Mapping the literature on improving primary-to-secondary care referrals through the lens of the Quintuple Aim framework for healthcare improvement: a scoping review.

Metabolic dysfunction-associated steatotic liver disease (MASLD) has emerged as the leading cause of chronic liver disease, affecting approximately one-third of adults globally. Although major adverse liver outcomes (MALO) are clinically important, the greatest burden arises from extrahepatic complications, including cardiovascular disease (CVD), chronic kidney disease (CKD), and chronic respiratory disease (CRD). The foundational management of MASLD relies on lifestyle modification; however, effective strategies to prevent its multisystem complications continue to be critically lacking. Current management strategies, largely centered on addressing individual risk factors, such as body mass index (BMI), diet, or physical activity, often yield only modest benefits and neglect the interconnected nature of MASLD pathophysiology. The American Heart Association proposed Life’s Crucial 9 (LC9) as an extension of Life’s Essential 8 (LE8) by incorporating psychological health, a domain often overlooked in conventional cardiometabolic assessment. Although LE8 is associated with a lower risk of adverse liver-related outcomes, evidence specifically among individuals with established MASLD is currently limited. Moreover, whether psychological health provides incremental prognostic information beyond LE8 remains uncertain, particularly as a recent general population study has reported little additional value for cardiovascular and all-cause mortality prediction. Therefore, evaluating whether LC9 adds outcome-specific information beyond LE8 for clinical outcomes in individuals with MASLD represents an important question. Plasma proteomic profiling may help characterize molecular signatures associated with major complications in MASLD. Although individual proteins have been associated with MASLD progression and prior studies have described a proteomic signature of LC9, protein mediators connecting LC9 to MASLD complications have not been systematically identified. We therefore hypothesized that the associations of LC9 with complications and mortality in MASLD may be partly captured by proteomic pathways, allowing mediation analysis to identify potential protein mediators.