State-of-the-Art lectures at EASL Congress 2024

Our specially curated State-of-the-Art lectures featured key opinion leaders and authorities from various fields, and offered insights into the latest cutting-edge developments that are shaping the future of hepatology.

Understanding the molecular basis of genetic variations conferring susceptibility and resistance to steatotic liver disease.

Helen H. Hobbs, University of Texas Southwestern Medical Center, US

Helen H. Hobbs is an Investigator of the Howard Hughes Medical Institute at the University of Texas Southwestern Medical Center (UTSW) in Dallas Texas. After graduating from Stanford University and Case Western Reserve Medical School, she trained in internal medicine and endocrinology at Columbia-Presbyterian and UTSW. She joined the UTSW faculty in 1987 where she is Professor of Internal Medicine and Molecular Genetics and Director of the McDermott Center for Human Growth and Development. Together with Jonathan Cohen, she has used human genetics to identify sequence variations of large effect sizes on levels of plasma LDL-cholesterol (ABCG5/ABCG8, LDLRAP, PCSK9, NPC1L1, ANGPTL3) and triglyceride (ANGPTL3,-4,-8). More recently, she discovered the two most impactful genetic risk factors for fatty liver disease (PNPLA3, TM6SF2). Gene identification is the starting point for studies that have elucidated pathways and processes altered by the defective genes she has identified. She is a member of the National Academy of Medicine, the American Academy of Arts and Sciences, and the National Academy of Sciences. She is recipient of The Breakthrough Prize in Life Sciences and the Harrington Prize for Innovation in Medicine. 

About this session

We identified the two genetic risk variants of greatest effect on steatotic liver disease (SLD), ranging from steatosis to cirrhosis and HCC. The first, PNPLA3(148M), explains ~60% of the racial differences in prevalence of SLD (Hispanics>Whites>Blacks). Despite being the most impactful genetic risk factor for two forms of liver disease (MASLD and alcohol-related), its pathogenic link to liver disease and its physiological role in liver health remain poorly defined. Here I will review our recent studies of the relationship between PNPLA3 function, triglyceride homeostasis, and SLD. The second risk variant, TM6SF2(167K), is in a gene of unknown function that is involved in a completely different pathway. Elucidation of the molecular basis for the links between these two genetic variants and SLD has informed not only the pathogenesis of SLD, but its relationship to cardiometabolic disorders.    

Learning objectives

  • Appreciate the power of genetics to sever the Gordian knot of association in common, complex diseases.
  • Review the cause of SLD due to genetic variations in PNPLA3 and TM6SF2.
  • Discuss the role of lipid accumulation in the pathogenesis of the full spectrum of SLD.
  • Explore how genetics can inform the relationship between SLD and other disorders, including metabolic dysfunction and cardiovascular disease.

Anticoagulation in patients with cirrhosis

Lara Roberts, King’s College Hospital, UK 

Dr Lara Roberts is a Consultant Haematologist at King’s College Hospital, Honorary Reader in Thrombosis and Haemostasis at King’s College London and MRC Clinical Academic Research Partnership Fellow. Dr Roberts is the clinical lead for venous thromboembolism at KCH. She is the NIHR haematology lead for the South London and a member of the BSH Haemostasis and Thrombosis taskforce. Dr Roberts is co-chair for the ISTH SSC on Haemostatic management of patients with Liver Disease. Her current research focuses on investigating haemostasis in acutely ill patients with advanced chronic liver disease.  

About this session

Dr Roberts will discuss the role of anticoagulation in patients with cirrhosis, focussing on the prevention and treatment of deep vein thrombosis, pulmonary embolism and prevention of stroke in atrial fibrillation. She will discuss the advantages and disadvantages of the available agents including direct oral anticoagulants, along with specific considerations in patients with progressing liver disease and during acute illness. The impact of anticoagulation on patient survival will be reviewed, along with future directions in this domain.

Learning objectives

  • To be able to select the appropriate anticoagulant to prevent/treat deep vein thrombosis, pulmonary embolism and for stroke prevention in atrial fibrillation for patients with cirrhosis
  • To understand the key considerations for safely managing anticoagulation in patients with cirrhosis during episodes of acute illness or with disease progression
  • To be aware of emerging research regarding the role of anticoagulation in managing patients with cirrhosis and of future anticoagulant agents in development

Hepatic encephalopathy

Dominique Thabut, Sorbonne Université, France

Pr Dominique Thabut is full Professor in Hepatology in Pitié-Salpêtrière hospital, Sorbonne Université, Paris, France. She is Head of the Department of Hepatogastroenterology. Her field of interest has always been the management of patients with end-stage liver diseases. Her group is running a liver intensive care unit and an outpatient clinic dedicated to patients with hepatic encephalopathy. She is President Elected of ISHEN (International Society of Hepatic Encephalopathy and Nitrogen Metabolism) and member of the Baveno Cooperation Research group. Her current research focuses on characterization of neurocognitive disorders in patients with chronic liver diseases and portal hypertension/TIPS in decompensated cirrhotic patients.

About this session

Hepatic encephalopathy is a dreadful complication of cirrhosis. Its diagnosis is not as easy as it could appear at first sight, either in its overt or in its minimal form, because of differential or associated diagnosis. Treatments are available but do not completely reverse symptoms in a large proportion of patients, and new therapeutic tracks are eagerly awaited. In special populations, like patients indicated for TIPS or liver transplantation, hepatic encephalopathy assessment is mandatory to take the right therapeutic decision and offer the best management to patients. This presentation will help understanding how to handle cirrhotic patients at risk or with hepatic encephalopathy, and look at future directions for their management.

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