State-of-the-art lectures
The State-of-the-Art lectures at EASL Congress 2025 feature key opinion leaders and authorities from various fields, and offer insights into the latest developments that are shaping the future of hepatology.
Jean-Pierre Benhamou Clinical State of the Art Lecture
The promise and pitfalls of non-invasive testing
Friday, 9 May, 14:00 – 14:45 CET
Annalisa Berzigotti graduated in Medicine and specialised in Internal Medicine, then earned a doctorate in Ultrasound in Medicine at the University of Bologna, Italy, and later a doctorate in Hepatology at the University of Barcelona, Spain (where she worked as a clinical researcher from 2008 to 2014). In December 2014, she joined the Hepatology Group at the Department of Visceral Surgery and Medicine, Inselspital, University Hospital of Berne, Switzerland. Since 2023, she has been Full Professor of Clinical Hepatology at the University of Berne, as well as Chief of Hepatology and Co-Director of the Department of Visceral Surgery and Medicine at Inselspital.
Her research focuses on the clinical and diagnostic aspects of chronic liver disease, particularly non-invasive assessment of cirrhosis and portal hypertension, and she has authored over 300 peer-reviewed articles. Notable contributions include optimising ultrasound and elastography techniques, identifying obesity as an independent risk factor for decompensation, and showing that intensive lifestyle intervention effectively treats portal hypertension in obese cirrhotic patients.
Dr. Berzigotti served on the EASL Governing Board Scientific Committee (2016–2019), and she currently sits on the Governing Board of the Swiss Association for the Study of the Liver (SASL), is Vice-Chair of the Baveno Cooperation, Liver Representative at the United European Gastroenterology Council, member of the Steering Committee of the second EASL–Lancet Commission, and Co-Editor of the Journal of Hepatology. She was the first recipient of the Stern-Gattiker Prize of the Swiss Academy of Medical Sciences (2018) and the first woman to receive the Lucie Bolte Prize (2021).
About this lecture
Non-invasive testing (imaging methods, elastography, and blood biomarkers; NITs) has transformed liver disease management over recent decades, offering a safe, quick, repeatable, and patient-friendly approach to guide treatment decisions across various clinical scenarios. Promises that have been fulfilled by NITs include diagnosing liver steatosis and liver fibrosis, staging of chronic liver disease, and stratifying the risk of liver-related outcomes. Importantly, these tools nowadays enable the diagnosis of advanced fibrosis and portal hypertension in asymptomatic patients with compensated chronic liver disease.
However, several pitfalls and challenges remain. NITs may yield false positive and negative results, misrepresenting fibrosis stage and associated risks. Given that the armamentarium of NITs is broad and constantly increasing, there is need of careful integration of clinical context (e.g. prevalence of the condition of interest in the tested population), disease etiology, and technical expertise for reliable results, which require specific training. Furthermore, the cost-effectiveness of NITs varies depending on their availability and reimbursement policies. Finally, the currently used NITs for fibrosis and portal hypertension are downstream of complex biological processes, and currently lack the granularity needed for precision medicine.
This State of the Art Lecture will provide an updated overview of NITs in liver disease, with focus on their use in compensated advanced chronic liver disease. It will also cover some ongoing developments and novel applications, including their use in the context of fibrosis regression, treatment monitoring, and individualized risk prediction.
Learning objectives
By the end of the lecture, attendees will be able to:
- describe the main role of non-invasive tests (NITs) in managing chronic liver disease
- remind the limitations and challenges of NITs in this field
- have a glimpse into future development and applications of NITs
Karl Wilhelm von Kupffer Basic Science State-of-the-Art:
From Bench to Bedside: Discovery and Development of First-in-class MKK4 Inhibitors to enhance Liver Regeneration and prevent Liver Failure
Thursday, 8 May, 14:00 – 14:45 CET
Lars Zender studied Medicine at Hannover Medical School, earning his M.D. in 2002 and pursuing both clinical and research training in gastroenterology and oncology. After completing a postdoctoral fellowship with Dr. Scott W. Lowe at Cold Spring Harbor Laboratory in the United States, he led an Emmy Noether Research Group at the Helmholtz Centre for Infection Research and Hannover Medical School. He subsequently held positions as Assistant Professor of Experimental Gastrointestinal Oncology and, later, W3 Professor and Head of Gastrointestinal Oncology in Tübingen, Germany.
Since 2019, Dr. Zender has served as Professor of Medical Oncology, Chairman of the Department of Medical Oncology and Pneumology at the University Hospital Tübingen (UKT), and Spokesperson of the iFIT Cluster of Excellence. In 2023, he became Managing Director of the National Center for Tumor Diseases (NCT) Tübingen-SouthWest. An active member of several professional societies, he also reviews for top-tier journals such as Nature, Cell, and Cancer Cell. Dr. Zender has organised international conferences, supervised more than 20 doctoral and postdoctoral researchers, and continues to advance translational cancer research, particularly in the field of liver oncology.
