Metabolic Dysfunction–Associated Steatotic Liver Disease (MASLD)
Information on the causes, symptoms, and treatments for fat accumulation in the liver.
Symptoms and Causes
Metabolic dysfunction–associated steatotic liver disease (MASLD) is a condition that causes pathological accumulation of fat in the liver as a result of obesity and insulin resistance.
Some time ago, this condition was referred to as hepatic steatosis or nonalcoholic fatty liver disease and was considered a benign disorder. However, studies revealed that it is caused by profound metabolic dysfunction whose progression may lead to serious diseases. For this reason, its nomenclature was changed to MASLD to better reflect its underlying pathophysiology. Even so, when detected early, when it is not associated with other diseases, and when medical recommendations are followed, the prognosis is good.
As a consequence of the rising prevalence of obesity and type 2 diabetes, MASLD is currently the most common liver disease. It is estimated to affect 5% of the global population (between 1.5% and 6.5% in Spain), and its prevalence is expected to increase by 56% by 2030 compared with 2016.
Symptoms
In the early stages, metabolic dysfunction–associated steatotic liver disease may be asymptomatic. As it progresses, the following symptoms may occur:
- Chronic fatigue: may become very intense as the disease advances.
- Hepatomegaly: enlargement of the liver due to fat accumulation or inflammation. This condition may cause a sensation of fullness or pain on palpation.
- Pain in the upper right abdomen: usually a consequence of hepatomegaly or inflammation of Glisson’s capsule, the fibrous tissue that surrounds the liver.
- General malaise.
- Jaundice: yellow discoloration of the skin, eyes, and mucous membranes, indicating advanced disease, caused by bilirubin accumulation in the blood due to impaired liver function.
- Generalized pruritus: in more severe cases, liver failure leads to toxin accumulation in the skin, resulting in itching.
Causes
MASLD results from a combination of genetic and environmental factors:
- Metabolic dysfunction, primarily insulin resistance.
- High intake of sugars and fats.
Contrary to common belief, metabolic dysfunction–associated steatotic liver disease is not related to excessive alcohol consumption.
Risk factors
The risk of MASLD is higher in the following situations:
- Sedentary lifestyle, as it promotes overweight.
- Obesity, particularly abdominal obesity.
- Type 2 diabetes.
- Metabolic syndrome: a cluster of disorders that, when present together, increase the likelihood of developing cardiovascular disease, stroke, or type 2 diabetes.
- Arterial hypertension.
- Dyslipidemia (hypercholesterolemia and elevated blood triglyceride levels).
- Genetic predisposition: the disease has been associated with abnormalities in the PNPLA3 gene, which is involved in hepatic lipid metabolism.
Complications
Complications of metabolic dysfunction–associated steatotic liver disease can be very serious. The most significant include:
- Hepatic inflammation.
- Progressive liver fibrosis: gradual scarring of liver tissue.
- Liver cirrhosis: the most advanced stage of fibrosis, characterized by accumulation of scar tissue forming regenerative nodules that distort hepatic architecture.
- Hepatocellular carcinoma: the most common type of liver cancer.
- Metabolic dysfunction–associated steatohepatitis (MASH): MASLD accompanied by hepatic inflammation and fibrosis.
- Liver failure.
Prevention
MASLD can be prevented by adopting a healthy lifestyle:
- Maintaining an appropriate body weight.
- Engaging in regular physical activity.
- Following a balanced diet rich in fruits and vegetables and low in fats and foods with added sugars.
- Consuming foods with low salt content.
- Adequately controlling chronic diseases such as diabetes or hypertension.
Which physician treats MASLD?
Metabolic dysfunction–associated steatotic liver disease is diagnosed and treated within the specialty of gastroenterology (digestive system), although endocrinology and nutrition are also frequently involved.
Diagnosis
Diagnosis of metabolic dysfunction–associated steatotic liver disease is based on biomarker analysis and the use of advanced technology, primarily to differentiate MASLD from MASH. The most commonly performed tests when this disease is suspected include:
- Blood tests: provide information on levels of liver enzymes (ALT, AST, GGT, alkaline phosphatase) and albumin in the bloodstream. Elevated levels may indicate liver disease.
- Ultrasound: uses sound waves to obtain images of the liver. It is useful for detecting fat accumulation and assessing liver size.
- Computed tomography (CT): uses X-rays from different angles to obtain a detailed three-dimensional representation of the liver, allowing detection of fat accumulation when ultrasound findings are inconclusive.
- Elastography: measures liver stiffness and therefore assesses fibrosis. It can be performed using two methods:
- Ultrasound-based elastography: a transducer emits low-frequency waves and measures their propagation speed through tissues.
- Magnetic resonance elastography: while magnetic resonance images are obtained, vibrations are applied to evaluate liver stiffness.
- Biopsy: a sample of liver tissue is obtained and examined under a microscope to detect fat accumulation, inflammatory tissue, or cellular necrosis.
Treatment
The first step in treating MASLD is dietary modification (a Mediterranean diet rich in fruits, vegetables, and whole grains, avoiding added sugars and saturated fats) to promote weight loss and improve overall health.
Engaging in physical activity for at least 150 minutes per week of aerobic or strength exercise is recommended to improve insulin sensitivity. In addition, alcohol abstinence is advised to prevent further liver damage.
Pharmacological therapy also contributes to patient improvement:
- Metformin or GLP-1 inhibitors: help control blood glucose levels and reduce weight in individuals with insulin resistance or dyslipidemia.
- GLP-1 receptor agonists: promote weight loss and reverse the metabolic dysfunction underlying the disease.
- Resmetirom: reduces signs of liver fibrosis in advanced cases, thereby lowering the risk of progression to cirrhosis.
