GRIP on MASH will address the unmet public health need of reducing disease burden and comorbidities associated with Metabolic dysfunction-Associated Steatotic Liver Disease (MASLD). Together with seven medical technology, pharmaceutical and biotechnology companies, we will devise a sustainable and scalable GRIP on MASH Platform that will enable access to at-risk patients developing or having MASLD through the early detection of this condition at the primary care level. This Platform will allow A) the early detection of patients with MASLD: distributed in 12 European Centers of Excellence (CoEs), 10,000 patients at high risk of MASLD - defined as patients with type-2 diabetes mellitus, metabolic syndrome, obesity or arterial hypertension - will be screened and characterized; B) better patients’ stratification: the Platform will comprise artificial intelligence-based decision support tools that will make use of existing and novel biomarkers/biomarker combinations. Their predictive accuracy will be tested at the primary care level; there we will perform multi-OMICs analysis (proteomics, lipidomics, metabolomics, genomics, metagenomics and fluxomics) in fasted blood samples and we will explore imaging biomarkers/organ-on-a-chip to find future non-invasive diagnostic alternatives for the current standard (liver biopsies); and C) personalized lifestyle advice, by exploring evidence-based lifestyle features and the effect of nutritional recommendations: among the cohorts at the CoEs, we will use validated questionnaires to assess physical activity, diet, sleep, smoking, alcohol consumption, and perception of stress. Integrating patients’ perspectives with the participation of two patient organizations, the trustworthiness and sustainability of our GRIP on MASH Platform will be assessed by investigating potential economic, ethical and regulatory barriers to its future adoption. GRIP on MASH will change healthcare practice in MASLD and reduce the disease burden for patients.

Strongly associated with the epidemics of obesity and type 2 diabetes that are testing healthcare systems worldwide, Non-Alcoholic Fatty Liver Disease (NAFLD) is an increasingly common cause of advanced liver disease that is characterized by substantial inter-patient variability in severity and rate of progression. It is currently assessed by liver biopsy, an invasive, costly and risky procedure. The lack of noninvasive biomarkers has hampered patient care and impeded drug development by complicating conduct of clinical trials.The overarching aim of LITMUS is to develop, robustly validate and advance towards regulatory qualification biomarkers that diagnose, risk stratify and/or monitor NAFLD/NASH progression and fibrosis stage. This will be achieved through a goal-oriented, tri-partite collaboration delivering a definitive and impartial evaluation platform for biomarkers, bringing together: (i) End-users of biomarker technologies (clinicians with expertise in NAFLD and the pharmaceutical industry)? (ii) Independent academics with expertise in the evaluation of medical test/biomarker performance? and (iii) Biomarker researchers and developers (academic or commercial). LITMUS has the demonstrable capability to fulfil the IMI call remit. Built upon foundations laid by the EU-funded FLIP/EPoS projects and long-established, successful scientific collaborations amongst many of Europe’s leading clinical-academic centres, LITMUS is at a unique advantage due to its existing large-scale patient cohorts, bioresources and multi-omics datasets. Consortium members are internationally recognised experts with substantial relevant expertise supporting the program’s clear focus on biomarker identification, validation and accelerating EMA/FDA qualification. Thus, LITMUS is powered to provide clarity on biomarker validity for NAFLD at scale and pace: supporting drug development and the targeting of medical care and limited healthcare resources to those at greatest need.

Liver cirrhosis is a very common and severe chronic disease, responsible for high morbidity, impaired quality of life, major healthcare costs, and poor survival, causing an estimated 170,000 deaths per year in Europe. Liver cirrhosis is preceded by a long period of slowly developing, asymptomatic, liver fibrosis; most commonly caused by non-alcoholic fatty liver disease (NAFLD, related to obesity and type 2 diabetes), alcohol, and hepatitis B or C virus infection. There is no treatment available to reverse advanced liver cirrhosis. However, if fibrosis could be detected early, all of the major causes are still amenable to prevention and treatment. Early diagnosis of liver fibrosis in the general population is therefore crucial for the estimated 10 million Europeans with undetected liver fibrosis. The LiverScreen project aims to develop a targeted screening methodology to identify persons with asymptomatic liver fibrosis and cirrhosis among the general population. This methodology involves: 1) identification of groups from the general population at high risk of having chronic liver disease, 2) screening their liver stiffness with the innovative transient elastography (TE) technology (until now only validated in patients with known liver disease) for diagnosis, and 3) determining the right follow-up screening regime. Within the LiverScreen project 8 European countries will collaborate and perform research in over 34,000 subjects to develop the screening methodology and demonstrate its accuracy, clinical value, cost-effectiveness, acceptability, and potential to be implemented by healthcare systems throughout Europe. Using the LiverScreen program, diagnosis at an early stage can stop liver disease progression and have a subsequent long-term impact on liver disease morbidity and mortality and the associated societal burdens in terms of economic costs and health inequity. The estimated cost reduction ranges from €850 to €4,000 per quality-adjusted life-year gained.

Liver cirrhosis and liver cancer are common and responsible for high morbidity, impaired quality of life, major costs for healthcare systems, causing 300K deaths per year in Europe. Predominant etiological factors are obesity, type2 diabetes, and increased alcohol in-take, which are all on the rise. It is predicted that healthy life expectancy will decrease in Europe over the next 30 years because of deaths due to liver disease. Liver cirrhosis develops after a very long period of asymptomatic liver fibrosis, staying undetected until patients develop severe complications due to cirrhosis or liver cancer. Currently the only effective treatment available is liver transplantation which is not applicable to all patients. If fibrosis is detected early, to target the course of liver disease, then liver fibrosis is reversible. The LIVERAIM project concentrates a team of renowned clinical centres and Industrial partners, including SMEs, with great expertise in the field of Liver Disease, the aim being to design and validate a screening platform with biomarkers for population screening to use across Europe. The objective is to identify liver disease early and apply personalized therapeutic interventions. A large number of existing biomarkers will be tested for fibrosis prediction accuracy using biobank plasma samples from 40,000 subjects from previous H2020 EU-funded cohorts. LIVERAIM will develop a screening platform with biomarkers using AI for personalized early diagnosis of fibrosis to be validated in a RCT of 100K subjects from 6 representative EU countries. The platform will be linked to tailored, personalized therapeutic interventions to halt fibrosis progression. With LIVERAIM, early diagnosis and personalized intervention can stop liver disease progression, help decrease morbidity and mortality and the associated societal burdens both economic and health inequity.