MAFLD as part of systemic metabolic dysregulation.

Nonalcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases worldwide. In recent years, a new terminology and definition of metabolic dysfunction-associated fatty liver disease (MAFLD) has been proposed. Compared to the NAFLD definition, MAFLD better emphasizes the pathogenic role of metabolic dysfunction in the development and progression of this highly prevalent condition. Metabolic disorders, including overweight/obesity, type 2 diabetes mellitus (T2DM), atherogenic dyslipidemia and hypertension, are often associated with systemic organ dysfunctions, thereby suggesting that multiple organ damage can occur in MAFLD. Substantial epidemiological evidence indicates that MAFLD is not only associated with an increased risk of liver-related complications, but also increases the risk of developing several extra-hepatic diseases, including new-onset T2DM, adverse cardiovascular and renal outcomes, and some common endocrine diseases. We have summarized the current literature on the adverse effect of MAFLD on the development of multiple extrahepatic (cardiometabolic and endocrine) complications and examined the role of different metabolic pathways and organ systems in the progression of MAFLD, thus providing new insights into the role of MAFLD as a multisystem metabolic disorder. Our narrative review aimed to provide insights into potential mechanisms underlying the known associations between MAFLD and extrahepatic diseases, as part of MAFLD as a multisystem disease, in order to help focus areas for future drug development targeting not only liver disease but also the risk of extrahepatic complications.

Is primary open-angle glaucoma an ocular manifestation of systemic disease?

Primary open-angle glaucoma is currently characterized by a pattern of progressive retinal ganglion cell loss that stems from a complex underlying pathophysiology that remains poorly elucidated. The roles of blood flow and intraocular pressure (IOP) in glaucoma pathogenesis have been extensively studied. Further, it has been established that lowering IOP can slow the progression of glaucoma. In addition, a number of influential factors have emerged and gained momentum over the years. Increasing evidence implicates the contributions of low cerebrospinal fluid pressure, autoimmunity, neurodegeneration, and impaired autoregulation towards glaucoma pathophysiology. We aggregate and explore these different camps of thought that have garnered attention over the last few decades, and, in doing so, aim to challenge the long-standing view of glaucoma as a primary disease of the eye. A shift in our perspective towards understanding glaucoma as an ocular manifestation of systemic dysregulation may lead ultimately to better clinical management of the disease.