halt-RONIN: Discovering chronic inflammation biomarkers that define key stages in the Healthy-to-NASH (non-alcoholic steatohepatitis) transition to inform early prevention and treatment strategies

Non-alcoholic fatty liver disease (NAFLD) is a multifactorial chronic inflammatory disease that is prevalent in 1 of 4 individuals with a significant personal, socioeconomic and healthcare burden, especially at the later, more severe inflammatory stage of disease - non alcoholic steatohepatitis (NASH). Despite the severe negative impact of the disease on society, NAFLD remains difficult to diagnose and treat. Additionally, the molecular mechanisms underlying the transition from health to fatty liver to NASH remain poorly understood due to the lack of models that faithfully reflect the complexity of human disease. Hence, Halt-RONIN aims to uncover the early triggers of disease initiation and complex mechanistic drivers of disease progression by implementing a systems biology approach with integrative disease modelling resulting in opportunities for the improvement of the existing detection methods, providing a blueprint to inform personalized intervention strategies and drug discovery for NAFLD. To achieve this goal, Halt-RONIN will combine experimental data from advanced in vitro and in vivo models with multimodal data from extensive human NAFLD cohorts and biobanks and use in silico machine learning approaches, to discover new biomarkers and molecular targets specific to each stage of the health-to-disease transition. By validating no project summary