UMH to Study Causes of Cognitive Decline in People with Liver Cirrhosis

The Hepatic and Intestinal Immunobiology Group at the Miguel Hernández University of Elche (UMH) will investigate how to reverse memory and cognition problems associated with many patients with liver cirrhosis, particularly in aging. The project, named EVENing, has received funding from the Generalitat Valenciana through the Prometeo program and will explore the relationship between liver and brain inflammation.

EVENing is co-directed by UMH researchers Rubén Francés and Esther Caparrós from the Department of Clinical Medicine, the Institute for Research, Development and Innovation in Healthcare Biotechnology of Elche (IDiBE UMH), and the Networked Biomedical Research Centre for Liver and Digestive Diseases (CIBERehd) of the Carlos III Health Institute.

Liver cirrhosis is a chronic disease where continuous liver inflammation eventually affects other organs. In elderly individuals, this process is often associated with neurocognitive complications: memory, attention, or processing speed problems that impact their autonomy and quality of life.

In this context, the EVENing project is based on a key idea: "During cirrhosis, some adaptive immune system cells, particularly T cells, become dysfunctional and accumulate in the damaged liver and also in the brain, disrupting the balance of the so-called liver-brain axis," explains UMH researcher Esther Caparrós. The expert points out that although T cells are essential for defense against infections, their dysfunction contributes to the chronic inflammation that characterizes cirrhosis and triggers a cascade of problems throughout the body.

"One of these complications is that inflammation spreads to the brain, and there is increasing evidence that it may be one of the causes of memory and cognition problems experienced by many cirrhosis patients, especially the elderly; if the person is sick and elderly, these deficits can significantly impair their quality of life and make them dependent," adds Caparrós.

"The central hypothesis of the EVENing project is that this T cell dysfunction can be corrected by 'reprogramming' the dialogue they maintain with the liver and the nervous system," details the researcher. To achieve this, the team will focus on two major communication pathways.

"T cells not only respond to immune signals but also to nervous system signals, such as neuropeptides. If we can restore the way LSEC and T cells interact, and at the same time recover the ability of T cells to correctly perceive these nervous signals, we could correct their dysfunctional response and restore balance in the liver-brain axis of elderly cirrhosis patients," summarizes the researcher.

"To demonstrate that this reprogramming is possible, we first need to understand exactly where T cells go: we will track them from their origin in the liver and during their migration to the brain and intestine, observing how their activity changes as cirrhosis progresses and the body ages," explains UMH researcher Rubén Francés.

UMH researchers will compare results obtained in animal models with human samples from biobanks. The team will compare liver biopsies from cirrhosis patients with cognitive impairment to those from cirrhotic patients without such complications, aiming to identify "immune signatures" that could serve as risk markers and future therapeutic targets.

Although this research is still far from clinical application, its goal is to lay the foundations for interventions that allow targeted modulation of T cells, restore homeostasis of the liver-brain axis in elderly cirrhosis patients, and reduce the impact of neurocognitive complications associated with this disease.

The EVENing project (Immune reprogramming to balance the liver-brain axis T cell compartment during aging in cirrhosis) is funded by the Ministry of Education, Culture, Universities, and Employment of the Generalitat Valenciana under the Prometeo 2025 program for excellence research groups (CIPROM/2024-19), with a budget of 600,000 euros and a duration of four years, until August 2029.