Researchers Uncover Two Distinct Types of Fatty Liver Disease

 

Researchers from Karolinska Institutet and the University of Gothenburg have identified two distinct forms of metabolic-associated fatty liver disease (MASLD): a liver-specific type and a systemic type that affects multiple organs. Published in two studies in Nature Medicine, this discovery offers hope for improved diagnosis and treatment for millions affected by this condition worldwide.

Understanding MASLD

MASLD, also known as metabolic dysfunction-associated steatotic liver disease, is characterized by excessive fat accumulation in the liver. It is primarily caused by obesity and overweight, making it a significant and growing global health burden. Alarmingly, one in four adults worldwide is estimated to have MASLD, yet most are unaware of their condition as symptoms typically appear only in advanced stages. Left untreated, MASLD can progress to severe complications such as cirrhosis, liver cancer, and organ failure.

Key Findings

By analyzing data from over 36,000 participants, including those in the UK Biobank, researchers identified two distinct subtypes of MASLD:

1. Liver-Specific Type: This aggressive form primarily affects the liver, leading to severe damage such as cirrhosis or cancer. Interestingly, it appears to protect against cardiovascular disease.
2. Systemic Type: This variant is closely tied to cardio-renal-metabolic syndrome and increases the risk of diabetes, heart disease, kidney failure, and other complications.

Using genetic analysis, the team identified 27 new genetic variants associated with MASLD. These discoveries enabled researchers to develop risk scores for the two types, helping to predict disease progression more accurately.

Advancing Precision Medicine

“This research helps us understand why some individuals develop severe liver disease while others suffer from cardio-renal complications,” explains Professor Stefano Romeo from Karolinska Institutet, who led the study. “By identifying these pathways, we can better predict disease trajectories and create personalized treatment plans.”

A complementary study, conducted in collaboration with Lille University in France, used a method called unsupervised clustering to achieve similar results. This clustering technique, based on simple clinical variables, helps distinguish patients at higher risk for cardiovascular diseases from those who are not.

Implications for Healthcare

The findings highlight the role of genetic research in tackling complex diseases like MASLD and advancing precision medicine. "This discovery represents a step forward in tailoring treatments to individual needs based on genetic and clinical data," Professor Romeo adds.

A simple calculator developed from the research can help clinicians predict the likelihood of MASLD progression and associated complications. Such tools are critical for early diagnosis, enabling healthcare providers to intervene before severe symptoms develop.

A Path to Better Treatment

MASLD’s widespread prevalence demands effective strategies for prevention and treatment. By uncovering its distinct subtypes, researchers have laid the groundwork for personalized therapies that target the specific mechanisms driving each type of the disease. This could revolutionize how MASLD is managed, shifting from a one-size-fits-all approach to precision medicine tailored to individual risk profiles.

Funding and Disclosures

The research was funded by organizations such as the Swedish Cancer Society, the Swedish Research Council, and the Knut and Alice Wallenberg Foundation. Professor Romeo disclosed consulting roles with AstraZeneca, Pfizer, and other pharmaceutical companies, alongside a research grant from AstraZeneca.

This groundbreaking work not only enhances understanding of MASLD but also underscores the importance of continued research into genetic and environmental factors affecting global health. By enabling earlier intervention and more effective treatments, it marks a significant step forward in addressing the global burden of fatty liver disease.