About this lecture
Liver diseases are a major and increasing global health concern, causing over two million deaths annually worldwide. Over the past three decades, the number of deaths due to liver diseases has risen by 50% and is expected to double within the next 20 years. A key problem in acute and chronic liver diseases, as well as after extended liver resections, is the inability of hepatocytes to regenerate sufficiently and maintain a critical functional liver mass. Although healthy livers can regenerate almost indefinitely, damage-associated changes in the hepatic microenvironment of injured livers compromise this regenerative capacity, and the underlying molecular mechanisms remain poorly understood.
The Karl Wilhelm von Kupffer Basic State of the Art Lecture at EASL 2025 will trace the discovery of MKK4 as a therapeutic target for boosting liver regeneration, from its initial identification to the development of first-in-class MKK4 inhibitors, along with their preclinical and phase I testing. MKK4 was initially recognized as a master regulator of hepatocyte regeneration through the first in vivo RNA interference screen. MKK4 is a MAP2 kinase within the stress-activated protein kinase (SAPK)/mitogen-activated protein kinase (MAPK) signaling networks and can be activated by various stress stimuli. Its downstream substrates include JNK1, 2, and 3 (also activated by MKK7), and the p38 MAPK isoforms (chiefly activated by MKK3 and MKK6). Silencing MKK4 via shRNAmir was shown to unleash the liver’s innate regenerative ability—particularly in acutely or chronically injured livers—by rerouting SAPK signaling largely through MKK7 and JNK1, thereby triggering a pro-regenerative transcriptional program mediated by ATF2 and ELK1.
The session will also describe the development and characterisation of first-in-class small-molecule MKK4 inhibitors (MKK4i) in both in vitro and in vivo models, including murine and porcine hepatectomy studies.
Administration of the clinical candidate HRX215 prevented post-hepatectomy liver failure (PHLF) and ensured survival in an 85% hepatectomy pig model, suggesting that enhanced liver regeneration induced by HRX215 could be a promising therapeutic approach for human PHLF and the related small-for-size syndrome after liver transplantation. Testing of HRX215 in 48 healthy volunteers (EudraCT 2021-000193-28) demonstrated favorable safety and pharmacokinetic profiles. Upcoming clinical trials will investigate HRX215 as a novel strategy to prevent or treat liver failure after extensive oncological liver resections or transplantation of small liver grafts.
Learning objectives
- Current treatment options for acute and chronic liver diseases (brief overview).
- Potential of functional genetic screening techniques (shRNAmir, Crispr/CAS9), in particular direct in vivo screens, to pinpoint therapeutic targets in complex biological systems.
- Functional genetic validation of MKK4 as a target to increase liver regeneration in preclinical mouse models.
- Function of stress-activated protein kinase (SAPK)/mitogen-activated protein kinase (MAPK) signaling networks.
- Structure-based development and characterization (NMR-spectroscopy) of first-in- class small molecule inhibitors of the dual specific kinase MKK4 (MKK4i).
- Preclinical characterization of MKK4i increased liver regeneration upon hepatectomy in murine and porcine models.
- Phase I trial results with the clinical candidate HRX215 (safety and pharmacokinetics) in humans.
- Discussion of clinical trial designs to probe HRX215 for prevention/treatment of liver failure after extensive oncological liver resections or after transplantation of small grafts.
State-of-the-art: Can genetics change our way of thinking about unexplained cholestasis?
Wednesday, 7 May, 17:00 – 17:45 CET
Richard Thompson is Professor of Molecular Hepatology at King’s College London, and Honorary Consultant Paediatric Hepatologist at King’s College Hospital, London.
His group identified several of the genes that cause PFIC. These have led to a better understanding of the pathophysiology and natural history the diseases. He has gone on to lead several clinical trials in the treatment of cholestatic liver disease.
In recent years it has become clear that the genes involved in early onset paediatric disease are also important in the aetiology of adult onset disease, and Richard has been at the forefront of exploring their true role. He is the clinical lead for the Liver Molecular Genetics laboratory that provides NGS-based testing for liver, gastrointestinal and pancreatic disease for most of the UK. He is a member of the NIDDK-funded ChiLDReN network, and on the steering committees of GALA and NAPPED consortia.
About this lecture
This state-of-the-art lecture will explore how emerging insights into genetic factors can reshape our approach to unexplained cholestasis. Attendees will gain an understanding of the mechanisms involved in genetic cholestasis, learn how certain genetic variations may play a role in late-onset disease, and discover criteria for determining when genetic testing is appropriate. In addition, the session will offer guidance on interpreting test results and integrating this knowledge into clinical decision-making.
Learning objectives
- To understand the mechanisms involved in genetic cholestasis
- To understand something of role of genetic variation in late onset disease
- To learn when to send genetic testing
- To know how to understand the results
