Alcohol & Liver Healing: Why It’s Hard to Recover
- 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, researchers...
- 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...
- The liver has a remarkable ability to regenerate itself after damage or partial removal.
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Alcohol’s Impact on Liver Regeneration: A New Understanding
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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, researchers at University of Illinois urbana-Champaign and collaborators at Duke University and the Chan Zuckerberg Biohub Chicago describe in a new study.
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.
What is alcohol-associated Liver Disease?
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. This disease encompasses a spectrum of conditions, from alcoholic fatty liver disease to alcoholic hepatitis and cirrhosis.
Alcoholic Fatty liver Disease: The earliest stage, often reversible with abstinence. Characterized by a buildup of fat in the liver.
Alcoholic Hepatitis: Inflammation of the liver, perhaps life-threatening.Symptoms can range from mild to severe.
Cirrhosis: Severe scarring of the liver, irreversible and can lead to liver failure.
The Research Findings: A Deep Dive
“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.”
Both the Kalsotra and Diehl labs have studied the molecular and cellular underpinnings of liver regeneration. Over the last five years, they found that to regenerate, liver cells reprogram their gene expression to revert to fetal-like progenitor cells, multiply and then reverse the process back to become mature functioning cells again. Armed with this knowledge, the group turned to the question of how those mechanisms were disrupted in alcohol-associated liver disease.
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.
“They are neither functional adult cells nor proliferative progenitor cells. Since they are not functioning, more pressure builds on the remaining cells.