The findings, published in Nature Communications, come from researchers at Mayo Clinic in the United States and Virginia Tech.
The study suggests that the disease can develop through different biological pathways, with each subtype carrying distinct health risks.
Some forms are closely associated with obesity and type 2 diabetes, while others are linked to inherited genetic differences.
Researchers found that certain genetic subtypes were associated with a higher risk of advanced liver damage, including among people without typical metabolic risk factors.
The discovery could help doctors identify vulnerable patients earlier and improve screening and treatment strategies.
To identify the subtypes, researchers analysed genetic sequencing results and medical records from more than 4,600 patients diagnosed with MASLD.
The information included liver enzyme levels, body mass index, blood lipid measurements and other indicators of metabolic health.
Researchers also examined conditions such as diabetes, depression and sleep apnoea.
Using computer models, the team identified five groups with distinct genetic and clinical characteristics.
The findings suggest that patients who receive the same diagnosis may experience different patterns of disease progression and face different risks of complications.
MASLD develops when excess fat accumulates in the liver. Although many patients experience no noticeable symptoms, the condition can progress to inflammation, scarring and cirrhosis, which can impair liver function. Severe cases may lead to liver failure, cancer or the need for a transplant.
The study also identified associations between particular disease subtypes and conditions such as depression, sleep apnoea and migraines.
However, the findings do not establish that MASLD directly causes these conditions.
The researchers used Mayo Clinic’s Research Data Atlas, which links genetic information with medical records, to identify patterns that might otherwise remain undetected.
The analysis also drew on genetic resources from the institution’s Tapestry Study, involving more than 100,000 participants.
The team plans to validate the findings in larger and more diverse populations and investigate whether the subtypes respond differently to available treatments, including GLP-1 receptor agonists, medicines used for conditions such as type 2 diabetes and obesity.
Researchers say the findings could eventually support earlier intervention and treatments tailored to patients’ underlying biology.
However, further studies are needed before the five-subtype classification can be routinely used in clinical practice.
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