Treatments for NAFLD

Abstract

Non-alcoholic fatty liver disease (NAFLD) is categorised into simple steatosis, termed nonalcoholic fatty liver (NAFL) and nonalcoholic steatohepatitis (NASH). Nonalcoholic steatohepatitis is characterized by steatosis, hepatocyte damage, inflammation and liver fibrosis, which through cirrhosis leads to organ failure, including hepatocellular carcinoma. Development of effective non-alcoholic fatty liver disease therapies depends on basic biomedical research on liver metabolism or the body's response to factors of the metabolic syndrome. In this article, we present important information on in vitro experimental models (including multilayer co-cultures of cells, spheroids, microprocessor technologies, bioprinting) and animal models (diet-induced models, genetic models and models of combinations of various interventions) of non-alcoholic fatty liver disease enabling refinement of therapeutic targets that can accelerate drug development. We also discuss the emerging targets for drug development intended to stop or reverse disease progression. We present research on the reduction of fibrosis in the course of non-alcoholic fatty liver disease and the optimization of brown adipose function (BAT) for mitigating of metabolic syndrome and nonalcoholic steatohepatitis. The development of nonalcoholic steatohepatitis is also associated with the appearance of chronic inflammation. Thus, pro-inflammatory pathways involving inflammatory mediators represent potential therapeutic targets. Weight loss caused by diet and lifestyle changes, as a result reduces the supply of metabolic substrates to the liver, which in turn slows the progression of non-alcoholic fatty liver disease and reduces the process of liver fibrosis. Therefore, the therapy has also focused on metabolic pathways that can be used to treat non-alcoholic fatty liver disease by limiting the supply of metabolic substrates to the liver or to facilitate their degradation. We also discuss different strategies that involve combination therapies.

Keywords

• animal models
• liver disease
• metabolic syndrome
• pharmacological treatments
• steatosis