Nonalcoholic fatty liver disease (NAFLD) was first described as a distinct clinical entity four decades ago. However, the condition has become the centre of attention within hepatology owing to its high prevalence and growing contribution to the burden of end-stage liver disease in the general population. This Perspective provides an overview on the development of knowledge related to NAFLD with a focus on landmark findings that have influenced current paradigms and key knowledge gaps that need to be filled to make progress. Specifically, a timeline of scientific discovery of both basic disease mechanisms (with a focus on human data) and the evolution of knowledge about the clinical course of the disease is provided and related to current approaches to treat and eventually prevent NAFLD.
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The author acknowledges funding from NIH project RO1 DK 105961.
A.J.S. is President of Sanyal Biotechnology and has stock options in Akarna, Durect, Exhalenz, Genfit, Haemoshear, Indalo and Tiziana. He has served as a consultant to AbbVie, Amarin, Ardelyx, Astra Zeneca, Boehringer, Conatus, Fibrogen, Genfit, Gilead, Jannsen, Lilly, Nimbus, Nitto Denko, Novartis, Pfizer, Salix, Takeda, Tobira and Zafgen. He has been an unpaid consultant to Affimune, Bristol Myers Squibb, Chemomab, Echosens, Fractyl, Galectin, Immuron, Intercept, Nordic Bioscience, Novartis, Novo Nordisk and Syntlogic. His institution has received grant support from Astra Zeneca, Bristol Myers Squibb, Cumberland, Gilead, Intercept, Malinckrodt, Merck, Salix, Shire and Tobira. He receives royalties from Elsevier and UptoDate. Virginia Commonwealth University also has ownership interests in Sanyal Biotechnology.