Risk factors and mechanisms of non-alcoholic steatohepatitis

Abstract

The worldwide proportion of overweight and obese individuals has increased yearly for more than a decade. Along with rates of obesity, the incidence of co-morbid conditions such as type 2 diabetes, cardiovascular disease and liver disease has also increased. The form of liver disease associated with obesity is termed non-alcoholic steatohepatitis (NASH) due to the histological similarities to livers of chronic alcoholics. NASH has been observed in adult as well as pediatric populations; however, the etiology of this disease is still unknown. This review outlines some of the risk factors commonly associated with NASH and describes molecular mechanisms proposed to underlie disease pathogenesis.

Figure 1. Overview of steatohepatitis risk factors and proposed mechanism

Over nutrition can lead to enhanced circulating fatty acids and possibly endotoxemia. Current data suggests that these agents stimulate intracellular signaling via interaction with TLR-4, resulting in the production of cytokines and chemokines, which stimulate inflammation, steatosis and ultimately lead to NASH. Several risk factors such as degree of adiposity, race and the presence of T2DM enhance the severity of NASH.