Nonalcoholic fatty liver disease - current status and future directions.

Nonalcoholic fatty liver disease (NAFLD) has emerged as the most common chronic liver disease worldwide with a reported prevalence ranging 6-33%, depending on the studied populations. It encompasses a spectrum of liver manifestations ranging from simple steatosis (also known as nonalcoholic fatty liver, NAFL) to nonalcoholic steatohepatitis (NASH), fibrosis and cirrhosis, which may ultimately progress to hepatocellular carcinoma. NAFLD is strongly associated with the components of metabolic syndrome, mainly obesity and type 2 diabetes mellitus. NAFLD patients are at increased risk of liver-related as well as cardiovascular mortality. Current paradigm suggests a benign course for NAFL whereas NASH is considered to be the progressive phenotype. Although previously under-recognized accumulating evidence suggests that NAFL may also progress, suggesting a higher number of patients at risk than previously appreciated. Liver biopsy remains the gold standard for definitive diagnosis, but the majority of patients can be diagnosed accurately by noninvasive methods. Approved therapies for NAFLD are still lacking and lifestyle modifications aiming at weight loss remain the mainstay of NAFLD treatment. Intensive research could identify insulin resistance, lipotoxicity and dysbiosis of the gut microbiota as major pathophysiological mechanisms, leading to the development of promising targeted therapies which are currently investigated in clinical trials. In this review we summarized the current knowledge of NAFLD epidemiology, natural history, diagnosis, pathogenesis and treatment and considered future directions.