Key physiological functions of the liver, including glucose and lipid metabolism, become disturbed in the setting of non-alcoholic fatty liver disease (NAFLD), and may be associated with a systemic inflammatory ‘milieu’ initiated in part by liver-secreted cytokines and molecules.
Consequently, the pathophysiological effects of NAFLD extend beyond the liver with a large body of clinical evidence demonstrating NAFLD to be independently associated with both prevalent and incident cardiovascular disease (CVD), chronic kidney disease, and type 2 diabetes mellitus.
Professor Giovanni Targher and colleagues from Italy examined the association between non-alcoholic fatty liver disease and its relationship with cardiovascular disease and other extrahepatic diseases.
|Other modifiers of risk may include genetic variants|
The magnitude of risk of developing these extrahepatic diseases parallels the underlying severity of NAFLD, such that patients with non-alcoholic steatohepatitis appear to be at greater risk of incident CVD, chronic kidney disease, and type 2 diabetes mellitus than those with simple steatosis.
Other modifiers of risk may include genetic variants, visceral adipose tissue accumulation, dietary intake and the gut microbiome.
Emerging data also suggest that NAFLD may be a risk factor for colonic neoplasia and reduced bone mineral density, especially among men.
Importantly, improvement/resolution of NAFLD is associated with a reduced incidence of type 2 diabetes mellitus and improved kidney function, adding weight to causality and suggesting liver focused treatments may reduce risk of extrahepatic complications.
Professor Targhers' team concludes, "Awareness of these associations is important for the clinicians such that CVD risk factor management, screening for type 2 diabetes mellitus, and chronic kidney disease are part of the routine management of patients with NAFLD."