Reframing MASLD: A Hepatic Condition With Systemic Clinical Impact

This review synthesizes current evidence describing the systemic implications of metabolic dysfunction-associated steatotic liver disease (MASLD), with emphasis on its extrahepatic complications and underlying pathophysiological mechanisms. A narrative literature review was conducted using PubMed/MEDLINE, Scopus, Web of Science, and Google Scholar. The search included studies published between 1999 and 2025 using terms related to MASLD, systemic inflammation, insulin resistance, lipotoxicity, and extrahepatic diseases. MASLD is strongly associated with multiple extrahepatic conditions, including type 2 diabetes mellitus, polycystic ovary syndrome, chronic kidney disease, cardiovascular disease, obstructive sleep apnea, asthma, psoriasis, and various malignancies. Central mechanisms linking MASLD to systemic disease include chronic low-grade inflammation, insulin resistance, adipose tissue dysfunction, dysregulated hepatokine signaling, and lipotoxicity. The severity of liver fibrosis correlates closely with increased morbidity and mortality from both hepatic and non-hepatic causes. MASLD should be considered a systemic metabolic disease rather than an isolated hepatic disorder. Early recognition, multidisciplinary assessment, and proactive management of both hepatic and extrahepatic manifestations are critical to improving long-term patient outcomes. Future research should prioritize mechanistic clarification and integrated care models.