about

GENIAL is funded by the European Union under number 101096312

The consortium brings together partners with unique expertise in clinical hepatology, as well as artificial intelligence to improve diagnosis of ALD-HC

The identification of environmental factors and genetic variations promoting alcohol-related hepatocellular carcinoma (ALD-HCC) will enable the development of targets and associated models enabling early-stage detection of individuals at risk of developing alcohol-related liver cancer thus improving drastically curative options and prognosis for patients.

6,2%

6.2% of all deaths in Europe are related to alcohol consumption*

*according to the Global Burden of Disease (GBD) modelling.

90%

is the proportion of Hepatocellular carcinoma (HCC) in the total of liver cancers

40%

of premature liver-related deaths in Europe every year

6,2%

6.2% of all deaths in Europe are related to alcohol consumption*

*according to the Global Burden of Disease (GBD) modelling.

90%

is the proportion of Hepatocellular carcinoma (HCC) in the total of liver cancers

40%

of premature liver-related deaths in Europe every year

objectives

01 to uncover

genetic variants influencing ALD-HCC risk

02 to investigate

gene-environment interactions at single-cell level in ALD-HCC

03 to characterize

ALD-HCC related environmental factors at population level

04 to develop

AI models using large prospective cohorts for improved ALD-HCC risk prediction

05 to communicate

results to all EU citizens, including researchers, patients and the general public

team

Eric TREPO
Coordinator

Eric TREPO

Coordinator

Hepatology specialist at Université Libre de Bruxelles

« It is with great pleasure that I introduce you to an extraordinary initiative set to redefine the landscape of alcohol-related liver cancer (ALD-HCC) in Europe »

Eric TREPO
Coordinator

WP1 Introduction by Jessica ZUCMAN ROSSI, WP1 Leader

Director of INSERM Research Unit

Identification of novel inherited genetic variants predisposing to ALD-HCC

We will identify in WP1 common and rare genetic variant mudulating the risk of ALD-HCC. We will evaluate those variants in the general population as well as NAFLD cohorts.

Our main objective is to identify novel inherited genetic variants predisposing to ALD-HCC. Those variants will be assesseld for gene-environment interactions at molecular levels in WP2 and help define risk stratification in WP3.

Eric TREPO
Coordinator

WP2 Introduction

VIB-KU LEUVEN CENTER FOR CANCER BIOLOGY Laboratory of cellular Metabolism and Metabolic Regulation

Evaluation of gene-environment interactions for the risk of ALD-HCC development at molecular level

WP2 will evaluate how inherited genetic variants of ALD-HCC patients can be influenced by the liver environment. This will allow us to gain better insight into the onset of ALD-HCC and identify potential preventive drug targets. To increase our understanding of gene-environment intercations for the risk of ALD-HCC, we will:

  • 1- Investigate the gene expression profile, nutrient/lipid metabolism and tissue anatomy in (cancerous and non-cancerous) liver tissue of ALD-HCC patients with inherited genetic variations and liver tissue of healthy people using single cell and spatal-omics approaches.
  • 2-  Perform multi-omics data integration for each inherited genetic variant, identified in WP1, to identify the involvement of metabolites/lipids, specific cell types, cellular pathways and specific tissue disorganization.
  • 3- Validate findings in preclinical mouse models

We will use cutting-edge technologies: single cell/nuclei RNAseq, spatial transcriptomics/metabolomics/lipidomics and histological profiling. These will provide us, with unprecedented mechanistic and conceptual detail, information on how gene-environment interactions unfold in alcohol-related liver carcinogenesis.

Eric TREPO
Coordinator

WP3 Introduction

Characterization of gene-environment interactions for the risk of ALD-HCC development at population level

WP3 will use clinical data and available biobanks of more than 4000 European patients with compensated cirrhosis included in four prospective cohorts and one randomized trial dedicated to HCC surveillance.

The overall objective of WP3 is to provide an extensive characterization of clinical, histological and radiological factors and how they interact with inherited genetic variants on the risk of ALD-HCC. WP3 will therefore pursue the following specific objectives.

  • Objective 1:Generation of genetic-based HCC risk scoring systems (GRS)taking into account environmental factors
  • Objective 2: Integrate environmental, genetic and imaging data using AI and machine learning approaches to improve HCC risk stratifaction in ALD and NAFLD.
  • Objective 3:Improve early-stage HCC detection in high-risk patients using liver MRI, radiomics and liquid biopsy

The robust methodology of WP3 encompasses a comprehensive approach combining clinical, genetic, and imaging data with advanced machine learning/AI techniques. This strategy will allow the refinement of HCC risk scoring systems, improve tumour early detection and ultimately trigger personalized surveillance, thereby enhancing patient outcomes and cost-effectiveness.

Eric TREPO
Coordinator

WP4 Introduction by Marko KORENJAK

Dissemination, Training, communication and exploitation

The main objective of this work package is to set up and coordinate efficient strategies for internal and externalcommunication in the GENIAL project, to disseminate information and train relevant stakeholders outside of the project.

Objectives:

  • Identity creation, creation of dissemination infrastructure, external dissemination actions and communication
  • Internal dissemination and its management
  • Training
  • Risks surveillance and business development strategy

Eric TREPO
Coordinator

WP5 Introduction

Project Management, IP Management, Data Management, and Ethics

In WP5, we navigate the ethical, administrative and technical complexities of GENIAL. Our first task is ensuring that our research respects all ethical considerations and the General Data Protection Regulation (GDPR). We’ll manage all aspects of the projects, from activity scheduling, quality checks, and financial coordination to contractual management and conflict resolution. Our goal is a well-organised project that meets its objectives, delivers results, and comlies with EU regulations.