Fatty liver (commonly known as liver fat) is characterized by the deposition of triglycerides and cholesterol within hepatocytes, a condition called steatosis. Fatty liver is the most common cause of chronic liver disease worldwide, with an estimated one in three people in the general population suffering from liver steatosis.
As of the summer of 2023, the official name for fatty liver is Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD). The advantages of this new name (MASLD) include, among others, highlighting the close relationship between this liver disease and metabolic syndrome (Metabolic dysfunction-associated).
Indeed, most patients suffering from MASLD are usually overweight or obese, while they very often suffer from dyslipidemia, arterial hypertension and diabetes mellitus within the framework of the so-called metabolic syndrome.
Strong relationship between MASLD and Diabetes Mellitus
It is estimated that up to 70% of patients with type 2 diabetes mellitus (T2DM) suffer from MASLD. In fact, it seems that the relationship between T2DM and MASLD is close and bidirectional. More specifically, the presence of MASLD is a strong risk factor for developing T2DM. Obese individuals with MASLD in particular are 9-10 times more likely to develop T2DM over time, compared to the general population.
Strikingly, among individuals with MASLD, the presence of T2DM has been associated with a significantly higher risk of liver cirrhosis and hepatocellular carcinoma. Furthermore, the presence of MASLD in patients with T2DM is associated with an increased risk of cardiovascular morbidity and mortality.
Consequently, the coexistence of T2DM and MASLD is very common, and in these patients, optimal control of T2DM is a cornerstone of MASLD treatment. Significant help in this goal can be provided by adopting the Mediterranean diet, muscular exercise, weight loss, and the selection of appropriate medications, such as GLP-1 agonists, which, in addition to having an antidiabetic effect, can reduce body weight and at the same time have a favorable effect on MASLD.
Dietary management of MASLD
All scientific organizations provide their own dietary and lifestyle recommendations for the management of patients with MASLD. The most basic guidelines are:
- Reducing calorie intake for weight loss of 5-10%, which is considered particularly effective in improving liver damage.
- Adopting the Mediterranean diet, which is a diet high in monounsaturated and polyunsaturated fats, antioxidants and anti-inflammatory compounds, while reducing the consumption of red and processed meat.
- Increasing the consumption of foods rich in fiber, which improve insulin sensitivity and may help reduce visceral fat, which is associated with the accumulation of fat in the liver.
- Incorporating proteins, especially plant-based ones, which provide beneficial nutrients that support liver function.
- Avoiding or minimizing alcohol intake, since even moderate alcohol consumption can worsen liver damage by increasing oxidative stress.
- Drinking coffee, in an amount of 2-3 cups of black coffee (without milk and sugar) per day, as it has been associated with reduced liver inflammation and progression of fibrosis due to the antioxidant compounds it contains.
New drugs in the treatment of MASLD
Recently, the US Food and Drug Administration (FDA) approved the first drug (resmetirom) for adult patients with MASLD who are in the pre-cirrhotic stages of the disease. Resmetirom is administered orally, one pill per day at a dosage depending on the patient’s body weight (one pill of 80 mg per day for body weight <100 Kg, one pill of 100mg per day for body weight >100 Kg).
The particular mechanism of action of the drug is of interest, as it exerts its beneficial effects through stimulation of the β receptors of thyroid hormones located in the liver. In this way, the drug seems to cause the removal of the “local” hepatic hypothyroidism that characterizes patients with MASLD, thus reducing not only the fat in the liver but also stopping the progression to cirrhosis.
Resmetirome appears to act selectively on the liver, resulting in an excellent safety profile without particular side effects (mainly nausea and increased bowel movements are reported), which is very important for this category of drugs. However, the high cost of the drug is a point of intense concern, as it is a treatment for a very common disease, while the decision on approval or not by the European Medicines Agency (EMA) is expected in 2025.
The future in the treatment of MASLD looks very promising, as new very effective drugs are already in advanced stages of clinical trials, and some of them are expected to be approved and available in the coming years. However, this does not negate the need for awareness and interdisciplinary cooperation between different specialties (hepatologists, diabetologists, cardiologists, dietitians) for the optimal treatment of patients with MASLD.
