Research projects

Identification and modelling of molecular and cellular events of the immune response associated to the appearance of minimal hepatic encephalopathy in cirrhotic patients

19th National Research Competition in Life and Earth Sciences

Intercellular Dialogue and Interactome: Pathological Implications

Senior Researcher : Carmina Montoliu Felix

Research Centre or Institution : Fundación para la Investigación del Hospital Clínico de la Comunidad Valenciana (Fundación INCLIVA)

Abstract

Patients with liver cirrhosis may have minimal hepatic encephalopathy (MHE) with cognitive and motor impairments which reduces their quality of life and lifespan. We propose that a shift in peripheral inflammation triggers MHE appearance. However, the underlying mechanisms and how they impair cognitive function remain unclear.

One of the extracelular components which modulate the inmune system function are extracellular vesicles (EVs). The protein and microRNAs cargo of EVs is altered in pathological situations and contribute to progression of the disease. We believe that the cargo of microRNAs and proteins in EVs from plasma of MHE patients is altered and that this contributes to the changes in the immune system triggering MHE.

We found that about 59% of MHE patients treated with rifaximin improve cognitive function. Rifaximin normalizes changes in the immune system in patients who improve MHE but not in those who do not improve.

To advance in understanding these mechanisms we are addressing the following studies:

1. Isolation and characterization of the plasma EVs from controls and patients.

2. Analyze the role of extracellular vesicles in the changes in immune cell communication in MHE. We are analyzing the cargo of exosomes by proteomics, Western blot and analyzing a panel of 2083 microRNAs. The bioinformatics analysis will identify altered molecules in MHE and the pathways involved.

3. To evaluate the influence of metabolic syndrome manifestations on response to rifaximin in MHE patients, by analyzing: Specific cognitive and motor alterations and Inflammatory parameters associated with metabolic syndrome features and their response to rifaximin.

4. We assess if changes in the protein and/or miRNA cargo of EVs may be a good biomarker for the presence of MHE and for prediction of response and/or resistance to rifaximin.