Researchers at the Karolinska Institutet and the University of Gothenburg have identified two types of metabolically related fatty liver disease – a liver-specific type and a systemic type that affects other organs and tissues. The discovery could lead to improved diagnosis and treatment of this growing group of patients. Two studies are published in sequence Nature Medicine.
Metabolic dysfunction-associated steatary liver disease (MASLD) is characterized by excessive accumulation of fat in the liver, which can lead to severe liver damage such as cirrhosis and liver cancer. MASLD is caused by overweight and obesity and is a significant and growing burden worldwide. It is estimated that one in four adults worldwide lives with MASLD, but most people are unaware of it because it only becomes symptomatic at an advanced stage.
Comprehensive analyses
Researchers at the Karolinska Institutet and the University of Gothenburg in Sweden have now identified two different types of MASLD by analyzing data from more than 36,000 participants from the UK Biobank and other studies.
“We discovered that there are at least two types of steatosis with different clinical trajectories,” says Stefano Romeo, Professor at the Huddinge Department of Medicine, Karolinska Institutet, who led the research. “One is more aggressive and mainly affects the liver, while the other is involved in cardiorenal-metabolic syndrome.”
Prediction of disease progression
The researchers used genetic tests to identify 27 new genetic variants linked to MASLD. By analyzing these genes, they were able to identify two different risk scores associated with the two types of MASLD. The liver-specific type is more aggressive and can lead to severe liver damage, but protects against cardiovascular disease, while the systemic type is associated with a higher risk of diabetes, cardiovascular disease, heart and kidney failure.
This discovery is important because it helps us understand why some people develop more severe liver disease while others suffer from cardiorenal disease. This will allow us to better predict the progression of these diseases and tailor treatment to the specific needs of the patient.”
Stefano Romeo, Professor at the Department of Medicine, Huddinge, Karolinska Institutet
Two parallel studies
A follow-up paper by Professor Stefano Romeo with researchers at the University of Lille in France showed similar results using another method, so-called unsupervised clustering.
“This work on clustering using simple clinical variables is of the utmost importance because it allows us to differentiate at an individual level who has MASLD and will develop CVD and who will not,” says Stefano Romeo.
Cluster prediction can be obtained using a simple calculator.
Advances in precision medicine
The study also highlights the importance of genetic research in understanding complex diseases such as MASLD and the mechanisms that cause cardiorenal-metabolic syndrome.
“This research is a step forward towards precision medicine, where treatments are tailored to fit individual needs based on genetic and clinical information,” says Stefano Romeo. “It may also raise awareness of how genetic and environmental factors affect our health and highlights the importance of continued research in this area.”
The research was mainly funded by the Swedish Cancer Society, the Swedish Research Council, ALF funds, the Swedish Heart-Lung Foundation, the Knut and Alice Wallenberg Foundation and the Novo Nordisk Foundation. The article lists several potential conflicts of interest. Stefano Romeo has consulted for AstraZeneca, GSK, Celgene Corporation, Ribo-cure AB and Pfizer over the past five years and has received a research grant from AstraZeneca.
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Journal Reference:
Jamialahmadi, O., et al. (2024). Distributed polygenic risk scores identify different types of steatotic liver disease associated with metabolic dysfunction. Nature Medicine. doi.org/10.1038/s41591-024-03284-0.
