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Annu Rev Pathol. 2016 May 23;11:451-96. doi: 10.1146/annurev-pathol-012615-044224. Epub 2016 Mar 3.

Nonalcoholic Fatty Liver Disease: Pathogenesis and Disease Spectrum.

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Institute of Cellular Medicine, Medical School, Newcastle University, Newcastle upon Tyne, NE2 4HH United Kingdom; email:


Nonalcoholic fatty liver disease (NAFLD) is the most common cause of liver dysfunction in the Western world and is increasing owing to its close association with obesity and insulin resistance. NAFLD represents a spectrum of liver disease that, in a minority of patients, can lead to progressive nonalcoholic steatohepatitis (NASH), fibrosis, and ultimately hepatocellular carcinoma and liver failure. NAFLD is a complex trait resulting from the interaction between environmental exposure and a susceptible polygenic background and comprising multiple independent modifiers of risk, such as the microbiome. The molecular mechanisms that combine to define the transition to NASH and progressive disease are complex, and consequently, no pharmacological therapy currently exists to treat NASH. A better understanding of the pathogenesis of NAFLD is critical if new treatments are to be discovered.


NAFLD; NASH; genetics; natural history; pathophysiology; steatohepatitis

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