Oct. 9, 2025 – Alcohol, medications, even junk food – we challenge our liver every day. Usually, it bounces back thanks to its remarkable ability to repair itself.
The problem: If you drink too much for too long, the liver can lose that regenerative power.
"One fine day, the liver says, 'I am done. I don't want to do this anymore.' And it gives up and goes into what we call a 'decompensated state,' " meaning it no longer regenerates, said Auinash Kalsotra, PhD, a University of Illinois professor and an expert in liver biochemistry.
Scientists have long known this tipping point exists – but not why. Now a group of scientists, led by Kalsotra, have discovered what goes wrong inside liver cells when alcohol-related damage can't be reversed.
The findings offer fresh clues for managing liver health if you drink – and bring us a step closer to new treatments for people with life-threatening liver disease, even those who aren't eligible for a transplant.
Why the Liver Stops Repairing Itself
Healthy liver cells can shift between two operating states: adult mode and fetal mode. In adult mode, cells carry out daily jobs such as processing nutrients and clearing toxins. And fetal mode is when the liver makes new cells to replace damaged ones.
After comparing healthy livers to diseased samples, the researchers found that in cases of alcohol-associated hepatitis (a dangerous inflammatory flare-up) and cirrhosis (scarring from years of heavy drinking), the genetic instructions that allow cells to switch states – a process called RNA splicing – become scrambled. Instead of moving cleanly from adult to fetal mode, the cells get stuck in an in-between state, unable to fully regenerate or carry out their routine functions.
The good news is that a type of therapy that restores normal RNA function already exists. It treats spinal muscular atrophy, a rare condition that weakens voluntary muscles. Kalsotra's team is now exploring whether a similar approach could restart the repair process in damaged livers.
How to Monitor Your Liver's Health
Most liver health advice boils down to vague strategies like drink "moderately," eat a healthy diet, exercise, and maintain a healthy weight, blood pressure, cholesterol, and blood sugar. That's all true – but you can also take concrete steps to understand your personal risk.
"The liver has hundreds of functions in the body and key roles in everything from digestion to the immune system, waste management, and blood clotting," said Hannes Hagström, MD, PhD, a professor at the Karolinska Institute in Stockholm, Sweden, who recently developed a way for doctors to estimate a person's 10-year risk of developing liver disease. "If you take care of your liver, your liver takes care of you."
Standard tips often seem vague because many personal factors combine over time to affect liver health. The best way to get an idea of what's happening inside your liver is to schedule routine blood tests – specifically, a liver function panel, which can be done during annual physicals. Hagström's 10-year risk model uses three common markers in that panel – GGT (gamma-glutamyl transferase), AST (aspartate aminotransferase), and ALT (alanine aminotransferase). (On the horizon: Kalsotra's discoveries could one day lead to a blood test that shows when the liver is approaching the "regeneration limbo" stage, offering a chance to intervene earlier.)
Your personal history matters, too – how much you drink, how often, and even periods of heavy drinking in the past. Online questionnaires, often used in clinics, can help identify whether your past or current habits put you at higher risk.
"Most patients we see with end-stage liver disease found out too late that they had a sick liver," Hagström said. If you're concerned about liver disease, he recommends making a plan with your doctor to do regular, repeat testing so you can spot potential red flags early.
Helping Your Liver Heal
National guidelines for moderate drinking recommend a limit of one drink a day for women and two for men. But more and more research is showing that even moderate alcohol use raises health risks, including the risks of early death and cancer.
Is quitting drinking the only option to reduce risk? It definitely helps, Kalsotra said – even if you abstain for days or months at a time.
Another way to help your liver is to focus on reducing inflammation, Kalsotra said. In lab experiments, when the team blocked inflammation in liver cells that were stuck in limbo, the cells started working properly again. "We were very excited by that," he said, adding that diet is a powerful way to reduce liver inflammation.
