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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
Review

Abstract

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.

Keywords

Autophagy Gut microbiota Genetic predisposition Apoptosis Hepatic stellate cells 

Abbreviations

ChREBP

Carbohydrate response element binding protein

CVD

Cardiovascular disease

DAG

Diacylglycerol

DAMPs

Damage-associated molecular patterns

DNL

De novo lipogenesis

ER

Endoplasmic reticulum

ETC

Electron transport chain

FFAs

Free fatty acids

HCC

Hepatocellular carcinoma

HH

Hedgehog

HPCs

Hepatic progenitor cells

HSC

Hepatic stellate cell

IR

Insulin resistance

LPS

Lipopolysaccharide

NAFLD

Nonalcoholic fatty liver disease

NASH

Nonalcoholic steatohepatitis

NLRs

NOD like receptors

PAMPs

Pathogen-associated molecular patterns

PNPLA3

Patatin-like phospholipase domain-containing 3

PPARs

Peroxisome proliferator-activated receptors

PRR

Pattern recognition receptors

PUFA

Polyunsaturated fatty acids

ROS

Reactive oxygen species

SCFAs

Short-chain fatty acids

SNP

Single nucleotide polymorphism

SREBP-1c

Sterol regulatory element-binding protein 1c

TGF-β

Transforming growth factor β

TGs

Triglycerides

TLRs

Toll like receptors

VEGF

Vascular endothelial growth factor

VLDL

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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