On Sept. 10, 2025, researchers at University of Illinois Urbana-Champaign and collaborators at Duke University and the Chan Zuckerberg Biohub Chicago reported that excessive alcohol consumption can disrupt the liver’s unique regenerative abilities by trapping cells in limbo between their functional and regenerative states, even after a patient stops drinking.

This in-between state is a result of inflammation disrupting how RNA is spliced during the protein-making process, the researchers found, providing scientists with new treatment pathways to explore for the deadly disease. The researchers published their findings in the journal Nature Communications.

The liver has a remarkable ability to regenerate itself after damage or partial removal. However, it loses that ability in patients with alcohol-associated liver disease — the leading cause of liver-related mortality worldwide, resulting in roughly 3 million deaths annually.

The researchers compared samples of healthy livers and samples of livers with alcohol-associated hepatitis or cirrhosis obtained from Johns Hopkins University Hospital through an initiative supported by the National Institute for Alcohol Abuse and Alcoholism, part of the National Institutes of Health.

The first thing the researchers noticed in diseased livers was that, although damaged cells had begun the process of reverting to the regenerative state, they did not complete the process and instead remained in transitional limbo. The researchers found a possible driver of the RNA missplicing: Alcohol-damaged liver cells had a deficiency of the protein ESRP2, which binds to RNA to splice it properly.

To verify that ESRP2 deficiency was a likely culprit, the researchers studied mice without the gene that produces ESRP2. They displayed similar liver damage and regeneration failure to that seen in patients with advanced alcohol-related hepatitis. But why was ESRP2 missing from liver cells from patients with alcohol-related hepatitis? Upon investigation, the researchers found that liver support cells and immune cells, drawn to the liver tissue damaged by alcohol processing, released high amounts of inflammatory and growth factors. Those factors suppress ESRP2 production and activity.

To verify this finding, the researchers treated liver cell cultures with a molecule that inhibits the receptor for one of the inflammation-promoting factors. ESRP2 levels recovered and splicing activity was corrected, pointing to the pathway as a possible treatment target.