TGen study finds liver disease genetic drivers

The announcement noted that MASLD was previously known as non-alcoholic fatty liver disease. MASH is a more severe form of the same disease, leading to higher risks of conditions such as fibrosis, cirrhosis and hepatocellular carcinoma.

MASLD, it said, currently affects about 30% of people across the world, and that total is expected to almost double by 2040.

“The absence of pharmacological interventions for MASH until the recent FDA approval in March 2024 underscores the urgent need addressed by this research,” the announcement stated.

A report from TGen researchers Johanna K. DiStefano, Ph.D., and Ignazio S. Piras, Ph.D., was published in Life Science Alliance on April 2. Their study, which the announcement said was the largest of its kind, analyzed information about liver gene expression from 1,058 patients to learn about the molecular drivers of MASLD.

“Given the complex nature of MASLD, which is influenced by diverse genetic, lifestyle, demographic and environmental factors, we would expect many genes across a number of different pathways to be involved,” DiStefano said. “However, our investigation is the first to look at drivers of this disease progression from this unique perspective."

The study compared over 12,000 shared genes, and Piras explained in the announcement that using multiple datasets gave a “more robust perspective of gene expressions [than] from the individual studies alone, which are more prone to false positive and negative results.”

The researchers identified two gene networks co-expressed in MASLD -- one of which had not previously been connected to the disease -- and found that differences in gene expression between MASLD and MASH “were even larger than those between [either disease] and healthy liver tissue.”

"Based on our rigorous statistical analysis, these are genes that are great candidates for driving disease progression, and they highlight promising candidates for targeted interventions, opening the door for the development of new treatments to prevent MASH," DiStefano said.

The study was funded through a National Institute of Diabetes and Digestive and Kidney Diseases grant. The report is available online, with more about TGen at tgen.org.