EASL Congress 2024, taking place in Milan and online and convened annually by the European Association for the Study of the Liver, showcased new research that promises to transform the landscape of liver disease treatment. Some 7,000 scientists, doctors, public health officials, industry representatives and affected communities are attending the event which runs through until Saturday, 8 June. From innovative microbiota transplants to new drugs and intelligent testing platforms, these studies highlight significant advancements in the fight against liver diseases.

Prof. Aleksander Krag, EASL Secretary General stated, “The research presented at this year’s congress exemplifies our commitment to advancing liver disease treatment. We are witnessing a new era of innovation that will bring tangible benefits to patients globally.”

Prof. Debbie Shawcross, EASL Vice-Secretary added, “These studies are not just scientific milestones; they represent real hope for millions of people suffering from liver diseases worldwide. The collaborative efforts seen at EASL Congress 2024 underline the importance of united action in tackling these complex health challenges.” 

New hope for Hepatic Encephalopathy patients through fecal microbiota transplant

Liver cirrhosis is increasing worldwide, and a disabling brain complication of cirrhosis is hepatic encephalopathy (HE). HE is associated with harmful gut microbes, which are targets of conventional therapies. However, despite these therapies, HE can recur with serious consequences. A study led by Dr. Jasmohan Bajaj from Virginia Commonwealth University, aiming to break this vicious cycle has demonstrated that fecal microbiota transplant (FMT) significantly reduces the recurrence of hepatic encephalopathy (HE) in cirrhosis patients. The trial, involving 60 patients, showed that FMT, whether administered via oral capsules or enemas, was effective and safe, with HE recurrence dropping from 40% in the placebo group to 9% in the FMT group. 

"It is possible to further benefit the microbiome to improve brain function in liver disease using healthy donor bacteria. Harmful recurrences of disabling hepatic encephalopathy can be prevented by microbiota transplant independent of doses, route of administration, or whether the healthy donor is vegan or omnivorous," said Dr. Bajaj, Professor at the School of Medicine Internal Medicine Virginia Commonwealth University.

Phase 2 Dose-Ranging Randomised Clinical Trial of Capsular or Enema Fecal Microbiota Transplant to Prevent Hepatic Encephalopathy in Cirrhosis Already on Rifaximin and Lactulose (GS-001)
Session: General Session I, Thursday 6 June 10:30 – 10:45 CEST

Breaking new ground in MASLD treatment

Dr. Jörn M. Schattenberg and his team at the University Medical Center of the Johannes Gutenberg University, Mainz, Germany, have reported promising results from their phase 2a study on ZED1227, a transglutaminase 2 inhibitor, for treating Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) with significant fibrosis.

Key findings show a significant reduction in Procollagen-C3 (PRO-C3) levels and a decrease in PRO-C6, a biomarker linked to cardiovascular disease, in patients with high disease activity. ZED1227 was well tolerated, with no serious adverse events related to the medication.

Although the primary endpoint was not met, ZED1227 shows potential as a valuable treatment option for patients with high disease activity, addressing a significant unmet need.

“Transglutaminase 2 inhibitor ZED1227 shows anti-fibrotic effects in a subgroup of MASLD patients with significant fibrosis,” said Dr Schattenberg, Director of Metabolic Liver Research Program, Department of Medicine, University Medical Center of the Johannes Gutenberg University, Mainz, Germany.

Phase 2a Randomised Trial with the Transglutaminase 2 Inhibitor ZED1227 in Patients with MASLD (OS-115)
Session: Abstract session: MASLD: Therapy, Saturday, 8 June 11:00 CEST

Revolutionising liver disease diagnosis with intelligent testing

Chronic liver disease (CLD) is a serious and potentially fatal global health problem and in early stages it may be symptomless but preventable. Pre-existing lab tests can detect CLD but are complex and follow-up test results can be difficult for non-liver specialist to interpret. The intelligent Liver Function Testing (iLFT) platform, implemented in 2018 in NHS Tayside primary care uses an algorithm programmed into the laboratory computer system, automatically combining patient information with initial lab test results, performing additional testing where needed and interpreting results - providing advice on likely cause and stage of CLD. Over five years, iLFT significantly improved CLD diagnosis and management, performing over 26,000 tests and providing crucial insights into disease etiology and stage. The platform proved adaptable, incorporating new clinical guidelines and reducing unnecessary specialist referrals.

