What Is Fatty Liver?
Fatty liver refers to an excessive accumulation of fat in the liver.
The terminology has changed in recent years. Metabolic dysfunction-associated steatotic liver disease (MASLD) is now used for fatty liver disease associated with metabolic dysfunction.
A more active form is called metabolic dysfunction-associated steatohepatitis (MASH).
MASH involves:
- Fat accumulation
- Liver-cell injury
- Inflammation
- Fibrosis, or liver scarring
Fibrosis is particularly important because increasing amounts of liver scarring are associated with a higher risk of serious liver complications.
The ESSENCE trial specifically studied patients with biopsy-confirmed MASH and stage 2 or stage 3 fibrosis.
Why MASH Matters
Fatty liver can exist without obvious symptoms. A person may feel completely well while changes are occurring inside the liver.
For some patients, MASH can gradually progress to more significant fibrosis. Advanced fibrosis is associated with a higher risk of liver-related complications and mortality.
MASH is also closely connected with cardiovascular and metabolic health. Patients may have several conditions at the same time, including:
- Obesity
- Type 2 diabetes
- Insulin resistance
- High cholesterol
- High blood pressure
- Cardiovascular disease
This means liver health cannot always be considered separately from weight and metabolic health.
Why Fatty Liver and Metabolic Health Are Connected
The liver plays a central role in managing energy, fats, and blood sugar.
When the body develops metabolic dysfunction, excess fat can accumulate in the liver. Insulin resistance can also contribute to changes in how the body stores and processes fat.
This means fatty liver is often not an isolated liver problem.
Patients with MASLD or MASH may also have:
- Obesity
- Insulin resistance
- Prediabetes
- Type 2 diabetes
- High triglycerides
- Abnormal cholesterol
- High blood pressure
In the ESSENCE trial, 55.9% of participants had type 2 diabetes and 72.8% met the study’s definition of obesity.
This illustrates how frequently metabolic conditions can occur alongside MASH.
What Is Insulin Resistance?
Insulin is a hormone that helps move glucose from the bloodstream into cells, where it can be used for energy.
Insulin resistance occurs when the body’s cells respond less effectively to insulin. The body may compensate by producing more insulin, while blood glucose can gradually become harder to control.
Insulin resistance is closely associated with obesity and type 2 diabetes and is also involved in the development of metabolic liver disease.
The ESSENCE researchers described metabolic dysfunction as an important driver of the processes that can lead to liver fat accumulation, inflammation, and fibrosis.
Why Weight Management Can Matter for Liver Health
Weight management is often discussed in terms of appearance or body weight, but its importance extends to metabolic health.
Reducing excess body weight may help improve:
- Blood sugar regulation
- Insulin sensitivity
- Blood pressure
- Cholesterol and triglycerides
- Abdominal fat
- Metabolic inflammation
In the ESSENCE trial, patients receiving semaglutide experienced greater weight reduction than those receiving placebo.
At week 72:
- Mean weight change was −10.5% with semaglutide
- Mean weight change was −2.0% with placebo
Weight loss was one part of the overall metabolic changes observed during the study.
What Did the ESSENCE Trial Study?
ESSENCE is an ongoing phase 3 clinical trial investigating semaglutide in patients with MASH.
The trial enrolled 1,197 patients overall.
The interim analysis published in 2025 included the first 800 patients who had completed 72 weeks:
- 534 received semaglutide 2.4 mg
- 266 received placebo
Participants had biopsy-confirmed MASH and stage 2 or stage 3 liver fibrosis.
The trial is continuing for a total planned follow-up of 240 weeks, with later analysis intended to evaluate clinical outcomes including cirrhosis-free survival.
What Did Researchers Find About Liver Inflammation?
One of the main findings was an improvement in steatohepatitis.
After 72 weeks, resolution of steatohepatitis without worsening of liver fibrosis occurred in:
- 62.9% of patients receiving semaglutide
- 34.3% receiving placebo
The estimated difference was 28.7 percentage points.
This suggests that more patients receiving semaglutide showed resolution of the inflammatory component of MASH without their fibrosis becoming worse.
