Metabolically Healthy Obesity and Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD): Navigating the Controversies in Disease Development and Progression

Purpose of ReviewThe natural course of metabolic dysfunction-associated steatotic liver disease (MASLD) in the population with metabolically healthy obesity (MHO) has not been adequately explored. In the present narrative review, we summarize the evidence regarding the association between MHO and MASLD prevalence, incidence and progression.Recent FindingsCross-sectional, population-based, cohort studies have shown an increased prevalence of hepatic steatosis and fibrosis in subjects with MHO compared with metabolically healthy non-obese individuals (MHNO). In large-scale longitudinal cohort studies among metabolically healthy subjects, increasing body mass index (BMI) has been found to be independently associated with an increased incidence of MASLD and progressive hepatic fibrosis over a mean follow-up period of 2.2-7.7 years. With regard to advanced MASLD, the prevalence of steatohepatitis and clinically significant liver fibrosis is lower in MHO compared with subjects with metabolically unhealthy obesity (MUO). The presence of MASLD has been proposed as a strong risk factor for metabolic health deterioration in MHO. Furthermore, subjects with MHO and MASLD display an elevated 10-year cardiovascular risk and a three-fold increased risk of incident diabetes compared with MHO without MASLD. MASLD may also predict the failure to convert from MUO to MHO after a weight loss intervention. Subjects with MHO have an increased prevalence of MASLD and hepatic fibrosis risk. We suggest that subjects with MHO and MASLD cannot be characterized as truly metabolically healthy, and we emphasize the need to incorporate hepatic health assessment into the MHO definition, to improve its predictive value for cardiometabolic outcomes.