Cholesterol Crystals May Trigger Some Liver Disease

New research from the University of Pennsylvania finds cholesterol crystals in the liver may stiffen the organ early in metabolic dysfunction-associated steatotic liver disease.

Published on Feb. 12, 2026

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Researchers at the University of Pennsylvania have found that cholesterol crystals in the liver may stiffen the organ early in those with metabolic dysfunction-associated steatotic liver disease (MASLD), even before scarring develops. The findings suggest detecting these cholesterol crystals could help identify patients at highest risk for severe liver disease and allow for earlier intervention.

Why it matters

MASLD, where excess fat builds up in the liver, is a growing concern with estimates suggesting 122 million US adults could have the condition by 2050. In some cases, MASLD can lead to liver transplants or cancer. This new research provides insights into how cholesterol crystals may contribute to liver stiffening and scarring, potentially enabling earlier diagnosis and treatment.

The details

In experiments, rats fed high-fat, high-cholesterol diets developed cholesterol crystals in their livers and had stiffer liver tissue compared to rats just on high-fat diets. The researchers were able to reverse the liver stiffening by removing the cholesterol crystals, though this method is not applicable to humans. A key challenge is that cholesterol crystals can only be measured through an invasive liver biopsy, so developing a non-invasive way to detect crystal buildup could be important for identifying high-risk MASLD patients.

  • The study findings were published in Proceedings of the National Academy of Sciences on February 12, 2026.

The players

Rebecca G. Wells

A professor of Gastroenterology and Hepatology at the University of Pennsylvania and the senior study author.

Perelman School of Medicine at the University of Pennsylvania

The institution where the research was conducted.

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What they’re saying

“Predicting liver health, particularly among those who have MASLD, has been a major challenge for clinicians because about a third of the world's population has significant amounts of fat in the liver, but only a small percentage go on to have more serious disease. Our findings suggest that detecting cholesterol crystals in the liver, and creating an easy way to do so, could help identify those patients at highest risk for severe liver disease. That would allow clinicians to intervene earlier by encouraging healthy eating habits or monitoring them more closely and providing treatment before serious damage occurs.”

— Rebecca G. Wells, Professor of Gastroenterology and Hepatology (Mirage News)

What’s next

Researchers hope to learn if readily accessible medications like statins, which reduce cholesterol in the blood, have potential to help treat cholesterol crystals in the liver.

The takeaway

This research provides new insights into how cholesterol crystals may contribute to the progression of metabolic dysfunction-associated steatotic liver disease, a growing public health concern. Developing non-invasive methods to detect these crystals could enable earlier intervention and treatment for high-risk patients.