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).