Extracellular vesicles to detect fatty metabolic liver disease

A recent study has demonstrated the possibility of using markers from the liver, and present in the blood, as a non-invasive method to detect and assess the severity of metabolic fatty liver disease (or MetHE) from a blood sample. To date, tests require performing a biopsy of the liver.

The discovery is the work of the SeLiver group, from the Institute of Biomedicine of Seville (IBiS) in Spain, led by Dr. Manuel Romero.

Specifically, the research demonstrates the possibility of using the EpCAM+ CD133+ extracellular vesicles as biomarkers of severity of the pathology or of the transition from steatosis to steatohepatitis in a non-invasive manner.

The study analyzed samples from 130 patients with metabolic hepatic steatosis from the Virgen del Rocío University Hospital and the Valladolid University Clinical Hospital previously diagnosed by liver biopsy to corroborate their diagnostic capacity.

Professor Javier Cubero from the Complutense University of Madrid (UCM) and Dr. Javier Vaquero from the Gregorio Marañón Hospital in Madrid, who belong, together with the SeLiver group, to the Biomedical Research Center for Liver Diseases Network, have also collaborated in the research. and Digestive (CIBEREHD), in Spain all these entities.

In the collaboration, a murine model was used, with transgenic mice, to confirm the hepatic nature of these extracellular vesicles.

EpCAM and CD13 expression in liver tissue from a patient with fatty metabolic liver disease. An electron microscopy image of extracellular vesicles isolated from patient blood is represented in the lower corner. (Images: IBiS)

In search of a non-invasive diagnostic test

“So far there is no biomarker [una molécula o sustancia que actúe de “chivato”] for the diagnosis of steatohepatitis, with liver biopsy being the only diagnostic method”, explains Dr. Rocío Muñoz, postdoctoral researcher in the SeLiver group of the Seville Institute of Biomedicine (IBiS), who leads a line of research on the use of Extracellular vesicles as a biomarker in metabolic hepatic steatosis.

“Biopsies are invasive tests, with a high cost and possible complications,” continues the expert. “Hence the need to look for prognostic and diagnostic biomarkers.” This is especially relevant in the case of metabolic hepatic steatosis, since not only must the disease be diagnosed, but it is also necessary to evaluate a prognosis before it occurs, as soon as possible, to implement contingency measures if necessary. .

Research teams have verified the possibility of using extracellular vesicles for this purpose, avoiding other more invasive tests. These vesicles are structures from cells that are released into the bloodstream carrying various substances throughout the body. They function as cellular messengers and carry in their membranes certain molecules of a protein nature that serve for the organism to identify them. Two of these molecules, known as markers, are the protagonists of the research.

“EPCAM and CD133 are specific markers […] involved in the development of liver cancer”, points out the expert. As she explains, hepatocytes, or mature cells, are responsible for repairing and regenerating the liver. However, when the damage exceeds its regenerative capacity, so-called liver progenitor cells come into play. They release into the blood these extracellular vesicles marked as EpCAM+ CD133+ (so called because these markers are detected in them).

“We have seen that these vesicles rise significantly in the presence of inflammation, that is, that they are found in greater numbers, in patients with steatohepatitis compared to those with simple steatosis”, continues the doctor. In other words, the appearance of these vesicles is directly related to the action of the cells that “work” when the damage is too great in the liver, pointing towards metabolic fatty liver. “This shows us the usefulness of these EpCAM+ CD133+ extracellular vesicles as a biomarker of severity of the pathology, or of the transition from steatosis to steatohepatitis.”

“This new biomarker [las vesículas extracelulares EpCAM+ CD133+] it would make it possible to diagnose the presence of steatohepatitis in a non-invasive way”, says Sheila Gato, pre-doctoral researcher in the SeLiver group at IBiS and co-author of the study. “At the moment, there is still a need to standardize the processing and determination of these vesicles and then implement it in routine clinical practice.”

The study is titled “Role of EpCAM+ CD133+ extracellular vesicles in steatosis to steatohepatitis transition in NAFLD”. It has been published in the academic journal Liver International and has also been selected as the best of the American Congress for the Study of the Liver (AASLD 2022). (Source: IBIS)