Liver Health: Liver sometimes can’t fix itself, even after you quit alcohol: Scientists explain why heavy drinking stops the liver from healing |

Long-term heavy drinking can seriously damage your liver, but new research is shedding light on why the liver sometimes can’t repair itself, even after someone quits alcohol. Scientists from the University of Illinois Urbana-Champaign, Duke University, and the Chan Zuckerberg Biohub Chicago have uncovered crucial details about alcohol-related liver disease (ARLD)—insights that could lead to new treatments beyond liver transplants.

Alcohol puts liver cells in “limbo”

The liver is unique—it can regenerate. If part of it is removed or injured, healthy liver cells multiply to rebuild the tissue. This ability is why liver transplants can succeed and why organs like the heart don’t recover the same way.But here’s the catch: years of heavy drinking can rob the liver of this regenerative power. People with alcohol-related hepatitis or advanced cirrhosis develop scarring and liver failure, and sadly, stopping drinking doesn’t always reverse the damage.Researchers compared healthy livers with those affected by alcohol damage. They found that liver cells try to switch into repair mode, but get stuck in a half-functioning state.They’re not fully mature liver cells.They aren’t becoming the “stem-like” cells needed to regrow tissue.It’s like being halfway up a ladder—unable to climb up or down. These semi-functional cells add pressure on the remaining healthy cells, causing the liver’s repair system to falter.

RNA splicing problems

Every cell uses RNA as instructions to make proteins. In damaged livers, RNA splicing—the process that edits these instructions—is broken. Think of it like trying to edit a movie but putting all the scenes out of order. The result? Proteins that don’t work in the right place, and liver repair grinds to a halt.The study identified ESRP2, a protein that helps with RNA splicing, as missing in damaged liver cells. Without ESRP2, the liver’s “repair instructions” fail, stopping regeneration.To confirm this, researchers studied mice without ESRP2 and found the same type of liver damage seen in humans with alcohol-related liver disease.

Inflammation makes it even worse

Alcohol-damaged livers become inflamed. Immune and support cells flood the liver with chemicals that suppress ESRP2, compounding the problem. In lab experiments, blocking one of these inflammatory pathways restored ESRP2 levels and fixed RNA splicing, showing a promising path for treatment.“We knew that the liver stops functioning and stops regenerating in patients with alcohol-related hepatitis and cirrhosis, even when a patient has discontinued consuming alcohol, but we didn’t know why,” said U. of I. biochemistry professor Auinash Kalsotra, who co-led the study with Duke University School of Medicine professor Anna Mae Diehl. “The only real life-saving treatment option once a patient reaches the liver failure stage in those diseases is transplantation. But if we understood why these livers were failing, maybe we could intervene.”

What this could mean for the future

This research opens doors for new therapies for alcohol-related liver disease. Future treatments might:

For millions of Americans affected by alcoholic liver disease, these findings could lead to life-saving alternatives to liver transplants.