Fuerstenfeldbruck, Germany, February 04, 2019 --(PR.com
)-- In the 6-year-long EU-funded MICROB-PREDICT project, world-leading microbiome experts, technology leaders, clinical specialists, patient organisations (ELPA) and the European Association for the Study of the Liver (EASL) join forces to understand how the human microbiome contributes to the development of liver decompensation and ACLF.
High-quality data of more than 10,000 subjects from three existing EU-funded projects (GALAXY, LIVERHOPE, PREDICT) will be analysed to design novel, microbiome-based tests and diagnostic tools.
The 75-month project aims to develop improved and more personalized therapies for patients suffering from cirrhosis and ACLF.
The Fatal Course of Decompensated Liver Cirrhosis & ACLF
End-stage chronic liver disease (cirrhosis) is a major cause of morbidity and mortality, and has a large socioeconomic impact because of high health care costs and the patients’ inability to work or seek employment. Patients show symptoms, start suffering, and eventually die of chronic liver cirrhosis when the body essentially can’t compensate the mis- or dysfunctional liver condition any longer. That’s why it’s called decompensated (as opposed to compensated) cirrhosis. Decompensated cirrhosis is defined by accumulation of fluid in the abdomen (ascites), impaired brain function (hepatic encephalopathy), and often also bleeding in the digestive tract (gastrointestinal haemorrhage). Eventually, it progresses to acute-on-chronic liver failure (ACLF) and death.
Genetic predisposition and/or infections can increase the risk for decompensated cirrhosis and worsen its prognosis. The gut microbiome consists of all bacteria, viruses, parasites, fungi and archaea bacteria that colonize the gastrointestinal tract. Aberrations in the gut microbiome, a damaged gut-body barrier, excess bacteria crossing that barrier (microbial translocation), and systemic inflammation can trigger decompensated cirrhosis and its progression to ACLF. A recent multi-centre study by the European Foundation for the study of Chronic Liver Failure (EF-CLIF, Barcelona) demonstrated that bacterial infections are common precipitating events for ACLF in Western countries, and confirmed the high mortality rate of ACLF.
How Patients With Cirrhosis or ACLF May Benefit From MICROB-PREDICT
MICROB-PREDICT aims to develop personalised, microbiome-based treatment strategies to prevent and treat ACLF and reduce mortality by investigating the human gut microbiome. The goal is to identify predictors and mechanisms associated with the development of decompensated cirrhosis and its progression to ACLF. The need for personalised treatment strategies becomes apparent when considering that there are substantial, yet still largely unexplained, individual differences in developing decompensated cirrhosis and ACLF. At the same time, this observation bears the chance for more effective, more individualised and more targeted treatments.
The pan-European research project will integrate microbiome results and other patient data from previous large-scale studies, such as GALAXY, LIVERHOPE and PREDICT, combining more than 200,000 data points from about 10,000 subjects. A comprehensive data base will be generated, including data from stool, blood, saliva, mucosa and urine samples over the course of the disease, allowing for a novel longitudinal analysis, thereby clearly providing added value over the previous studies. MICROB-PREDICT will identify and validate microbiome-based individual biomarkers and predictors of a) healthy, low-risk conditions, b) decompensated cirrhosis and progression to ACLF, and c) treatment response. In addition, the role of environmental factors (e.g. exposure to pollutants), lifestyle (e.g. smoking), diet (e.g. alcohol consumption), comorbidities, ageing, geographic differences and socio-economic factors will also be taken into account.
Gained knowledge will be translated into clinical tests for doctors and every-day tools for liver-disease patients, such as point-of-care (POC) diagnostic tests and state-of-the-art nanobiosensors for smartphone-based patient self-monitoring. MICROB-PREDICT also tries to identify and validate “biomarker signatures” that reliably predict the therapeutic response to treatment with human albumin in a randomized clinical trial (ALB-TRIAL).
The MICROB-PREDICT Consortium
Professor Dr. Dr. med. Jonel Trebicka (EF-CLIF, Barcelona, and Goethe University Frankfurt) spearheads and coordinates MICROB-PREDICT. The Kick-Off Meeting took place at the end of the month, from January 28th to 30th 2019, in Barcelona, Spain. The following 22 institutions participate in this multi-centre project:
· Academisch Ziekenhuis Leiden
· Biobyte Solutions GmbH
· Commissariat à l’Energie Atomique et aux Energies Alternatives
· concentris research management GmbH
· Debreceni Egyetem
· European Association for The Study of the Liver
· European Foundation for The Study of Chronic Liver Failure
· European Liver Patients Association
· European Molecular Biology Laboratory
· Fundació Clínic per a la Recerca Biomèdica
· Fundació Institut Català de Nanociència i Nanotecnologia
· Institut National De La Recherche Agronomique
· Johann Wolfgang Goethe-Universität Frankfurt Am Main
· Katholieke Universiteit Leuven
· King’s College London
· Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V.
· Odense Universitetshospital
· Universitat de Barcelona
· Universitetet I Oslo
· University College London
· University of Copenhagen
· Vaiomer SAS
Dr. Minneke Coenraad
This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No. 825694.