Since June 2023, a new term has been making the rounds: metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as “non-alcoholic fatty liver disease” (NAFLD). The renaming emphasises the association with metabolic conditions such as obesity, type 2 diabetes (T2D), and cardiometabolic risk factors. Now a new interdisciplinary European guideline has been published that defines MASLD as the combination of steatotic liver disease with one or more cardiometabolic risk factors in the absence of other causes such as alcohol consumption.
But apart from the name, what else has changed?
New name, new approach? Understanding MASLD Clinical Practice Guidelines
The recently published Clinical Practice Guidelines on metabolic dysfunction-associated steatotic liver disease (MASLD) was a joint effort of the European Association for the Study of the Liver (EASL), the European Association for the Study of Diabetes (EASD) and the European Association for the Study of Obesity (EASO). It not only introduces a new name, but also states key recommendations on screening, diagnosis, and treatment. Here we provide an overview with a particular focus on the implications for diabetologists.
Liver disease in a new light
According to the latest 2018 EASL HEPAHEALTH Report, liver disease (all causes) affects from 500 to more than 1,100 people per 100,000 across European countries. Although harmful alcohol use and viral infections were more prominent causes in the past, MASLD has become the most common chronic liver disease, with a global prevalence of 30 % according to the recent guideline. The new MASLD subcategory (figure 1) will hopefully improve the identification of patients with shared metabolic characteristics, help to focus research efforts and reduce the stigma associated with previous terminology. In addition to steatosis, MASLD includes metabolic dysfunction-associated steatohepatitis (MASH, formerly NASH), fibrosis, cirrhosis, and MASH-related hepatocellular carcinoma (HCC).
According to the latest 2018 EASL HEPAHEALTH Report, liver disease (all causes) affects from 500 to more than 1,100 people per 100,000 across European countries. Although harmful alcohol use and viral infections were more prominent causes in the past, MASLD has become the most common chronic liver disease, with a global prevalence of 30 % according to the recent guideline. The new MASLD subcategory (figure 1) will hopefully improve the identification of patients with shared metabolic characteristics, help to focus research efforts and reduce the stigma associated with previous terminology. In addition to steatosis, MASLD includes metabolic dysfunction-associated steatohepatitis (MASH, formerly NASH), fibrosis, cirrhosis, and MASH-related hepatocellular carcinoma (HCC).
Figure 1: Flowchart defining subcategories of steatotic liver disease (SLD) by aetiology. MASLD is defined as the presence of hepatic steatosis and of one or more cardiometabolic risk factors in the absence of other identifiable causes such as alcohol con
Diabetes as a major risk factor
MASLD mainly affects men over 50, postmenopausal women, and those with multiple cardiometabolic risk factors, including obesity, insulin resistance, hypertension and dyslipidaemia. “Given that MASLD is a highly prevalent disease, it is important to start applying case-finding strategies to identify individuals with MASLD with liver fibrosis,” says Amalia Gastaldelli, member of the EASD MASLD Guideline Panel. “Non-invasive tests should be applied to all individuals with cardiometabolic risk factors, abnormal liver enzymes, and/or radiological signs of hepatic steatosis, particularly in the presence of T2D or obesity with additional metabolic risk factors,” she adds.
According to the guideline, T2D and obesity have the greatest impact on the development and progression of MASLD, cirrhosis, and HCC. Approximately one third of people with T2D have advanced stages of fibrosis, and T2D is associated with HCC and liver-related deaths. Particularly in the presence of severe insulin resistance, the progression of MASLD or MASH can be rapid. Therefore, people with type 2 diabetes are an important group at risk of developing MASLD.
Non-invasive screening and monitoring
Non-invasive scores can be used to determine the presence or stage of fibrosis, starting with blood tests and adding imaging techniques for further clarification. This is preferred to standard liver enzyme testing and should be reassessed every 1 to 3 years in low-risk individuals. For people already diagnosed with MASLD, the guideline recommends regular assessment of blood biomarker scores and elastography to rule out advanced fibrosis. Liver biopsy is usually not required to monitor disease progression, but remains the necessary tool to diagnose steatohepatitis. In cases of MASLD-related cirrhosis, the guideline recommends that patients should be included in HCC surveillance programmes.
