DAY 3 - Metabolic Dysfunction-Associated Steatotic Liver Disease: A New Entity with Its Own Rules

With a new name and the development of new treatment modalities come new opportunities and challenges for clinicians who manage patients with metabolic dysfunction-associated steatotic liver disease (MASLD). Formerly known as non-alcoholic fatty liver disease (NAFLD), MASLD has emerged as a unique entity that reflects a new epidemiologic reality, in which metabolic risk factors have become important drivers of steatotic liver disease. The latest advances in screening modalities and the evolving treatment landscape of MASLD were the focus of multiple presentations at the ACG 2024 Annual Scientific Meeting in Philadelphia, Pennsylvania.

Risk factors for the development of MASLD include metabolic syndrome features as well as certain genotypes associated with this condition. MASLD is diagnosed either on biopsy or through imaging evidence of steatosis infiltrating at least 5% of the hepatocytes, in individuals with at least one metabolic risk factor who consume little or no alcohol, in the absence of any other causes for liver disease. The latest practice guidance includes screening first-degree relatives of patients with advanced fibrosis, as well as patients with type 2 diabetes, who have an elevated risk for MASLD and advanced fibrosis (Ajmera V et al. J Hepatol 2023; 78:471-478).

Given the expanded screening recommendations, the key is to use noninvasive screening modalities for liver stiffness, steatosis, and fibrosis, such as liver elastography (FibroScan) or magnetic resonance elastography (MRE), according to Rohit Loomba, MD, MHSc, Director of the MASLD Research Center at the University of California, San Diego. “In a patient with metabolic risk factors, you want to start with a Fib-4 assessment,” Loomba explained during a session at ACG 2024. “Fib-4 is a clinical prediction tool that includes age, ALT, AST, and platelet count. Once you do that, if the Fib-4 is greater than 1.3, then you do a more specific test to look at fibrosis of the liver. It could be FibroScan or MRE to assess liver stiffness measurement, or a blood test called enhanced liver fibrosis panel.” Based on the findings, patients can then be referred to gastroenterology or hepatology specialists.

The treatment algorithm starts with lifestyle recommendations that address the metabolic risk factors, including obesity, being overweight, or living with type 2 diabetes. These include reduction of caloric intake, weight loss, regular exercise, and limiting alcohol consumption. Management of hyperlipidemia with statins and glycemic control are essential components of the treatment plan, Loomba said. Bariatric surgery can also be considered for individuals with morbid obesity and comorbidities. A weight loss of 7% to 10% is typically necessary to see improvement in liver fibrosis or resolution of steatohepatitis, Loomba explained. Because this is rarely seen in clinical practice, weight loss agents or bariatric surgery are often needed to induce weight loss and see improvement in these parameters.

Various agents in phase 3 clinical development have shown promise in the treatment of MASLD. Among these, resmetirom received regulatory approval for patients with MASH-related moderate to advanced fibrosis without cirrhosis, after achieving resolution of steatohepatits and improvement of fibrosis in the MAESTRO-NASH phase 3 clinical trial. Clinical parameters can help identify patients who are candidates for resmetirom without the use of invasive testing, Loomba said. Although this strategy remains controversial, liver stiffness measurements may be used to assess hepatic steatosis.

Other agents, including glucagon-like peptide-1 receptor agonist semaglutide, pan-PPAR agonist lanifibranor, and PGF21 mimics pegozafermin and efruxifermin have also shown improvement in steatosis, oxidative stress, and metabolic pathway regulation in clinical trials. As data about the latest therapies are still maturing, clinicians should tailor strategies based on patient history and risk profile, considering possible side effects and comorbidities. “Fibrosis improvement requires longer-term treatment and typically involves liver-specific targeted therapies,” Loomba concluded.