Nonalcoholic fatty liver disease: from clinical recognition to treatment

Nonalcoholic fatty liver disease (NAFLD) is probably the most common spectrum of metabolic liver disease in the world, encompassing simple steatosis to steatohepatitis, advanced fibrosis, cirrhosis and hepatocellular carcinoma. NAFLD affects a significant part of the general population worldwide. The existing correlation between obesity and NAFLD in combination with the increase in the frequency of obesity in the developed world implies that the incidence and severity of NAFLD will increase in the near future. Newer data support the idea that NAFLD constitutes the more important cause of cryptogenic cirrhosis of the liver and a ground for the development of hepatocellular carcinoma. Liver biopsy remains the most specific and sensitive method to differentiate NAFLD, providing important information on the long-term prognosis of the patients. The 'two hit' hypothesis constitutes the currently prevailing theory for the development of NAFLD and nonalcoholic steatohepatitis. The first 'hit' is purported to be the increase of free fatty acids in hepatocytes, which results in a decrease of beta-oxidation. The second step includes all mechanisms contributing to the development of necroinflammation and fibrosis. Currently, an effective treatment for patients with NAFLD does not exist. Improvement in liver histology remains the primary goal of any therapeutic approach in patients with NAFLD. Viewing NAFLD in the frame of the metabolic syndrome opens the possibility that both the onset of the disease and disease progression could be prevented by changes in lifestyle. Physical exercise and a low calorie diet in combination with the gradual loss of body weight represent the cornerstone for the management of NAFLD patients.