Liver cirrhosis: A silent killer claiming over a million lives each year. But what if there was a way to fight back against the damage? Researchers at Miguel Hernández University of Elche (UMH) in Spain have discovered a promising strategy to reduce liver damage and improve how the liver functions in people with cirrhosis. This groundbreaking research, published in Biomedicine & Pharmacotherapy, has pinpointed a key inflammatory mechanism that contributes to liver injury, potentially opening doors to new treatments for this devastating disease.
The study, spearheaded by Rubén Francés Guarinos, involved collaboration with several prestigious institutions, including the Institute for Health Biotechnology Research, Development and Innovation of Elche (IDiBE UMH), the Hepatic Vascular Biology Group at Hospital Clínic of Barcelona, and the Spanish Biomedical Research Network in Hepatic and Digestive Diseases (CIBERehd).
The primary goal of the research was to understand the role of platelet-activating factor (PAF) and its receptor (PAF-R) in liver cirrhosis. Cirrhosis is characterized by progressive liver damage and chronic inflammation. The researchers also investigated whether blocking this inflammatory pathway could be an effective way to improve liver function in patients.
Liver cirrhosis is a serious condition where healthy liver tissue is gradually replaced by scar tissue, leading to a loss of structure and function. Globally, it affects over one million people and accounts for approximately 2.4% of all deaths. The impact on public health is significant. Sadly, current treatments often focus on managing complications rather than addressing the underlying biological mechanisms that drive liver damage.
To tackle this, the researchers compared different experimental treatments in both healthy and cirrhotic liver tissue. They administered a PAF antagonist, BN-52021, which blocks the PAF-R receptor, and an inhibitor called Aza, which modifies the epigenetic regulation of the receptor. Advanced analyses, like DNA methylation profiling, were used to understand why PAF-R expression is abnormally increased in cirrhosis.
The study used liver samples from patients with cirrhosis and a mouse model of experimental liver injury. The focus was on hepatic immune cells called Kupffer cells, which play a central role in inflammatory responses in the liver.
And this is the part most people miss... The research revealed that an epigenetic mechanism drives the increased expression of PAF-R in these inflammatory cells. In cirrhosis, demethylation of the PAF-R gene removes a chemical mark that usually keeps its expression in check. This overactivates the gene, increasing the number of PAF-R receptors and amplifying inflammation and liver damage.
The results also showed that treatment with the PAF antagonist BN-52021 effectively reduced structural liver damage and improved hepatic vascular function in cirrhotic mice. This treatment also helped rebalance immune and inflammatory responses within the liver.
This is where it gets controversial... These findings suggest that drugs blocking PAF action, such as BN-52021, could be a new treatment for liver cirrhosis. The research also opens the door to therapies that correct the epigenetic mechanisms regulating PAF-R, with the goal of controlling inflammation and liver damage at their molecular origin.
Enrique Ángel Gomis, the first author of the study, is a UMH researcher.
What are your thoughts? Do you think this research could lead to effective treatments for liver cirrhosis? Share your opinions in the comments below!
