An international study led by Bernbd Schnabl of the University of California San Diego with the participation of the Vall d'Hebron Research Institute (VHIR), the Clinical Hospital and the CIBER of Hepatic and Digestive Diseases (CIBEREHD), has discovered new mechanisms of alcoholic hepatitis (HA), the most severe form of alcoholic liver disease, with particular relevance to the gut microbiota in the development of the disease, and which could open a path for new treatments.Alcoholic hepatitis is currently experiencing a high mortality rate and its treatment is based on the use of corticosteroids, which are ineffective in many cases, and the only cure for it is early liver transplantation.In this research published in Nature by the InTeam Consortium, coordinated by Ramón Bataller of the University of Pittsburgh and which has the participation of CIBEREHD researchers Juan Caballería, of the Clinical Hospital of Barcelona, and with Víctor Vargas and Meritxell Ventura-Cots of the Vall d'Hebron University Hospital in Barcelona, a protein secreted by the Enterococcus Faecalis bacterium, called cytolysin, has been discovered, that circulates in the blood and causes cellular damage to the liver, promoting liver failure. E. Faecalis is a germ that is not found in the normal microbiome but in patients with alcoholic hepatitis accounts for 5.6% of the faecal bacteria.Different parts of the study included 26 controls (social drinkers), 44 at-risk patients, but without alcoholic hepatitis, and 88 who did have the disease, belonging to the InTeam Consortium's network of clinical centers in Spain, United States, Mexico, Britain and France.The study, performed through faecal and serum samples of HA patients and murine models of alcoholic liver disease, showed that patients with E. Fecalis strains producing blood cytolysin in the blood had a higher mortality. Almost 90% of patients - out of a total of 25 - with alcoholic hepatitis and the positive protein died within 180 days of hospital admission, compared with 4% of those with a negative, of a total of 54.According to CIBEREHD researcher Juan Caballería, "thanks to this finding, we find that the detection of the cytolysin gene in feces in these patients could be an optimal biomarker for determining the severity of liver disease and the risk of death, which would mean being able to establish personalized therapies based on the state of this protein."The researchers then transferred feces from people with alcoholic hepatitis with positive and negative cytolysin to alcohol-exposed mice. Animals with cytolysin-positive gut microbiomes developed more severe alcohol-induced liver disease and survived to a lesser extent than mice without cytolysin. Finally, therapy with a bacteriophage targeted against cytolysin-producing E. Faecalis strains helped prevent liver injury."We found that strategies aimed at reducing the action of this protein decreased liver damage in mice exposed to alcohol, so we believe that controlled clinical studies are needed to verify the safety and efficacy of this protein. in patients with severe alcoholic hepatitis using drugs that reduce the release or action of the cytolysin protein"says Dr. Cavalry."In the last part of the study it has been shown that using therapeutic strategies that destroy the cytolysin-producing microorganism was useful in avoiding liver injury in the mouse experimental model. This may open the door to develop and check the usefulness of targeted therapeutic strategies for E. Faecalis and its cytolysin in patients with severe alcoholic hepatitis, "concludes Dr. Víctor Vargas, Senior Consultant of the Hepatology Service of the Vall d'Hebron University Hospital and principal investigator of the Hepatic Diseases group of the Vall d'Hebron Research Institute (VHIR).