Pathophysiology, development, and mortality of major non-communicable diseases in metabolic dysfunction-associated...

Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as nonalcoholic fatty liver disease and metabolic dysfunction-associated fatty liver disease, has emerged as a critical contributor to the global burden of non-communicable diseases (NCDs). Beyond its hepatic manifestations, MASLD is pathophysiologically connected to broader metabolic dysfunction, including insulin resistance, obesity, type 2 diabetes, and cardiovascular complications. This review critically examines the bidirectional associations between MASLD and major NCDs, including type 2 diabetes, cardiovascular disease, chronic respiratory disease, and cancer, focusing on shared mechanisms such as chronic inflammation, insulin resistance, oxidative stress, lipotoxicity, and epigenetic alterations. Furthermore, we explore disease-specific mortality patterns and mortality-related factors in MASLD patients across NCD domains. This review underscores the need for comprehensive and multidisciplinary strategies that address not only metabolic control but also systemic inflammation, immunometabolic dysregulation, and epigenetic alterations. Such integrative approaches are essential to mitigating the multisystem burden of MASLD and reducing mortality from its associated NCDs.