Metabolic Dysfunction-Associated Steatotic Liver Disease MASLD (formerly NAFLD/NASH)

A steatotic liver refers to a condition where the body stores too much fat in liver cells. The term "steatotic" comes from Greek (stear = fat) and medically describes the accumulation of fat in liver cells. When more than 5% of liver cells are affected, this is called steatotic liver disease.

Numerous factors can contribute to the development of such steatotic liver disease, including conditions like diabetes and obesity, certain medications, hormonal factors such as thyroid dysfunction, or specific dietary components like saturated fatty acids or alcohol. In some affected individuals, multiple factors play a role. Precise determination of the underlying causes is therefore the first step and an important component in the evaluation of steatotic liver disease. A physical examination is just as important as a detailed assessment of lifestyle, dietary, and drinking habits.

New Terminology and Classification of Metabolic Dysfunction-Associated Steatotic Liver Disease

When metabolic conditions such as obesity, diabetes, or high blood pressure occur together with a steatotic liver, this is called metabolic dysfunction-associated steatotic liver disease (MASLD). This new terminology replaced the previous nomenclature in 2024 and is now used internationally by all leading medical societies.

In the past, the condition was mostly referred to as non-alcoholic fatty liver disease (NAFLD). This diagnosis was made when a steatotic liver was present after excluding increased alcohol consumption. When additional liver inflammation was present, it was called non-alcoholic steatohepatitis (NASH). These terms are now replaced by MASLD and MASH (metabolic dysfunction-associated steatohepatitis).

The new classification recognizes that there are close connections between steatotic liver disease and other metabolic disorders. It is now understood that metabolic dysfunction-associated steatotic liver disease represents liver involvement in metabolic syndrome (the presence of multiple metabolic disorders). An important difference from the previous definition is that moderate alcohol consumption no longer automatically leads to exclusion of the diagnosis. Instead, there is a new category called MetALD (MASLD with moderate alcohol intake) for individuals who have both metabolic risk factors and some alcohol consumption.

Prevalence of this Liver Disease

Steatotic liver disease is very widespread around the world and has become the most common chronic liver disease. Current studies show that more than 30% of the global population is affected. In Switzerland, approximately one quarter of the general population is affected by steatotic liver disease. In Germany and other European countries, these numbers are similar. Concerning is a significant increase in the disease over recent decades, paralleling the increase in obesity, diabetes, and other metabolic disorders.

People from middle age onwards – particularly women after menopause – commonly suffer from steatotic liver disease. However, studies suggest that many adolescents are already affected by the condition. In a recent study from the USA, steatotic liver disease was present in more than one in five adolescents in the general population. The causes are generally considered to be an inactive lifestyle with lack of exercise, unhealthy diet, and obesity. The latter represents the greatest risk factor for metabolic dysfunction-associated steatotic liver disease, but normal-weight individuals can also be affected. Additionally, almost three-quarters of people with diabetes mellitus suffer from additional steatotic liver disease. In some cases, additional factors such as viral liver disease, hormonal disorders, or medications also play a role.

Course of Metabolic Dysfunction-Associated Steatotic Liver Disease

Often, metabolic dysfunction-associated steatotic liver disease is present for many years before it is noticed. While the disease itself causes few symptoms in this early stage, the risk of severe cardiovascular diseases such as heart attacks (cardiovascular risk) is already increased. In fact, cardiovascular events are the most common cause of death in people with MASLD, even before liver-related complications.

Additionally, steatotic liver disease leads to inflammatory changes in the liver, with pronounced inflammation in the steatotic liver called steatohepatitis (MASH). This inflammation damages liver cells and forms scars in the liver. This scarring is called liver fibrosis, which can progress to liver cirrhosis (complete scarring). When liver cirrhosis is present, the risk of liver cell cancer (hepatocellular carcinoma; HCC) increases. In metabolic dysfunction-associated steatotic liver disease, liver cell cancer can also occur before cirrhosis develops. Liver cirrhosis is a serious condition that has many life-threatening complications in addition to liver cancer. Close medical care with involvement of a liver specialist is therefore necessary early on to prevent severe courses.

Symptoms

Metabolic dysfunction-associated steatotic liver disease often initially runs silently and usually causes few, sometimes no symptoms at all. Pressure sensation in the right upper abdomen, feeling of fullness, fatigue, and concentration problems can occur. These symptoms occur more frequently when additional inflammation of the steatotic liver (MASH) is present.

Even advanced liver scarring (liver fibrosis) and liver cirrhosis can remain unnoticed for long periods, as symptoms are often non-specific. The disease often manifests with increased fatigue or itching. Yellow discoloration of skin or eyes (jaundice), rapid increase in abdominal circumference with ascites, frequent infections, severe fatigue and confusion, as well as increased bleeding tendency indicate a severe course and should be evaluated by a doctor immediately.

