Application and interpretation of non-invasive testing in MetALD

Metabolic dysfunction and alcohol-related liver disease (MetALD) is a newly defined entity describing individuals with metabolic dysfunction-associated steatotic liver disease (MASLD) and increased alcohol intake, but below the threshold for a primary diagnosis of alcohol-related liver disease (ALD). This narrative review provides a state-of-the-art overview of the clinical application and interpretation of non-invasive tests (NITs) in MetALD. Due to a current paucity of disease-specific data, we evaluate NITS for steatosis, inflammation, fibrosis, and prognostication for MetALD by drawing upon established MASLD research. We further examine methods for evaluating alcohol intake, ranging from comprehensive clinical histories and screening tools to dedicated biomarkers. While MASLD-derived NITs appear applicable to MetALD, episodic binge drinking can confound results. Therefore, accuracy may be improved by incorporating validated binge assessments and ensuring a minimum alcohol-free interval before testing. Finally, this review addresses the role of NITs in clinical trials for MetALD. For years, the histological response of metabolic dysfunction-associated steatohepatitis (MASH) resolution and fibrosis improvement has been the only reasonably likely surrogate endpoint used for accelerated drug approval. Consequently, thousands of patients have undergone invasive repeated liver biopsies, highlighting the need for validated noninvasive alternatives in future drug development. As the regulatory pathway for MetALD drug development is still evolving, there is a critical opportunity to engage stakeholders and implement NIT-based trial designs to improve patient safety and accelerate therapeutic advancement.