Scientists Discover 5 Subtypes of Fatty Liver Disease

A new study from Mayo Clinic researchers and collaborators at Virginia Tech suggests that metabolic dysfunction-associated steatotic liver disease (MASLD) may not represent one biologically uniform condition.

Researchers identified five distinct patient subgroups, each showing different clinical, genetic and disease-risk characteristics.

The findings were published in Nature Communications on September 2, 2026.

MASLD, formerly known as nonalcoholic fatty liver disease (NAFLD), occurs when excess fat accumulates in the liver in the setting of metabolic dysfunction. It has become one of the world's most common chronic liver diseases, affecting approximately 30% of adults globally.

Researchers found five different biological patterns

The researchers used clinical and genomic information from more than 4,600 people with MASLD.

Using computational modeling, they identified five subgroups with different combinations of metabolic, clinical and genetic characteristics. The findings were also reproduced in an independent patient cohort.

Among the groups were:

1. Non-obese cardiometabolic subtype

This group represents patients whose disease may occur without the typical picture of obesity.

2. Male-predominant cardiorenal subtype

This subgroup was associated with a higher prevalence of conditions including type 2 diabetes, obesity and sleep apnea.

3. Female-predominant obesity and mood-disorder subtype

Researchers identified a group characterized by obesity and mood disorders, with relatively high antidepressant use.

4. Polygenic MASLD subtype

This is particularly interesting because patients in this group had relatively fewer metabolic comorbidities but showed the highest rate of liver transplantation among the identified groups.

The researchers identified genetic contributions involving variants including TM6SF2, MBOAT7 and HSD17B13.

5. Another genetically and clinically distinct subtype

The fifth subgroup further demonstrates the biological heterogeneity of MASLD and supports the idea that apparently similar patients may have different underlying disease mechanisms.

Why genetics may matter

One of the most important findings is that significant liver disease risk may not always be obvious from traditional metabolic characteristics.

The researchers found genetic contributions across all five groups. In particular, the polygenic subgroup had a distinctive genetic profile associated with liver disease progression despite having fewer metabolic comorbidities.

This could eventually help clinicians identify patients who require closer monitoring even when their conventional metabolic risk profile does not appear particularly severe.

MASLD is more than a liver problem

The study also found associations between specific MASLD subgroups and conditions affecting other parts of the body, including:

Type 2 diabetes

Obesity

Sleep apnea

Cardiovascular disease

Kidney disease

Depression

Migraine

This supports the increasingly recognized view of MASLD as a systemic metabolic disease, rather than simply excess fat in the liver.

Could this lead to personalized liver treatment?

Potentially.

Today, MASLD is generally approached through assessment of metabolic risk, liver injury and fibrosis risk, followed by lifestyle and medical management where appropriate.

The new research raises the possibility of a future in which clinicians could classify patients according to their underlying biological subtype.

Instead of treating every MASLD patient as biologically similar, future care could potentially consider:

Genetics + metabolic profile + liver characteristics + comorbidities + disease trajectory

Researchers say they plan to investigate how the identified subtypes respond to different treatments, including GLP-1 receptor agonists, and to test the findings in broader populations.

What patients should know now

The discovery does not mean that there are currently five officially recognized types of fatty liver disease requiring five different treatments.

The five groups are research-defined biological subtypes that require further validation.

However, the findings reinforce an important principle:

Two people with fatty liver disease may not have the same underlying disease biology or the same future risk.

Anyone concerned about fatty liver disease should discuss appropriate assessment with a qualified healthcare professional rather than relying on symptoms alone.

MASLD can occur with few or no obvious symptoms, and assessment may involve medical history, metabolic measurements, liver enzymes, imaging and—when appropriate—additional fibrosis evaluation.

The bigger picture

The research represents another step toward precision medicine in hepatology.

As genomic data, electronic health records, imaging and artificial intelligence become increasingly integrated, researchers may be able to identify patients at higher risk of progression earlier and match monitoring and treatment more precisely to individual biology.

For a disease affecting roughly 30% of adults worldwide, understanding these differences could have major implications for future liver health.

Medical disclaimer

This article is for educational purposes only and does not replace medical diagnosis or treatment. If you have been diagnosed with fatty liver disease or have risk factors such as obesity, type 2 diabetes or abnormal liver tests, speak with a qualified healthcare professional about appropriate evaluation and follow-up.

Source: Priya TS et al., Nature Communications, 2026.