Chronic liver disease significantly worsens when the liver’s immune system remains in a state of overactivity, resulting in persistent inflammation and scarring. Research conducted by scientists at Universidad Miguel Hernández in Spain highlights the role of a single inflammatory switch that may aid in repairing liver damage associated with cirrhosis. The study focuses on the impact of Platelet-Activating Factor (PAF) and its receptor on the progression of liver disease.
Cirrhosis, a serious and progressive condition, involves the gradual replacement of healthy liver tissue with scar tissue, leading to a loss of both structure and function. Inflammation driven by liver macrophages—key immune cells—exacerbates this damage. These cells produce elevated levels of PAF, which contributes to increased portal vein pressure and reduced blood flow in other areas of the body. Current treatments primarily address complications rather than the underlying causes of liver damage, underscoring the urgent need for innovative approaches.
The research team, led by Rubén Francés Guarinos, aimed to investigate the role of PAF and its receptor (PAF-R) in liver cirrhosis. “Our main objective was to understand the role of platelet-activating factor (PAF) and its receptor (PAF-R) in liver cirrhosis, a disease characterized by progressive liver damage accompanied by intense chronic inflammation,” explained Guarinos.
To conduct the study, researchers examined both patients with cirrhosis and mice with chemically induced cirrhosis. Mice were treated with either a drug blocking the PAF-R receptor or a DNA methylation inhibitor for two weeks prior to undergoing surgery. Following these procedures, the team assessed liver immune cells to analyze changes in DNA activity and measured levels of key receptors.
The findings revealed a significant alteration in gene regulation in cirrhotic subjects. Specifically, the removal of chemical markers from the PAF-R gene leads to its overactivity, prompting liver immune cells to produce excess PAF-R receptors. This process intensifies inflammation, resulting in greater liver damage. Notably, the team demonstrated that administering the drug BN-52021 not only mitigated liver injury but also improved blood vessel function in the treated mice, restoring balance to the liver’s immune and inflammatory responses.
“Taken together, these findings suggest that drugs capable of blocking PAF action, such as BN-52021, could represent a new therapeutic line for liver cirrhosis,” stated researcher Enrique Ángel Gomis. The potential of such therapies transcends merely suppressing inflammation, aiming instead at addressing the molecular switches that render the liver more susceptible to damage.
In cirrhosis, the PAF-R gene is excessively activated due to epigenetic changes. Future therapeutic strategies could involve designing treatments that restore or correct these epigenetic controls, thereby preventing the overproduction of PAF-R at its source. By calming the liver’s immune cells before they initiate damaging inflammatory responses, researchers anticipate a reduction in scarring and enhanced protection of blood vessel function.
This approach signifies a shift from merely managing the symptoms of cirrhosis to developing epigenetic-based therapies that could fundamentally alter the liver’s immune response. The findings of this significant study were published in the journal Biomedicine & Pharmacotherapy, highlighting the potential for new, more effective treatments for chronic liver disease.