Pharmacological treatments under investigation
There are currently no drugs approved in Europe that specifically target liver damage in MASH. However, the US Food and Drug Administration (FDA) granted accelerated approval for the thyroid hormone receptor beta-selective agonist resmetirom in March 2024, making it the first available treatment option. Resmetirom is currently also under review by the European Medicines Agency (EMA).
Thus the guideline states:
If approved locally and dependent on the label, adults with non-cirrhotic MASH with significant liver fibrosis (stage ≥2) should be considered for treatment with resmetirom as a MASH-targeted therapy, as this treatment demonstrated histological efficacy on steatohepatitis and fibrosis in a large Phase III registrational trial with an acceptable safety and tolerability profile (LoE 2, strong recommendation, consensus).
“Moreover, the use of incretin-based therapies such as semaglutide and tirzepatide, if indicated, is recommended,” says Gastaldelli, referring to the fact that while weight loss and glucose-lowering drugs are not recommended as MASH-targeted therapies due to insufficient evidence, they remain important for the management of comorbidities (figure 2).
Figure 2: Treatment recommendations beyond lifestyle modifications in MASLD/MASH. GLP-1 RA: glucagon-like peptide-1 receptor agonists; SGLT2: sodium-glucose cotransporter-2 (adapted from EASL/EASD/EASO, 2024)
Lifestyle modification as an effective measure
While pharmacological treatment options are on the horizon, nonpharmacological treatments remain the cornerstone of MASLD management. “Lifestyle interventions including weight loss and physical activity are essential, alcohol consumption is discouraged, and some foods, such as sugar and refined carbohydrates, saturated fats, ultra-processed foods, and red and processed meats should be avoided/reduced, as all are associated with MASLD risk,” Gastaldelli summarises the guideline recommendations.
Overall, the guideline emphasises the importance of lifestyle modifications and of optimal management of comorbidities, and it encourages multidisciplinary approaches to ensure the best possible improvement of both hepatic and extrahepatic aspects of the disease.
To read the executive summary visit: https://diabetologia-journal.org/wp-content/uploads/2024/07/EASL-EASD-EASO-Clinical-Practice-Guidelines-on-MASLD-ESM.pdf
To read the full paper visit: https://www.journal-of-hepatology.eu/article/S0168-8278(24)00329-5/fulltext
Author: Hanna Gabriel, BA MSc. Any opinions expressed in this article are the responsibility of EASD e-Learning.
While pharmacological treatment options are on the horizon, nonpharmacological treatments remain the cornerstone of MASLD management. “Lifestyle interventions including weight loss and physical activity are essential, alcohol consumption is discouraged, and some foods, such as sugar and refined carbohydrates, saturated fats, ultra-processed foods, and red and processed meats should be avoided/reduced, as all are associated with MASLD risk,” Gastaldelli summarises the guideline recommendations.
Overall, the guideline emphasises the importance of lifestyle modifications and of optimal management of comorbidities, and it encourages multidisciplinary approaches to ensure the best possible improvement of both hepatic and extrahepatic aspects of the disease.
Key Points:
- MASLD replaces NAFLD and highlights the association with metabolic conditions such as type 2 diabetes and obesity.
- Early detection of MASLD in people with T2D, abdominal obesity or abnormal liver tests using non-invasive methods and regular monitoring is recommended.
- T2D and obesity are major risk factors for the development of MASLD and its progression to fibrosis, cirrhosis, and liver cancer.
- Lifestyle changes such as weight loss and exercise are crucial in the management of MASLD. Resmetirom is the first MASH-targeting drug approved by the FDA and is under review by the EMA.
To read the executive summary visit: https://diabetologia-journal.org/wp-content/uploads/2024/07/EASL-EASD-EASO-Clinical-Practice-Guidelines-on-MASLD-ESM.pdf
To read the full paper visit: https://www.journal-of-hepatology.eu/article/S0168-8278(24)00329-5/fulltext
Author: Hanna Gabriel, BA MSc. Any opinions expressed in this article are the responsibility of EASD e-Learning.