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, particularly focusing on fibrosis assessment and addressing cardiovascular risk factors to improve long-term outcomes in affected patients. The analysis found that patients with MASLD have a higher risk of developing type 2 diabetes, chronic kidney disease, and cardiovascular events, with cardiovascular disease emerging as the leading cause of death in these patients, followed by extrahepatic cancers and liver-related complications 1. Disease progression was notable, with non-alcoholic steatohepatitis (NASH) patients showing higher rates of progression to advanced fibrosis and cirrhosis compared to those with simple steatosis, and the presence of fibrosis, particularly advanced fibrosis, was identified as the strongest predictor of adverse outcomes, with mortality risk increasing proportionally with fibrosis stage 1. Key recommendations for the management of MASLD include lifestyle modification, such as weight loss, dietary changes, and physical exercise, as well as optimal management of comorbidities, including the use of incretin-based therapies for type 2 diabetes or obesity, if indicated 1. Additionally, the use of resmetirom, a MASH-targeted treatment, may be considered for adults with non-cirrhotic MASH and significant liver fibrosis, as it has demonstrated histological effectiveness on steatohepatitis and fibrosis with an acceptable safety and tolerability profile 1. Overall, the findings of this study highlight the need for early detection and management of MASLD, with a focus on fibrosis assessment and addressing cardiovascular risk factors to improve long-term outcomes in affected patients.

Some key points to consider in the management of MASLD include:

• The importance of early detection and management of MASLD to improve long-term outcomes in affected patients
• The use of lifestyle modification, such as weight loss, dietary changes, and physical exercise, to improve liver injury and reduce the risk of disease progression
• The optimal management of comorbidities, including the use of incretin-based therapies for type 2 diabetes or obesity, if indicated
• The potential use of resmetirom, a MASH-targeted treatment, for adults with non-cirrhotic MASH and significant liver fibrosis
• The need for ongoing monitoring and follow-up to assess disease progression and adjust treatment as needed.

From the Research

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

• The study found a significant increase in the risk of cardiovascular outcomes, various metabolic outcomes, and all cancers among MASLD patients compared with non-MASLD individuals 2.
• Meta-analysis revealed a hazard ratio (HR) of 1.43 for cardiovascular outcomes, 1.75 for incident hypertension, 2.56 for diabetes, and 1.54 for all cancers among MASLD patients compared with non-MASLD individuals 2.
• The study also found that MASLD patients with advanced liver disease were associated with a significantly greater risk of incident diabetes than those with less severe MASLD 2.
• Liver histology is associated with long-term clinical outcomes in patients with metabolic dysfunction-associated steatohepatitis, with fibrosis stage and lobular inflammation and hepatocyte ballooning grades predicting the risk of long-term outcomes 3.
• The incidence of all-cause mortality increased with disease severity in patients with MASH, with higher fibrosis stage and cirrhosis associated with a higher risk of progression to cirrhosis and liver-related outcomes 4.
• Cardiometabolic comorbidities such as type 2 diabetes and hypertension were prevalent in patients with MASH progression, highlighting the need for early identification and management of MASH to mitigate disease progression and liver-related complications 4.
• Metabolic-dysfunction-associated steatotic liver disease (MASLD) is closely associated with the development and progression of atherosclerosis and cardiovascular disease, with insulin resistance playing a key role in the pathophysiology of MASLD 5.
• Therapeutic interventions for MASLD should aim to reduce body weight and improve coronary risk factors, in addition to improving liver function, with lifestyle modifications, surgical interventions, and medications such as sodium glucose cotransporter 2 inhibitors and glucagon-like peptide-1 receptor agonists showing promise in improving MASLD outcomes 5.
• Metabolic dysfunction-associated steatohepatitis increased the risk of long-term mortality/transplantation and liver-related events in patients with chronic hepatitis B, highlighting the importance of considering the histologic MAFLD phenotype in the management of CHB patients 6.