Liver Failure at King's College London and King's College Hospital NHS Foundation Trust, UK, and member of our Inspiring and Writing Group.