Non-alcoholic fatty liver disease--a chronic disease of the 21^st century

Non-alcoholic fatty liver disease (NAFLD) comprises a spectrum of metabolic states ranging from simple steatosis to inflammation with associated fibrosis to cirrhosis. Though accumulation of hepatic fat is not associated with a significant increase in mortality rates, hepatic inflammation is, as this augments the risk of terminal liver disease, i.e., cirrhosis, hepatic decompensation (liver failure) and/or hepatocellular carcinoma. Disease progression is usually slow, over a decade or more and, for the most part, remains asymptomatic. Recent estimates suggest that the global prevalence of NAFLD is high, about one in four. In most cases, NAFLD overlaps with overweight, obesity, cardiovascular disease and the metabolic syndrome with numerous contributing parameters including a dysregulation of adipose tissue, insulin resistance, type 2 diabetes, changes in the gut microbiome, neuronal and hormonal dysregulation and metabolic stress. NAFLD is diagnosed incidentally, despite its high prevalence. Non-invasive imaging techniques have emerged, making it possible to determine degree of steatosis as well asfibrosis. Despite this, the benefit of routine diagnostics remains uncertain. A better understanding of the (molecular) pathogenesis of NAFLD is needed combined with long-term studies where benefits of treatment can be assessed to determine cost-benefit ratios. This review summarizes the current state of knowledge and possible areas of treatment.