However, this does not mean that semaglutide has been proven to prevent cirrhosis or liver failure. Those longer-term clinical outcomes are still being studied.
What Did Researchers Find About Liver Fibrosis?
Fibrosis is the formation of scar tissue within the liver.
The second primary endpoint looked at a reduction in fibrosis without worsening of steatohepatitis.
After 72 weeks:
- 36.8% of patients receiving semaglutide achieved fibrosis reduction
- 22.4% of patients receiving placebo achieved fibrosis reduction
The estimated difference was 14.4 percentage points.
The trial also found that 32.7% of participants receiving semaglutide achieved both MASH resolution and fibrosis reduction, compared with 16.1% receiving placebo.
These findings are clinically interesting because fibrosis stage is an important indicator of long-term liver risk.
What Happened to Insulin Resistance and Blood Sugar?
The researchers also observed improvements in metabolic markers.
Semaglutide was associated with improvements in:
- Glycaemic control
- Insulin resistance
- Blood pressure
- Triglycerides
- Cholesterol
- High-sensitivity C-reactive protein
At week 72, HbA1c decreased by:
- 0.42 percentage points among participants without type 2 diabetes
- 1.08 percentage points among participants with type 2 diabetes
The placebo group showed much smaller changes.
These results reinforce the close relationship between metabolic health and liver disease.
What About Liver Blood Tests?
Liver enzymes such as ALT and AST are commonly measured as part of a medical evaluation.
In the ESSENCE trial, reductions in aminotransferase levels were observed relatively early, with changes apparent by 12 weeks.
The study also reported improvements in several non-invasive measures associated with liver health, including:
- Enhanced Liver Fibrosis (ELF) score
- Liver stiffness
- FibroScan-AST (FAST) score
- PRO-C3
- Gamma-glutamyltransferase
At week 72, 55.8% of patients receiving semaglutide had a decrease in ELF score of at least 0.5, compared with 25.5% receiving placebo.
However, liver enzymes alone cannot determine whether someone has advanced fibrosis. Additional assessment may be necessary.
Who May Benefit From a Metabolic and Liver Health Check?
A liver and metabolic assessment may be particularly useful if you have risk factors for fatty liver disease.
These may include:
- Overweight or obesity
- Prediabetes
- Type 2 diabetes
- Insulin resistance
- High triglycerides
- Abnormal cholesterol
- High blood pressure
- Increasing waist circumference
- Previously diagnosed fatty liver
- Abnormal liver enzymes
You do not necessarily need symptoms to have fatty liver or metabolic dysfunction.
When Should You Consider Checking Your Liver Health?
Consider speaking with a doctor if you have been told that you have fatty liver, have persistently abnormal liver enzymes, or have several metabolic risk factors.
A doctor may recommend blood tests such as:
- ALT
- AST
- GGT
- HbA1c
- Fasting glucose
- Lipid profile
Depending on your risk profile, additional assessment such as ultrasound or non-invasive fibrosis testing may also be considered.
Patients with suspected advanced fibrosis may require specialist evaluation.
What a Doctor May Assess
A doctor-led approach may include:
- Medical consultation
- Weight and BMI assessment
- Waist circumference
- Blood pressure
- Medical history
- Family history
- Alcohol intake
- Liver function tests
- HbA1c and blood glucose
- Cholesterol and triglycerides
- Insulin resistance risk
- Fibrosis risk assessment
- Liver imaging if appropriate
- Current medication review
- Weight-management options
- Follow-up guidance
The goal is to understand the relationship between your liver and overall metabolic health.
Benefits and Key Points to Understand
The ESSENCE trial provides important evidence about the relationship between MASH, weight, and metabolic health.
Key points include:
- Fatty liver is closely connected with metabolic dysfunction
- MASH involves inflammation and liver-cell injury
- Fibrosis represents liver scarring
- Obesity and type 2 diabetes commonly coexist with MASH
- Weight loss may improve several metabolic factors
- Semaglutide was associated with improvements in MASH and fibrosis in the study population
- Long-term clinical outcomes from the ongoing trial are not yet available
Managing liver health should therefore involve more than looking at liver enzymes alone.
