Heavy drinkers who stop consuming alcohol may still not see their liver bounce back. A study led by the University of Illinois Urbana-Champaign has identified a molecular block that keeps damaged liver cells from regenerating, even after the last drink.
The team, working with Duke University and the Chan Zuckerberg Biohub Chicago, analyzed diseased human liver tissue from Johns Hopkins Hospital alongside mouse models and cell cultures. In alcohol-damaged livers, a protein called ESRP2, which helps cells process RNA correctly, was severely depleted.
The findings, published in Nature Communications, show that without enough ESRP2 thousands of genes are misspliced. Proteins the liver needs to rebuild itself lose the address labels that would send them to the nucleus, and pile up in the wrong part of the cell instead.
Cells suspended between two states
Under normal conditions, the liver can regrow. After injury, mature liver cells briefly shift into a progenitor-like state, multiply, and then return to their working form. In alcohol-damaged livers, that transition breaks.
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"They are neither functional adult cells nor proliferative progenitor cells. Since they are not functioning, more pressure builds on the remaining cells," said co-first authors Ullas Chembazhi and Sushant Bangru, graduate students at the University of Illinois, describing the research reported by the university.
"In comparing the samples, we saw RNA was getting misspliced broadly in alcohol-related liver disease, across thousands of genes, and it was affecting major functions of proteins," said Auinash Kalsotra, a biochemistry professor at the University of Illinois and senior author of the study.
Who is most at risk
The mechanism was strongest in patients with severe alcoholic hepatitis and cirrhosis, forms of alcohol-associated liver disease in which the organ is heavily scarred and inflamed.
Inflammation from surrounding immune and support cells appeared to be what shuts down ESRP2 in the first place. When the researchers blocked those inflammatory signals in cell cultures, ESRP2 levels rebounded and splicing began to work again.
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Quitting drinking still helps many patients. An international study of 633 people with alcohol-related cirrhosis, published in the Journal of Hepatology in January 2026, found that about one in three patients with already advanced disease saw all their liver complications resolve within five years of sustained abstinence.
The Illinois-led work helps explain why some do not, and points to inflammation and RNA splicing as possible future drug targets.
What it means in practice
No approved medication yet restores ESRP2 or corrects the splicing errors it controls, so the current tools remain abstinence, close monitoring and treatment of complications.
Anyone who has been drinking heavily and notices yellowing of the skin or eyes, abdominal swelling, ongoing fatigue or unexplained weight loss should be evaluated by a doctor, since blood tests and imaging can pick up damage that will not reverse on its own.
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Some of the changes the body goes through after quitting alcohol unfold quickly, but full liver repair is not one of them for people already at an advanced stage.
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This article is made and published by Jesper Bengtson, who may have used AI in the preparation.