ELPA is part of the new medical, scientific project GENIAL responsible for communication and dissemination.

Alcohol-related hepatocellular carcinoma (ALD-HCC) is, in Europe, the leading cause of liver cancer. ALD-HCC has a median 5-year survival rate of 15%. Yet, the prognosis is driven by the tumor stage, with curative options providing a 5-year survival exceeding 70% for early-stage HCC (<20% of cases). Therefore, interventions aiming at improving prevention and early detection are key. ALD-HCC results from the interplay between environmental determinants and genetic variations. A comprehensive characterization of environmental factors linked to ALD-HCC is still lacking. The 1st genome-wide association study of ALD-HCC was recently performed, identifying predisposing genetic variations. However, their role in alcohol-related liver carcinogenesis needs clarification, and the genetic architecture of ALD-HCC remains mostly unknown. GENIAL brings together partners with unique expertise in clinical hepatology, single-cell and spatial multi-omics, artificial intelligence (AI) and communication and dissemination capacities. The aim is to 1) portray genetic and environmental determinants promoting ALD-HCC; 2) evaluate how they interact at the cellular level in human samples and preclinical models to get novel insights into liver carcinogenesis and identify chemopreventive targets; and 3) assess how these determinants modulate the ALD-HCC risk in prospective cohorts of patients included in HCC surveillance programs. Environmental factors will be comprehensively characterised in an ongoing clinical trial designed to evaluate alternative methods for early-stage HCC detection. Finally, AI models, reaching the minimal viable product stage by the end of GENIAL, will be used to integrate genetic and non-genetic information to develop novel, cost-effective strategies towards prevention and early-stage detection in at-risk individuals. The kick-off meeting was organised in Brussels on March 21-22, 2022.