Scientists find why the liver may not heal even after you stop drinking

Scientists have discovered why the liver may not heal properly even after a person stops drinking excessively. The liver, a remarkable organ capable of self-repair and regeneration, can struggle to restore itself when damaged by alcohol. Researchers from the University of Illinois Urbana-Champaign, Duke University, and the Chan Zuckerberg Biohub Chicago found that lingering inflammation disrupts a crucial process called RNA splicing, which is necessary for cells to convert genetic instructions into functional proteins.

Published in Nature Communications, these findings could lead to new diagnostic and treatment methods for severe alcohol-associated liver disease, which is the leading cause of liver-related deaths globally, resulting in approximately 3 million deaths annually. Despite the liver's remarkable regenerative abilities, it stops functioning and regenerating in patients with alcohol-related hepatitis and cirrhosis, even after they cease alcohol consumption.

The researchers discovered that liver cells become trapped in an abnormal middle state, unable to function normally or complete the regeneration process. This condition is caused by inflammation disrupting RNA splicing, which in turn affects protein production and localization within the cells. The team identified a possible driver of these errors: low levels of a protein called ESRP2.

ESRP2 helps ensure proper RNA splicing, and its deficiency in alcohol-damaged liver cells results in mis-spliced RNA and altered molecular instructions that direct proteins to the wrong cellular locations. This mis-localization prevents key proteins from functioning correctly, ultimately contributing to liver failure.