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.

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.

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.

BARCELONA—Metabolic-associated fatty liver disease (MAFLD) is a condition caused by accumulation of extra fat in the liver that can result in severe liver injury. A new study in mice highlights 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 fatty liver disease. The study, published on 1 April 2023 in Hepatology, provides the mechanistic basis by which transgenic fat-1 mice, which carry an enzyme that endogenously replaces membrane omega-6-polyunsaturated PUFAs by omega-3 PUFAs, become resistant to liver disease and likely other inflammatory diseases characterized by mitochondrial dysfunction.

BARCELONA—Mitochondria are the primary source of reactive oxygen species contributing to the activation of an inflammatory response in a wide range of pathophysiological conditions such as liver cirrhosis. In patients with decompensated cirrhosis serum albumin levels are low, and albumin is usually given to these patients to prevent and treat several complications of cirrhosis. Albumin is synthesized in the liver and is the most abundant protein in the bloodstream contributing to plasma oncotic pressure by retaining water into the intravascular space. Albumin binds and moves many small molecules through the blood, including certain drugs. It plays an important role as a modulator of the immune response to pathogens and exerts a protective effect on hepatocytes against the pro-inflammatory cytokine tumor necrosis factor alpha (TNFα) as reported in a previous study. In this study, researchers of the European Network for Translational Research (ENTR) from EF CLIF, Hospital Clínic de Barcelona-Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), and Grifols explored the role of albumin in maintaining mitochondrial homeostasis during inflammation in a series of experiments using a mouse model of TNFα-induced liver injury, liver slice cultures and isolated hepatocytes from wild-type mice. The study first published on 21 February 2023 in FASEB Journal provides new insights into the mechanism by which albumin may protect hepatocytes from excessive oxidative stress, contribute to the homeostatic control of mitochondrial metabolism and support normal function of the liver.

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.

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.

In celebration of International Day of Women and Girls in Science, we want to raise awareness of the work of women in hepatology and inspire the next generation of budding scientists.

In celebration of International Day of Women and Girls in Science, we want to raise awareness of the work of women in hepatology and inspire the next generation of budding scientists.

In celebration of International Day of Women and Girls in Science, we want to raise awareness of the work of women in hepatology and inspire the next generation of budding scientists.

In celebration of International Day of Women and Girls in Science, we want to raise awareness of the work of women in hepatology and inspire the next generation of budding scientists.

In celebration of International Day of Women and Girls in Science, we want to raise awareness of the work of women in hepatology and inspire the next generation of budding scientists.

In celebration of International Day of Women and Girls in Science, we want to raise awareness of the work of women in hepatology and inspire the next generation of budding scientists.

In celebration of International Day of Women and Girls in Science, Ingrid gives insights into her work and shares her hopes and research goals as a scientist.

In celebration of International Day of Women and Girls in Science, we want to raise awareness of the work of women in hepatology and inspire the next generation of budding scientists.

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.

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.