Nonalcoholic steatohepatitis: what we know in the new millennium1

Nonalcoholic steatohepatitis (NASH) is a liver disease characterized by diffuse fatty infiltration and inflammation. The exact prevalence of NASH is unclear, but it is becoming more evident that the disease is much more common than previously thought. Although generally a benign, indolent process, it can progress to advanced liver disease in approximately 15-20% of patients. Clinical characteristics associated with NASH include obesity, hyperlipidemia, diabetes mellitus, and hypertension, all of which have been associated with underlying insulin resistance. Typically, this disease becomes evident in the fourth or fifth decade of life with an equal sex predilection. NASH is thought to be caused, in part, by impaired insulin signaling, leading to elevated circulating insulin levels and subsequent altered lipid homeostasis. This process is likely multifactorial and includes both genetic and environmental factors. Treatment options to date are limited and are based on very small clinical trials. Current investigations are focusing on improving the underlying insulin resistance that has been associated with NASH as well as other therapies that decrease oxidative stress or improve hepatocyte survival.