Diagnosis and Early Detection

The diagnosis of MASLD today follows a structured approach. Often, liver steatosis (fat accumulation) is discovered as an incidental finding during an abdominal ultrasound examination. Elevated liver values in the blood can indicate steatotic liver disease with inflammation, but often the values are completely normal or only slightly elevated.

Current guidelines recommend targeted screening in risk patients, particularly in people with type 2 diabetes, obesity (BMI ≥30 kg/m²), or metabolic syndrome. For the diagnosis of MASLD, in addition to hepatic steatosis, at least one of the following cardiometabolic risk factors must be present: overweight or obesity, type 2 diabetes, arterial hypertension, dyslipidemia, or metabolic syndrome.

To make an accurate diagnosis and determine the extent of liver changes, further examinations are often needed. Special non-invasive tests such as the FIB-4 score or special ultrasound examination of the liver (e.g., Fibroscan) are helpful, which can more accurately determine steatosis and liver hardening due to scarring or inflammation. In unclear findings, a tissue sample from the liver (liver biopsy) may be necessary. In the removed tissue, liver cells with fat deposits, inflammation, and scarring can be visualized under the microscope. This often allows precise classification of the disease stage as well as exclusion of other liver diseases.

Treatment Options

The treatment of MASLD has developed significantly in recent years. While no specific drug therapies were available for a long time, there are now first approved medications and promising therapeutic approaches.

Drug Therapy

Since 2024, Resmetirom is the first medication specifically approved for MASH available in the USA. It is approved for patients with non-cirrhotic MASH and significant liver fibrosis (stage F2 or higher). For patients in the cirrhotic stage, there is currently no specific drug therapy for MASH, but various medications are being studied in clinical trials.

Additionally, certain medications originally developed for diabetes and obesity have proven helpful in MASLD. These include GLP-1 receptor agonists such as Semaglutide and Tirzepatide, which not only lower blood sugar and help with weight loss but can also have positive effects on the liver. SGLT2 inhibitors can also be beneficial in patients with type 2 diabetes.

Lifestyle Interventions

Lifestyle interventions remain the foundation of any MASLD treatment and are often very successful and have few side effects. Through weight reduction of 7-10% of body weight in overweight individuals and 3-5% in normal-weight affected individuals, the disease can be significantly improved or – especially in early stages – even completely cured.

This weight reduction should be achieved through healthy, balanced dietary changes with moderate reduction of daily calorie intake as well as increased physical activity. A Mediterranean diet with lots of vegetables, whole grains, healthy fats, and moderate consumption of lean meat and fish is recommended. Even small changes, such as avoiding sugary drinks and juices or taking stairs instead of elevators, can make a big difference.

For larger changes, however, any existing conditions, particularly heart disease, high blood pressure, and diabetes, should be considered. It is therefore advisable to discuss major lifestyle changes with your family doctor, diabetologist, cardiologist, or liver specialist beforehand.

Alcohol Consumption

Regarding alcohol consumption, understanding has changed with the new MASLD definition. While previously any alcohol consumption led to exclusion diagnosis, today it is viewed more differentially. With moderate alcohol consumption (up to 20-50g daily in women, 30-60g in men), this is called MetALD. Nevertheless, reduction or, in advanced stages, complete abstinence from alcohol is recommended, as alcohol can worsen liver damage.

Bariatric Surgery

In patients with MASLD and severe obesity, bariatric surgery (obesity surgery) can be an option. This can not only lead to significant weight loss but also significantly improve liver changes.

Risks from Metabolic Dysfunction-Associated Steatotic Liver Disease

Despite the often symptom-free and complaint-free course, metabolic dysfunction-associated steatotic liver disease is dangerous. The greatest risk paradoxically lies not in liver-related complications but in cardiovascular events. Most deaths among patients with steatotic liver diseases are due to cardiovascular events such as heart attacks or strokes. This underscores the importance of holistic care that keeps not only the liver but also cardiovascular risk in view.

Additionally, however, some affected individuals develop serious liver disease with liver cirrhosis or liver cell cancer. The proportion of patients who develop severe disease is overall small but increases significantly with disease duration and when additional inflammation of the steatotic liver (MASH) is present. Due to the overall very high number of affected individuals worldwide, metabolic dysfunction-associated steatotic liver disease will become the main indication for liver transplantation in the coming years.

Outlook and Research

Research on MASLD is developing rapidly. In addition to Resmetirom, numerous other medications are in clinical development. Non-invasive diagnostic procedures are also being continuously improved to make liver biopsies even less necessary in the future.

An important focus is on early detection and prevention. Through better screening programs and education, affected individuals should be identified and treated earlier before serious complications occur.

For patients in Switzerland, there is the possibility of participating in clinical studies. This should be evaluated and conducted together with a liver center. SwissHepa supports affected individuals in obtaining information about current studies and treatment options.