Strongly associated with the epidemics of obesity and type 2 diabetes mellitus (T2DM) that are testing healthcare systems worldwide, Non-Alcoholic Fatty Liver Disease (NAFLD) is an increasingly common cause of advanced liver disease in the aging population of Europe. NAFLD is a spectrum of hepatic fat accumulation (steatosis); steatosis plus inflammation (non-alcoholic steatohepatitis, NASH); fibrosis/cirrhosis; and hepatocellular carcinoma in the absence of high alcohol consumption. Up to 30% of the EU population have NAFLD, which will be the main aetiology underlying liver transplants by 2020. However, NAFLD is characterized by substantial inter-patient variability in severity and rate of progression. What determines this is unknown. A large population is at risk, but only some experience morbidity. NAFLD severity is currently best assessed by liver biopsy, an invasive, costly and risky procedure - factors that hinder treatment. There is a need to understand the biological and environmental factors that drive inter-patient variability and to develop robust and more acceptable methods for diagnosis, risk stratification and therapy so that effective medical care may be targeted to those that will benefit most. The overall EPoS concept is that improved understanding of pathogenic processes and drivers of disease progression will best be achieved when multiple ‘omics’ approaches are applied to a single cohort of patients to build a multi-dimensional record of how systems are perturbed across the entire spectrum of disease. NAFLD sits at the intersection of key biological processes: carbohydrate/lipid homeostasis, immune/inflammatory activation, wound healing/fibrosis and cancer biology. Once completed, EPoS promises to deliver a substantial and definitive atlas of pathophysiological variation across a spectrum of progressive liver disease. Translation of these findings will therefore impact on closely related pathologies including T2DM and cardiovascular disease.

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.