Safety, Side Effects, and Important Considerations
Semaglutide was generally consistent with its established safety profile in the ESSENCE trial.
Gastrointestinal symptoms were the most common adverse events.
Among participants receiving semaglutide:
- Nausea occurred in 36.2%
- Diarrhoea occurred in 26.9%
- Constipation occurred in 22.2%
- Vomiting occurred in 18.6%
The corresponding rates were lower in the placebo group.
Serious adverse events occurred in 13.4% of participants in both groups, while treatment discontinuation due to adverse events occurred in 2.6% of the semaglutide group and 3.3% of the placebo group.
Patients with liver disease should discuss their full medical history and current medications with a doctor before starting or changing treatment.
Important Limitations of the Research
The ESSENCE results are promising, but they should be interpreted carefully.
The published findings are from an interim 72-week analysis, not the final results of the trial.
The study is still ongoing, with a planned 240-week follow-up designed to evaluate longer-term clinical outcomes.
The study population also consisted specifically of patients with biopsy-confirmed MASH and stage 2 or 3 fibrosis. The findings should therefore not automatically be applied to everyone with mild fatty liver.
The study was funded by Novo Nordisk, and several authors were employees or reported financial relationships with pharmaceutical companies.
Why Doctor-Led Care Matters
Fatty liver is not one single condition. The severity can range from simple fat accumulation to active inflammation and significant fibrosis.
A person may have fatty liver with relatively normal blood tests, while another person may have substantial fibrosis requiring closer monitoring.
This is why treatment decisions should consider:
- Liver health
- Metabolic health
- Weight
- Blood sugar
- Cholesterol
- Blood pressure
- Fibrosis risk
- Current medication
- Lifestyle factors
A doctor can help determine which tests are appropriate and whether weight management should be part of the overall treatment strategy.
Book a Liver and Metabolic Health Consultation in Bangkok
If you have been diagnosed with fatty liver, have abnormal liver tests, or are concerned about weight and metabolic health, a medical assessment can help clarify your individual risk.
MedConsult Clinic provides doctor-led consultations in Bangkok, with health assessments and blood testing where appropriate.
Understanding your metabolic and liver health together can provide a more complete picture than looking at body weight or a single blood test alone.
Frequently Asked Questions
Is fatty liver linked to insulin resistance?
Yes. Fatty liver and insulin resistance are closely associated with metabolic dysfunction, obesity, and type 2 diabetes.
Can losing weight improve fatty liver?
Weight loss can improve several metabolic factors associated with fatty liver. The extent of liver improvement depends on the type and severity of liver disease.
What is the difference between MASLD and MASH?
MASLD refers to metabolic dysfunction-associated steatotic liver disease. MASH is a more active form involving liver-cell injury and inflammation.
Can blood tests show liver fibrosis?
Blood tests can help estimate fibrosis risk, but they cannot always determine the stage of liver scarring. Doctors may use additional non-invasive tests or imaging when appropriate.
Does everyone with fatty liver need medication?
No. Treatment depends on the severity of liver disease, metabolic health, other medical conditions, and individual risk factors.
References
Sanyal AJ, Newsome PN, Kliers I, et al.
https://doi.org/10.1056/NEJMoa2413258
Rinella ME, Lazarus JV, Ratziu V, et al.
European Association for the Study of the Liver, European Association for the Study of Diabetes, European Association for the Study of Obesity.
Rinella ME, Neuschwander-Tetri BA, Siddiqui MS, et al.
Phase 3 Trial of Semaglutide in Metabolic Dysfunction–Associated Steatohepatitis. New England Journal of Medicine. 2025;392:2089–2099.
A multisociety Delphi consensus statement on new fatty liver disease nomenclature. Journal of Hepatology. 2023;79:1542–1556.
Clinical Practice Guidelines on the management of metabolic dysfunction-associated steatotic liver disease. Diabetologia. 2024;67:2375–2392.
AASLD Practice Guidance on the clinical assessment and management of nonalcoholic fatty liver disease. Hepatology. 2023;77:1797–1835.