396 Scopus citations


Nonalcoholic fatty liver disease (NAFLD) is the leading chronic liver disease worldwide. Its more advanced subtype, nonalcoholic steatohepatitis (NASH), connotes progressive liver injury that can lead to cirrhosis and hepatocellular carcinoma. Here we provide an in-depth discussion of the underlying pathogenetic mechanisms that lead to progressive liver injury, including the metabolic origins of NAFLD, the effect of NAFLD on hepatic glucose and lipid metabolism, bile acid toxicity, macrophage dysfunction, and hepatic stellate cell activation, and consider the role of genetic, epigenetic, and environmental factors that promote fibrosis progression and risk of hepatocellular carcinoma in NASH.

Original languageEnglish
Pages (from-to)2537-2564
Number of pages28
Issue number10
StatePublished - 13 May 2021


  • fibrosis
  • insulin resistance
  • lipotoxicity
  • liver cancer
  • metabolism-associated fatty liver disease
  • nonalcoholic steatohepatitis


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