Chronic liver disease affects about 29-million Europeans accounting for about 170,000 deaths at a cost of around €15.8bn. This chronic non-communicable disease is increasing at an alarming rate due to increasing European obesity, alcohol use and ageing. The three main causes of the disease; alcohol, fatty liver and viral hepatitis are amenable to prevention and treatment. Gut-derived endotoxins and bacterial translocation are central factors implicated in the pathogenesis of fatty liver disease and, the development and progression of cirrhosis. In cirrhosis, current state-of-the-art therapy to prevent recurrent complications of advanced cirrhosis is to use poorly absorbed antibiotics but long-term antibiotic therapy has problems associated with bacterial resistance, infection with resistant organisms and the cost. Treatment of fatty liver and modulation of bacterial translocation in early cirrhosis to prevent complications is an unmet need. Our academic-industrial consortium has developed a novel, patented, safe and cheap nanoporous carbon that modulates the effects of bacterial translocation in animal models of liver disease. Our feasibility studies demonstrate that this product advances the current state-of-the-art, is a TRL 4/5 and is now ready for validation through clinical trials. We propose to investigate the safety and efficacy of this novel nanoporous carbon in patients with fatty liver disease and cirrhosis. If successful, we will be able to confirm an innovative, cost-effective and novel strategy for the management of this chronic disease in a European population. Exploitation of the results of the CARBALIVE project will support the continued development of this carbon through additional private and public sector investment. The use of this innovative therapy is expected to reduce the economic burden of the disease in Europe, allow patients to achieve enhanced quality of life, improve survival, and allow many patients to return to economic productivity.

In Europe, about 30,000 people die every year from alcohol related cirrhosis, a form of chronic, non- communicable disease. The patients that are at highest risk of death are those with superimposed alcoholic hepatitis (AH) who do not respond to therapy and develop acute on chronic liver failure (ACLF), a newly described syndrome characterised by multiorgan failure. Treatment of ACLF is an unmet need. Based upon their clinical and pre-clinical studies, the A-TANGO consortium aims to perform Phase 2 clinical trials of a novel, patented and innovative therapeutic strategy by repurposing a toll-like 4 receptor antagonist (TAK242, Technology Readiness Level (TRL) 8), which targets inflammation, and combining it with granulocyte colony-stimulating factor (G-CSF, TRL9) that improves hepatocyte proliferation (G-TAK, TRL4). A successful trial will advance G-TAK to TRL8. Additionally, A-TANGO aims to discover novel biomarkers for patient selection and defining prognosis, building health economics models and reimbursement strategies to allow maximal dissemination and exploitation. The A-TANGO Consortium includes the inventors of G-TAK (UCL, Charité, ULEI and LUMC) and will deliver the project aims through EFCLIF, which has a network of 110 European hospitals. YAQ and HPX are SME’s that own the background IP and will ensure regulatory approval, study Sponsorship and drug supply. APHP and IMAC will deliver the economic models. Concentris will manage the project and together with EASL, CHX and ELPA will engage with patients, initiate widespread dissemination activities and allow exploitation of the results. Gender balance will be maintained throughout the project duration. A-TANGO will achieve the expected impacts of producing meaningful advances in clinical practice by reducing the mortality and improving the quality of life of patients with ACLF whilst reducing disease burden of individual patients and health care systems following validation in late stage clinical trials.