What is Non-Alcoholic Fatty Liver Disease (NAFLD), and Why is it Important?

Fatty liver is defined pathologically by stainable fat in hepatocytes (steatosis), or biochemically by hepatic triglyceride content exceeding 5.5%. Non-alcoholic fatty liver disease (NAFLD) is a highly prevalent disorder in which over-nutrition leads to steatosis. The diagnosis is made by the presence of defined risk factors after excluding other causes of steatosis, particularly excessive alcohol intake, hepatitis C virus infection, medications, and single-enzyme defects. The pathology of NAFLD embraces a spectrum from steatosis alone (simple steatosis), through steatohepatitis (NASH), an inflammatory disorder which is associated with hepatocyte injury and frequently fibrosis, leading to cirrhosis and primary liver cancer (hepatocellular carcinoma, or HCC). Thus, one reason why NAFLD is important is that a proportion of those affected may develop cirrhosis complications, such as bleeding esophageal varices, liver failure, and HCC. An outstanding challenge is to identify which NAFLD patients have NASH, and so are at risk of cirrhosis. Another challenge arises from the association of NAFLD (and particularly NASH) with insulin resistance, impaired glucose tolerance or type 2 diabetes, atherogenic dyslipidemia, and metabolic syndrome; these metabolic associations increase the risk of cardiovascular disease and common cancers for people with NAFLD. This chapter introduces the evolving concepts of NAFLD and NASH, the challenging semantics, their high community prevalence, and the complex causative interactions between an altered socioeconomic environment and genetic susceptibility. Key metabolic consequences and liver complications are summarized. Later chapters expand on these issues, on approaches to diagnosis in primary care, NAFLD in specific parts of the world, and the roles of diet and physical activity in etiology and as components of lifestyle interventions designed to reverse fatty liver and obesity, concluding with three state-of-the-art overviews about classes of drugs as possible pharmacotherapy of NASH.