Cellular and Molecular Life Sciences

, Volume 73, Issue 10, pp 1969–1987 | Cite as

Pathogenesis of nonalcoholic steatohepatitis

  • Wensheng LiuEmail author
  • Robert D. Baker
  • Tavleen Bhatia
  • Lixin Zhu
  • Susan S. BakerEmail author


Nonalcoholic steatohepatitis (NASH) is a severe form of nonalcoholic fatty liver disease and a risk factor for cirrhosis and hepatocellular carcinoma. The pathological features of NASH include steatosis, hepatocyte injury, inflammation, and various degrees of fibrosis. Steatosis reflects disordered lipid metabolism. Insulin resistance and excessive fatty acid influx to the liver are two important contributing factors. Steatosis is also likely associated with lipotoxicity and cellular stresses such as oxidative stress and endoplasmic reticulum stress, which result in hepatocyte injury. Inflammation and fibrosis are frequently triggered by various signals such as proinflammatory cytokines and chemokines, released by injuried hepatocytes and activated Kupffer cells. Although much progress has been made, the pathogenesis of NASH is not fully elucidated. The purpose of this review is to discuss the current understanding of NASH pathogenesis, mainly focusing on factors contributing to steatosis, hepatocyte injury, inflammation, and fibrosis.


Autophagy Gut microbiota Genetic predisposition Apoptosis Hepatic stellate cells 



Carbohydrate response element binding protein


Cardiovascular disease




Damage-associated molecular patterns


De novo lipogenesis


Endoplasmic reticulum


Electron transport chain


Free fatty acids


Hepatocellular carcinoma




Hepatic progenitor cells


Hepatic stellate cell


Insulin resistance




Nonalcoholic fatty liver disease


Nonalcoholic steatohepatitis


NOD like receptors


Pathogen-associated molecular patterns


Patatin-like phospholipase domain-containing 3


Peroxisome proliferator-activated receptors


Pattern recognition receptors


Polyunsaturated fatty acids


Reactive oxygen species


Short-chain fatty acids


Single nucleotide polymorphism


Sterol regulatory element-binding protein 1c


Transforming growth factor β




Toll like receptors


Vascular endothelial growth factor


Very low density lipoprotein


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Copyright information

© Springer International Publishing 2016

Authors and Affiliations

  1. 1.Department of Pediatrics, Digestive Diseases and Nutrition Center, Women and Children’s Hospital of BuffaloThe State University of New York at Buffalo (SUNY Buffalo)BuffaloUSA

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