Researchers from the Mayo Clinic and Virginia Tech have identified five distinct biological subtypes of metabolic dysfunction-associated steatotic liver disease (MASLD), challenging the long-held view that the condition is a single illness. This discovery, published in Nature Communications, redefines a disease affecting nearly 30% of adults worldwide.

This finding is significant because each of these five subtypes carries different risks for serious health complications, including heart disease, liver failure, cancer, and the need for liver transplantation. Recognizing these distinctions could lead to more precise screening, earlier identification of high-risk patients, and personalized treatment strategies for millions of people.

What the records show

The study, conducted by researchers from the Mayo Clinic and Virginia Tech, analyzed genetic and detailed clinical data from over 4,600 patients with MASLD. Before this research, MASLD, formerly known as nonalcoholic fatty liver disease, was generally treated as a single condition marked by fat accumulation in the liver. The research now shows that MASLD develops through multiple biological pathways. Some subtypes are strongly influenced by inherited genetic factors and can lead to advanced liver disease even in patients without typical metabolic risk factors like obesity or diabetes. Other subtypes are more closely tied to metabolic issues. The study also revealed associations between certain MASLD subtypes and conditions such as depression, sleep apnea, and migraine. Shulan Tian, a bioinformatician at Mayo Clinic and co-senior author of the study, stated that analyzing clinical and genomic data at this scale reveals "patterns of disease progression that would otherwise remain hidden".

What changed and for whom

For patients diagnosed with MASLD, this reclassification means the potential for more targeted care. The traditional approach treated MASLD as a uniform condition, but the new understanding suggests that different biological drivers necessitate different diagnostic and therapeutic approaches. Identifying these subtypes can help clinicians to more accurately predict a patient's risk of disease progression, including to cirrhosis, liver cancer, or the need for a liver transplant. Personalized treatment based on a specific subtype could lead to more effective interventions and improved patient outcomes.

What the subject has said publicly

Shulan Tian, co-senior author and a bioinformatician at Mayo Clinic, noted that once these subtypes are separated, medical professionals "can start to match treatments to the biology that's actually driving the disease".

What we could not confirm

The study does not detail the specific names or identifying characteristics of each of the five subtypes. The long-term efficacy of subtype-specific treatments has not yet been established.