MASLD and MASH at the crossroads of hepatology trials and cardiorenal metabolic trials

Area of Science:

• Cardiovascular Medicine
• Hepatology
• Nephrology
• Metabolic Disorders

Background:

• Steatotic liver disease (SLD) is a global health issue linked to increased cardiovascular (CV), type 2 diabetes mellitus, and chronic kidney disease risks.
• Shared pathophysiological processes and high prevalence connect cardiometabolic conditions with SLD, highlighting a need for integrated research.
• The MOSAIC meeting convened experts to foster collaboration across metabolic, hepatology, nephrology, and CV fields.

Purpose of the Study:

• To explore novel drug development approaches for simultaneous regulatory approval of treatments across multiple organ systems.
• To investigate the integration of liver and cardiorenal endpoints within single clinical trials.
• To identify the role of non-invasive tests, including biomarkers and imaging, in hepatic and cardiorenal trials.

Main Methods:

• Discussion and overview of cardiovascular, liver, and kidney measurements.
• Consideration of non-invasive tests for trial endpoints, population enrichment, diagnosis, risk stratification, and efficacy assessment.
• Exploration of strategies to define optimal combinations of biomarkers, imaging, and clinical outcomes for future trials.

Main Results:

• Identification of the need for non-invasive tests in clinical trials for SLD and related cardiometabolic conditions.
• Discussion on challenges in accepting these non-invasive tests for regulatory approval.
• Overview of various CV, liver, and kidney measurements discussed at the MOSAIC meeting.

Conclusions:

• Integrated approaches combining liver and cardiorenal endpoints in clinical trials are crucial for efficient drug development.
• Non-invasive tests are vital for assessing treatment efficacy and safety but require validation for regulatory acceptance.
• Collaboration across specialties is essential to address the complex interplay of SLD and cardiometabolic diseases.