What are the principal messages of the study on longitudinal outcomes associated with metabolic dysfunction-associated steatotic liver disease (MASLD), a meta-analysis of 129 studies?

From the Guidelines

The principal messages of the study on longitudinal outcomes associated with metabolic dysfunction-associated steatotic liver disease (MASLD) from a meta-analysis of 129 studies indicate that MASLD significantly increases mortality risk and adverse health outcomes, emphasizing the importance of early detection and management through lifestyle modifications and aggressive management of metabolic risk factors 1.

Key Findings

• The analysis found that patients with MASLD have a higher risk of cardiovascular events, chronic kidney disease, hepatic and extrahepatic malignancies, and liver-related outcomes, including liver failure and hepatocellular carcinoma (HCC) 1.
• Patients with more advanced forms of the disease, particularly those with fibrosis, face substantially higher risks of liver-related complications and mortality 1.
• The study also revealed that MASLD is associated with increased risk of developing type 2 diabetes, chronic kidney disease, and certain cancers, especially hepatocellular carcinoma 1.

Management and Treatment

• Lifestyle modification, including weight loss, dietary changes, physical exercise, and discouraging alcohol consumption, as well as optimal management of comorbidities, is advised for adults with MASLD 1.
• Bariatric surgery is also an option in individuals with MASLD and obesity 1.
• If locally approved and dependent on the label, adults with non-cirrhotic MASH and significant liver fibrosis (stage ≥2) should be considered for a MASH-targeted treatment with resmetirom, which demonstrated histological effectiveness on steatohepatitis and fibrosis with an acceptable safety and tolerability profile 1.

Monitoring and Follow-up

• The progressive nature of MASLD highlights the need for regular monitoring of liver health in affected patients, particularly those with risk factors for disease progression such as older age, presence of diabetes, or elevated liver enzymes 1.
• Non-invasive tests, such as blood-based scores (e.g., FIB-4) and imaging techniques (e.g., transient elastography), can be used to rule out/in advanced fibrosis, which is predictive of liver-related outcomes 1.

From the Research

Principal Messages of the Study on Longitudinal Outcomes Associated with Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)

The study on longitudinal outcomes associated with MASLD, a meta-analysis of 129 studies, reveals several key findings:

• A significant increase in the risk of cardiovascular outcomes, including incident hypertension, diabetes, pre-diabetes, metabolic syndrome, and chronic kidney disease, among MASLD patients compared with non-MASLD individuals 2.
• MASLD patients with advanced liver disease were found to be associated with a significantly greater risk of incident diabetes than those with less severe MASLD 2.
• The multisystemic nature of MASLD requires treatment targets to reduce systemic events and end-organ complications 2.
• The development of cardiovascular diseases determines the prognosis of MASLD patients, and therapeutic interventions should aim to reduce body weight and improve coronary risk factors, in addition to improving liver function 3.
• Lifestyle modifications, such as improved diet and increased exercise, and surgical interventions, such as bariatric surgery and intragastric balloons, have shown to improve MASLD by reducing body weight 3.
• Certain medications, including sodium glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1RAs), have been shown to improve coronary risk factors and suppress the occurrence of cardiovascular diseases, as well as improve liver enzymes, hepatic steatosis, and fibrosis 3, 4.

Key Findings and Implications

The study highlights the importance of:

• Monitoring disease progression in MASLD to decrease morbidity, mortality, need for transplant, and economic burden 5.
• Using various biomarkers to monitor disease progression in different care settings 5.
• Identifying baseline predictors of liver disease progression, such as Hispanic ethnicity, baseline BMI-for-age percentile, baseline mean liver fat fraction, and GGT changes over time, to inform clinical monitoring and optimize care in pediatric MASLD 6.
• Recognizing the heterogeneous nature of MASLD, which comprises a hierarchy of metabolic risk factors contributing to the severity of metabolic dysfunction and associated risk of liver and extrahepatic outcomes 4.