“At EASL Congress 2024, I am delighted to share the 5-year results from our innovative, intelligent Liver Function Testing platform, showing the impact it has on reducing advanced CLD and saving lives by doing simple things smarter and more efficiently,” said Dr. Damien Leith, University of Dundee, Scotland, United Kingdom. 

Intelligent Liver Function Test 5 Years On – The Evolution of an Intelligent Platform (OS-007-YI)
Session: Abstract session – Alcohol-related liver disease, Thursday, 6 June, 17:30 – 17:45 CEST

Changing the paradigm for liver transplantation in severe ACLF

Acute-on-Chronic Liver Failure (ACLF) often follows acute decompensation of cirrhosis and leads to devastating short-term outcomes. Despite supportive management, there are no effective evidence-based therapies available. Salvage liver transplantation improves survival but is controversial due to unknown risks. Current organ allocation systems, based on MELD scores, fail to account for extrahepatic organ failure risks.

Interim results from the global CHANCE study, led by Dr. Thierry Gustot of Hôpital Erasme, Université Libre de Bruxelles, were presented, involving 824 patients from 62 centers across four continents. The study found that liver transplantation for severe ACLF patients resulted in an impressive 3-month survival rate of 88%, compared to 15% for those denied liver transplantation. These findings highlight the high mortality rate for severe ACLF patients on the waiting list and the inadequacy of MELD-Na in predicting these events, underscoring the urgent need for organ allocation system reform.

“Outstanding outcomes after liver transplantation for selected patients with severe Acute-on-Chronic Liver Failure demonstrate the need for changes in organ allocation to save more lives,” said Dr. Gustot.

Excess Waitlist Mortality and Survival Benefit of Liver Transplantation for Patients with Severe Acute-on-Chronic Liver Failure: Interim Results of the CHANCE Study (LBO-004)
Session: Late-breaker, Saturday, 8 June, 15:00 CEST 

Innovative treatment for sarcopenia and Hepatic Encephalopathy

Muscle loss, or sarcopenia, is a significant issue for liver cirrhosis patients, burdening both individuals and the healthcare system. Currently, there are no approved treatments for sarcopenia, highlighting a major unmet need. LPCN 1148, an investigational oral treatment, has demonstrated remarkable efficacy in increasing muscle mass and reducing hepatic encephalopathy (HE) episodes in men with cirrhosis. The trial results, presented by Dr. Arun J. Sanyal, showed sustained benefits over a year, suggesting LPCN 1148 as a safe, patient-friendly option to enhance quality of life, reduce hospitalisations, and lessen caregiver burden. The positive results pave the way for further testing in other areas, including in women, pre-transplant strengthening, post-transplant recovery, and other severe conditions characterised by muscle loss.

“I am delighted to see the durability of the results noted in this important trial to improve sarcopenia in a very sick population of patients with decompensated cirrhosis. These provide a strong rationale for further studies on the overall benefits and risks of LPCN 1148 in this population,” commented Dr. Sanyal, Stravitz-Sanyal Institute for Liver Disease and Metabolic Health, Virginia Commonwealth University, Richmond, United States

“The rapid and sustained increases in muscle mass seen in this study with LPCN 1148 are very exciting, especially as there are currently no FDA-approved pharmacotherapeutics for sarcopenia in cirrhosis,” added Dr. Jennifer Lai, Division of Gastroenterology and Hepatology, University of California San Francisco, San Francisco, United States. 

Intervention with Oral LPCN 1148 Improves Sarcopenia and Hepatic Encephalopathy (HE) in Patients with Cirrhosis: A 52-Week Phase 2 Randomised Clinical Trial (LBO-005)
Session: Late-breaker, Saturday 8 June, 15:00 – 15:15 CEST 

This news release was publishedby the European Association for the Study of the Liver on May 5, 2024.