New drugs for NAFLD: lessons from basic models to the clinic

Abstract

Abstract: The term nonalcoholic fatty liver disease (NAFLD) comprises a spectrum of increasingly harmful conditions ranging from nonalcoholic fatty liver (NAFL) to nonalcoholic steatohepatitis (NASH) to liver fibrosis and end-stage cirrhosis. NAFLD is the currently most common form of chronic liver disease in both adults and children worldwide. As NAFLD evolves as a global pandemic alongside the still growing prevalence of metabolic syndrome, obesity, and diabetes, it is inevitable to develop effective counterstrategies. Over the last decades, great effort has been dedicated to the understanding of the pathogenesis of NAFLD. This includes the development of an array of models for NAFLD, ranging from advanced in vitro (primary cells, 3D cultures, biochip, spheroids, organoids) to in vivo rodent models (particularly in mice). Based on these approaches novel therapies have been proposed and subsequently evaluated for patients with advanced forms of NAFLD, in particular those with NASH and liver fibrosis or cirrhosis. In this review, we delineate the current understanding of disease pathophysiology and depict how novel therapeutic strategies aim to exploit these different mechanisms to ameliorate, treat, or stop progression of NASH. We also discuss obstacles and chances along the way from basic models to promising clinical treatment options. Graphical abstract: [Figure not available: see fulltext.]