Researchers have shown that cholesterol crystals in the liver may lead to hardening at an early stage in people with metabolic disorder-associated fatty liver disease (MASLD), long before scarring appears.
These findings may help explain why this type of liver disease is exacerbated by high cholesterol, and open up new opportunities for early diagnosis and treatment.
Dr. Rebecca G. Wells, Professor of Gastroenterology and Hepatology and lead author of the study, said: "Predicting liver health, especially in those with metabolic fatty liver disease, has always been a major challenge for physicians, as about a third of the world's population has fat accumulation in the liver, but only a small percentage of them develop serious liver disease."
She added that detecting cholesterol crystals and developing an easy way to detect them could help doctors identify patients most at risk of developing acute liver disease, allowing for early intervention by encouraging healthy eating habits or monitoring patients and providing treatment before serious damage occurs.
MASLD occurs when excess fat accumulates in the liver. In some cases, patients may require a liver transplant or develop liver cancer. Fat accumulation is associated with obesity, insulin resistance, and type 2 dia betes, and is often linked to malnutrition, while genetic predisposition plays a role in some individuals.
In the lab, a research team from the Perelman School of Medicine at the University of Pennsylvania gave mice either a diet high in fat and cholesterol or a diet high in fat alone. Both diets resulted in fatty liver disease, meaning fat accumulates in liver cells. However, the mice fed the high-fat, high-cholesterol diet developed crystals in their livers, and their livers were firmer than those of the other mice. Notably, the crystals could only be measured via surgical biopsy.
Cholesterol crystals and potential treatments
The study showed that cholesterol crystals harden liver tissue and create an environment conducive to further scarring. Researchers were able to reverse liver hardening by removing the crystals in mice, although the method has not yet been applied to humans.
There are still challenges to clinical application, as crystals can only be measured by biopsy, which necessitates the development of an accurate and non-invasive method to identify patients most at risk of liver damage.
Although statins are known for their ability to lower blood cholesterol, researchers hope that these drugs or other available interventions will help treat cholesterol crystals in the liver in the future.
The study was published in the Proceedings of the National Academy of Sciences.
