NAFLD and NASH: The Metabolically Diseased Liver

Non-Alcoholic Fatty Liver Disease (NAFLD) is the most common chronic liver disease, with a global prevalence of approximately 24% in the general population. It is caused by fat accumulation in the liver secondary to insulin resistance, visceral obesity, and/or features of metabolic syndrome. A genetic susceptibility contributes to the phenotype, accounting for a more severe course of liver disease and the observed clinical variability. In fact, despite liver steatosis being considered a relatively benign entity, inflammation related to oxidative stress and lipid-derived damage may lead to non-alcoholic steatohepatitis (NASH), which constitutes the progressive disease. Accumulation of hepatic fibrosis can lead to cirrhosis and provide the environment for hepatocellular carcinoma. Obese and diabetic individuals represent a well-acknowledged high risk population. The assessment of liver fibrosis plays a crucial role in clinical setting, as liver-related mortality increases parallel to fibrosis stage. A liver biopsy is currently considered the reference standard for the diagnosis of NASH and the fibrosis stage, but many non-invasive tools are used with the aim of replacing histology for diagnosis and prognosis purposes. Blood based scores and liver stiffness are the most widely used and validated tools to assess liver fibrosis. Management of NAFLD resides on environmental interventions, including diet and physical activity to induce weight loss, and avoiding harmful nutrients, including fructose-sweetened beverages and high glycemic index foods, that are directly implied in liver injury. Multiple trials with investigational drugs are currently explored to treat fibrosing NASH, with promising results and it can be expected that a liver direct therapy aiming at steatohepatitis and fibrosis will become available soon.