Non-alcoholic fatty liver disease: pathophysiological concepts and treatment options.

Abstract

The prevalence of non-alcoholic fatty liver disease (NAFLD) is continually increasing due to the global obesity epidemic. NAFLD comprises a systemic metabolic disease accompanied frequently by insulin resistance and hepatic and systemic inflammation. Whereas simple hepatic steatosis is the most common disease manifestation, a more progressive disease course characterized by liver fibrosis and inflammation (i.e. non-alcoholic steatohepatitis, NASH) is present in 10-20% of affected individuals. NAFLD furthermore progresses in a substantial number of patients towards liver cirrhosis and hepatocellular carcinoma. Whereas this disease now affects almost 25% of the world´s population and is mainly observed in obesity and type 2 diabetes, NAFLD also affects lean individuals. Pathophysiology involves lipotoxicity, hepatic immune disturbances accompanied by hepatic insulin resistance, a gut dysbiosis and commonly hepatic and systemic insulin resistance defining this disorder a prototypic systemic metabolic disorder. Not surprisingly many affected patients have other disease manifestations and indeed cardiovascular disorders (CVD), chronic kidney disease and extrahepatic malignancies are all contributing substantially to patient outcome. Weight loss and lifestyle change reflect the cornerstone of treatment and several medical treatment options are currently under investigation. The most promising treatment strategies include glucagon-like peptide 1 (GLP-1) receptor antagonists, sodium glucose linked transporter 2 (SGLT2) inhibitors, farnesoid X receptor (FXR) agonists and peroxisome-proliferator-activated receptor (PPAR) agonists. Here we review epidemiology, pathophysiology and therapeutic options for NAFLD.