Editor's Note: With the changing modern lifestyle and dietary patterns, Metabolic Associated Fatty Liver Disease (MAFLD) has gradually become one of the significant public health concerns globally. At the 2024 EASL Congress, there have been groundbreaking developments in the pharmacological treatment of MAFLD. Particularly, studies on the dual receptor agonists for Glucagon-Like Peptide-1 (GLP-1) and Glucose-Dependent Insulinotropic Polypeptide (GIP), survodutide, and tirzepatide, have revealed significant effects in alleviating hepatic steatosis and improving fibrosis. Additionally, due to its association with a range of cardiovascular diseases, diabetes, and other chronic metabolic disorders, the complex relationship between MAFLD and Type 2 Diabetes Mellitus (T2DM) has also garnered significant attention. Our journal had the privilege to interview Professor Arun J Sanyal, the Chair of the NASH Clinical Research Network at the National Institutes of Health, who summarized the latest clinical research progress on MAFLD from this conference and discussed the "Sugar-Liver Co-Management" strategy for patients with MAFLD and T2DM, aiming to provide new insights for clinical treatment and patient management.Hepatology Digest : What are the breakthroughs in the latest clinical research on MAFLD at this year’s EASL Congress?
Professor Sanyal: There have been significant advancements in the treatment of MAFLD in recent years. One of the hot topics of research has been the GLP-1 and GIP agonists. These drugs were originally used primarily for the treatment of diabetes, but recent studies have shown significant therapeutic effects for MAFLD as well.
I believe the most important studies are the ones on the GCG/GLP-1 dual receptor agonist survodutide and the GIP/GLP-1 dual receptor agonist tirzepatide. These studies have shown that both drugs can achieve a resolution rate of 70%-80% for Metabolic Associated Steatohepatitis (MASH) and a resolution rate of 50%-60% for fibrosis. Additionally, the 96-week long-term study data on efruxifermin also showed a fibrosis resolution rate of 75%. With our deepening understanding of the pathogenesis of MAFLD, we can expect even greater breakthroughs in the development of new drugs targeting multiple mechanisms.
Hepatology Digest: What is the association between MAFLD and T2DM, and how does this association increase the risk of adverse liver-related outcomes?
Professor Sanyal: There is a close association between MAFLD and T2DM. Firstly, the liver is one of the important organs regulating blood glucose. When the liver develops steatosis, its ability to regulate blood glucose is impaired, increasing the risk of T2DM. Secondly, MAFLD patients often have metabolic abnormalities such as insulin resistance and abnormal fatty acid metabolism, which are also important mechanisms for the development of T2DM.
Therefore, when MAFLD coexists with T2DM, the patient’s condition becomes more complex and severe. On one hand, MAFLD further exacerbates insulin resistance and metabolic disorders in T2DM patients; on the other hand, T2DM exacerbates liver damage and fibrosis in MAFLD patients. Therefore, for patients with both MAFLD and T2DM, treatment needs to comprehensively consider the conditions and treatment methods of both diseases.
In conclusion, as a chronic metabolic disease, the pathogenesis and treatment methods of MAFLD are complex and diverse. With the continuous deepening of medical research and the emergence of new technologies, we believe that in the future, we will have more means to prevent and treat MAFLD and its related diseases.
Hepatology Digest: With the continuous emergence of clinical trials, what insights can we gain from them to co-manage MAFLD and T2DM?
Professor Sanyal: In clinical practice, a comprehensive treatment strategy can be adopted for patients with MAFLD and T2DM. Firstly, improve the patient’s liver function and metabolic status through drug treatment and lifestyle adjustments; secondly, lower blood sugar for T2DM; finally, for patients with severe liver fibrosis, more active treatment measures are needed to prevent further deterioration of the disease.
These exciting studies reveal a new treatment prospect: GLP-1 receptor agonists, which were originally the benchmark for T2DM treatment, have now bravely entered the field of liver disease. Of course, our team has just successfully completed the liver trial, but this is just the beginning, not the end. We believe that these therapies will eventually become the beacon of hope for MAFLD and T2DM patients to regain their health.
Hepatology Digest: Do you think implementing the “Sugar-Liver Co-Management” strategy would help improve patients’ liver health and other non-liver-related outcomes?
Professor Sanyal: I believe the goal of comprehensive sugar-liver co-management is consistent. Currently, we have enough data to support starting treatment for patients with MAFLD and T2DM from GLP-1 receptor agonists because before cirrhosis, the patient’s main risk comes from cardiovascular aspects, and GLP-1 receptor agonists have benefits for cardiovascular risk. Once severe fibrosis occurs, treatment beneficial to the liver is needed because it is closely related to liver-related outcomes. Although GLP class drugs have promising prospects, they are not conventional available drugs, so GLP-1/GIP and GLP/Glucagon-like peptides are also alternatives. Moreover, other drugs such as resmetirom, play a role in the treatment of metabolic-associated fatty liver disease with fibrosis, and may also show effects in late-stage fibrosis patients. For patients already suffering from cirrhosis, we have not yet established clear treatment methods from the liver’s perspective. Therefore, treatment must be aimed at cirrhosis itself and efforts to reduce muscle depletion to prevent complications of cirrhosis.
