Study finds protein which could prevent multi-organ failure in patients with acute liver disease

Scientists have identified a protein in the immune system that could potentially help prevent multi-organ failure in patients with severe liver injury.

Researchers explained that damage to one part of the body can trigger aging and cell failure, which may spread to other organs. This process, known as senescence, occurs when cells become dysfunctional and stop working effectively. While senescence is commonly associated with aging, it can also be triggered by disease at any stage of life.

In cases of acute liver disease, senescence in liver cells can cause irreparable damage, leading to liver failure and potentially triggering failure in other organs.

The study, led by researchers at the University of Edinburgh, UK, found that in mice and human liver tissues from patients with acute liver disease, senescence not only affected the liver but also spread to other organs, including the kidneys and lungs. This systemic spread of senescence increases the risk of multi-organ failure and the need for a liver transplant.

The team also identified a key biological process involving TGF-β, a protein related to the immune system. Blocking the activity of TGF-β was shown to prevent liver cell damage from spreading to other organs.

Published in Nature Cell Biology, the study provides new insights into why severe liver injury leads to the failure of multiple organs, including the brain and kidneys, and increases the risk of death. According to Rajiv Jalan, a professor of hepatology at University College London, UK, and a study author, the findings have significant clinical implications.

“We were able to validate these novel and exciting observations in patients, which provides a pathway to develop blood-based biomarkers to identify those at risk, as well as new therapies for severe liver disease,” said Jalan.

While there is currently no test to predict how sudden liver failure will progress, the researchers suggest that monitoring liver cells could help identify patients most at risk, including those who may require a liver transplant.

The authors concluded, “We identify the TGF-β pathway as a critical mediator of the systemic spread of senescence and demonstrate that inhibiting TGF-β prevents senescence transmission to other organs, thereby preventing liver senescence-induced kidney dysfunction.”