Adipose tissue, obesity and non-alcoholic fatty liver disease

The association of obesity with non-alcoholic fatty liver disease (NAFLD) has been established. Obesity has been linked not only to initial stages of the disease, i.e., simple steatosis (SS), but also to its severity. From an epidemiologic point of view, both diseases has an increasing prevalence worldwide. From a pathogenetic point of view, obesity and its associate IR contribute to the initial fat accumulation in the hepatocyte (SS), but also to the progression of SS to nonalcoholic steatohepatitis (NASH), NASH-related cirrhosis and hepatocellular carcinoma (HCC). From a clinical point of view, obesity has increased morbidity and mortality when combined with NAFLD, owing to cardiovascular and liver-specific mortality, including higher HCC risk. From a therapeutic point of view, weight loss is regarded as the cornerstone for the disease prevention and treatment. Although diet and exercise are the first choice to this aim, they are both difficult to achieve and sustain. Thus, the need for pharmacological treatment is considered of high importance. To treat obesity through pharmacologic weight loss, orlistat has been investigated, though with limited efficacy. Currently, liraglutide appears to be more efficacious, but it has not been officially approved for specifically NASH patients. Bariatric surgery is another alternative for severely obese patients showing histological improvement in NASH patients. However, since relative data from randomized trials are very limited, morbid obesity-related NASH patients may be subjected to bariatric surgery only after a careful individualized risk-benefit assessment.