Should combination therapy be the paradigm for future nonalcoholic steatohepatitis clinical trials?

摘要

Nonakoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in the United States and consists of a spectrum of diseases ranging from relatively benign steato-sis to more aggressive steatohepatitis (NASH), which can lead to cirrhosis and liver failure. Obesity, type 2 diabetes, and metabolic syndrome are closely associated with NAFLD and NASH. Adipose tissue insulin resistance is believed to be one of the fundamental mechanisms leading to an increased hepatic influx of nonesterified fatty acids (NEFA). In addition, increased de novo lipogenesis and dietary intake also contribute to the accumulation of hepatic lipids. An increased hepatic fatty acid load is thought to be lipo-toxic, either through toxic lipid-intermediaries or by causing oxidative stress.