Why it matters
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. 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). Patients show symptoms, start suffering, and eventually it progresses to acute-on-chronic liver failure (ACLF) when the body essentially can’t compensate the dysfunctional liver condition any longer. That’s why it’s called decompensated, as opposed to compensated, cirrhosis. Worldwide, 1.2 million people die of cirrhosis every year, while less than 10% of the research in the field focuses on decompensated cirrhosis and ACLF. Therefore, it is crucial to develop novel treatments and help cirrhosis patients earlier, faster and better.
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.
In this 6-year-long research project, world-leading microbiome experts, technology leaders, clinical specialists, the European Liver Patients Organisation (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.