A comprehensive lifestyle intervention is the cornerstone and first-line treatment of metabolic dysfunction-associated steatotic liver disease (MASLD). The main goals are sustained weight loss through an energy-restricted, high-quality diet, regular physical activity combining aerobic and resistance exercise, and optimal management of associated cardiometabolic conditions such as obesity, arterial hypertension, dyslipidaemia, and type 2 diabetes mellitus. Alcohol consumption should also be minimized, particularly in patients with advanced liver disease. (PubMed Central (PMC))

Weight reduction

In patients with overweight or obesity, the degree of weight loss is closely related to improvement in liver disease. Current European guidelines recommend aiming for a sustained weight reduction of:

• ≥5% of body weight to reduce hepatic fat content,
• 7–10% to improve liver inflammation and steatohepatitis,
• ≥10% to achieve a meaningful improvement in liver fibrosis.

Even modest sustained weight loss can therefore provide clinically relevant benefits. (PubMed Central (PMC))

Nutrition

Dietary treatment should focus on a long-term reduction in total energy intake rather than on a short-term restrictive diet. A Mediterranean-style dietary pattern is particularly well supported by current evidence. It is characterized by a high intake of vegetables, fruits, legumes, whole-grain products, nuts, seeds, olive oil, fish, and other foods rich in unsaturated fatty acids.

At the same time, the consumption of sugar-sweetened beverages, refined carbohydrates, ultra-processed foods, and foods rich in saturated fats should be limited. Mediterranean-style dietary patterns can reduce hepatic steatosis and improve cardiometabolic risk factors and are associated with a lower risk of cardiovascular disease and type 2 diabetes. Some hepatic benefits may occur even in the absence of substantial weight loss. (PubMed Central (PMC))

Physical activity

Regular physical activity is another essential component of MASLD treatment. Current guidelines recommend preferably more than 150 minutes of moderate-intensity aerobic activity per week, or at least 75 minutes of vigorous-intensity activity, adapted to the individual’s physical capacity and preferences.

A combination of aerobic and resistance exercise is preferable. Resistance training two to three times per week is a reasonable practical target. Importantly, exercise can reduce hepatic steatosis and improve cardiometabolic health even when it does not result in significant weight loss. However, the magnitude of the reduction in liver fat varies considerably between studies; therefore, a fixed reduction of 15–30% should not be expected in every patient. (PubMed Central (PMC))

Pharmacological treatment

Lifestyle modification and treatment of cardiometabolic comorbidities remain essential at all stages of MASLD. Medications such as GLP-1 receptor agonists or other incretin-based therapies should be used when indicated for obesity or type 2 diabetes because substantial weight loss and improved metabolic control may also have beneficial effects on MASLD. (PubMed Central (PMC))

For patients with non-cirrhotic MASH and clinically significant fibrosis, MASH-targeted pharmacotherapy may also be considered.

Resmetirom (Rezdiffra®) is a selective thyroid hormone receptor-β agonist. It received conditional marketing authorization in the European Union in August 2025 and is indicated, in conjunction with diet and exercise, for adults with non-cirrhotic MASH and moderate to advanced fibrosis (F2–F3). (European Medicines Agency (EMA))

In the United States, semaglutide 2.4 mg (Wegovy®) has additionally been approved for adults with non-cirrhotic MASH and F2–F3 fibrosis. This MASH-specific indication does not currently apply to the European Union, where Wegovy is approved primarily for weight management. (U.S. Food and Drug Administration)

Bariatric and metabolic surgery

In patients with obesity and non-cirrhotic MASLD who otherwise meet established criteria for metabolic or bariatric surgery, surgery should be considered because it can produce substantial and sustained weight loss, improve type 2 diabetes and cardiovascular risk factors, and markedly improve liver disease.

The effects may be considerable. In a prospective observational study, MASH had resolved in approximately 84% of patients five years after bariatric surgery. Meta-analyses have also demonstrated improvement or resolution of fibrosis in a substantial proportion of patients, although the degree of fibrosis regression varies according to the patient population and surgical procedure. Roux-en-Y gastric bypass has been associated with improvement or resolution of fibrosis in approximately 30% of patients in pooled analyses. (PubMed Central (PMC))

Bariatric surgery should therefore not be described simply as reducing hepatic steatosis in 50% and fibrosis in 25% of patients; the available evidence shows greater and more variable effects depending on the endpoint studied. In patients with cirrhosis, particularly clinically significant portal hypertension or decompensated cirrhosis, bariatric surgery requires specialist assessment and may be contraindicated. (PubMed Central (PMC))

Long-term adherence

Because MASLD is a chronic disease, the long-term maintenance of lifestyle changes is more important than short-term dietary interventions. Structured programs combining nutritional counselling, regular physical activity, behavioural strategies, self-monitoring, and realistic individualized goals are therefore recommended to improve long-term adherence. (PubMed Central (PMC))