Fernando Bril
The clinical management of metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH) is undergoing rapid evolution, driven by advances in noninvasive diagnostics and the recent approval of liver-directed therapies. Multiple professional societies have issued guidelines and clinical care pathways to address screening, risk stratification, treatment initiation, and monitoring; however, substantial heterogeneity exists across these documents. In this review, we systematically compare major contemporary guidelines from hepatology, gastroenterology, endocrinology, and diabetes societies, highlighting areas of consensus as well as key differences in target populations for screening, noninvasive test thresholds, treatment eligibility criteria, and monitoring strategies. We analyse the methodological underpinnings of these recommendations, emphasising important limitations related to reliance on trial-derived populations, the absence of head-to-head comparisons, and the use of noninvasive test cutoffs extrapolated from highly selected randomised controlled trials. We also discuss how subjective interpretation of emerging evidence, variable consideration of cardiometabolic comorbidities, and limited integration of cost and access considerations contribute to divergent recommendations. Finally, we propose a framework for improving future guidelines, including greater transparency regarding evidence limitations, adoption of prevalence- and outcome-informed thresholds, clearer guidance on therapy sequencing and combination strategies, and a more holistic approach that aligns liver-specific outcomes with broader cardiometabolic risk reduction. As the therapeutic landscape continues to expand, more adaptive and objective guideline frameworks will be essential to optimise real-world implementation and equity of care.