Non-alcoholic Fatty Liver Disease – Current Understanding and Emerging Pharmacological Treatment Targets

Nonalcoholic fatty liver disease (NAFLD) is an “umbrella term” used to de-scribe a spectrum of liver abnormalities that may range from simple steatosis to steatohepatitis all the way to hepatic fibrosis, cirrhosis, and may potentially result in the development of hepatocellular carcinoma (HCC). NAFLD is closely related to metabolic disturbances such as dyslipidemia, obesity, insulin resistance, and diabetes mellitus. An alarming increase in the global prevalence of this disease has been reported. In fact, in Western countries, non-alcoholic steatohepatitis (NASH) is the fastest growing indication requiring liver trans-plantation. Given the increasing rates of obesity and metabolic syndrome, the burden of NAFLD is expected to mirror this trend, making it a major concern for global health. It is therefore of paramount importance to establish a deep understanding of the pathophysiology of this disease as currently no single satisfactory pharmacological therapy is available. This review presents the current understanding of this pathology, with a particular focus on the pathophysiology, and explores the potential existing and emerging therapeutic targets. Specifically, the role of anti-diabetics, statins, and antioxidants such as vitamin E in the therapy of NASH is reviewed. Furthermore, the therapeutic potential of drugs targeting hepatic de novo lipogenesis, farnesoid X receptor agonists, THR-β agonists, immune response related drugs such as those targeting the apoptosis signal-regulating kinase 1 (ASK1), transforming growth factor beta-activated kinase 1 (TAK1), and tumor necrosis factor α and β (TNF-α, TNF-β) among others, is also explored. The role of gut microbiota, lifestyle interventions and bariatric surgery is discussed as well.