An international study, led by scientists from the Center for Applied Medical Research (CIMA) at the University of Navarra (Spain) and from the University of Pittsburgh (USA), revealed the causes of acute alcoholic hepatitis resulting in liver failure. Until now the only possible treatment for these patients was through corticosteroids and their efficacy was very limited. The study revealed that a protein, HNF4A, could be the key to new methods of treating the disease. The results have been published in the latest issue of the scientific journal Nature Communications.
Alcoholism is a serious problem in Western society and one of the reasons for the increase in mortality due to liver disease. One of the diseases with the worst prognosis is acute alcoholic hepatitis, a syndrome with subacute liver failure. Currently, it is estimated that more than half of deaths from liver disease in the European Union are due to excessive alcohol consumption.
“The only treatment indicated for these patients is corticosteroids, a therapy implanted since the 1970s and which has a very limited efficacy,” explains Josep María Argemí, first author of the work and researcher at the University of Pittsburgh (USA). According to the scientist, “these patients are not usually candidates for liver transplantation, because they have an active addiction to alcohol consumption. In addition, this disease has been stigmatized by both society and the scientific community and there have been no deep studies on its biological mechanisms. ”
The work done by this team is the first to molecularly characterize which are the pathways responsible for liver failure in people with acute alcoholic hepatitis. “Specifically, RNA sequencing techniques, DNA methylation analysis, plasma proteomic analysis and analysis of genomic sequence variations (GWAS) have been used to correlate molecular patterns with patient clinical data,” Argemí explains.
The pieces in the liver failure puzzle
As Matías Ávila, director of the Hepatology Program of the Summit and co-author of the work, points out, “we verified that the liver cell (hepatocyte) is transformed into a ‘selfish’ cell concerned only about its own survival, instead of performing the essential functions for the organism: glucose synthesis, synthesis of coagulation factors or bilirubin secretion, urea metabolization. As a consequence of this change, the patient enters into a situation of liver failure, which quickly leads to multi-organ failure.”
This study demonstrates that a central piece in the puzzle of liver failure due to acute alcoholic hepatitis is the transcription factor HNF4A. “In a healthy person, this protein is responsible for coordinating the functions of the hepatocyte. However, in patients with liver failure there is an alteration of their processing (splicing) and an inhibition of the genes that depend on it,” the researchers point out.
“We hope that this molecular information that we offer to the scientific community will open the door to new treatments that help us save lives and give our patients a second chance,” conclude Argemí and Ávila.