Journal of Gastroenterology

, Volume 47, Issue 3, pp 215–225 | Cite as

Inflammation and fibrogenesis in steatohepatitis

Review

Abstract

Nonalcoholic fatty liver disease consists of a range of disorders characterized by excess accumulation of triglyceride within the liver. Whereas simple steatosis is clinically benign, nonalcoholic steatohepatitis (NASH) often progresses to cirrhosis. Inflammation and fibrogenesis are closely inter-related and are major targets of NASH research. Experimental data have shown that inflammation in NASH is caused by insulin resistance, systemic lipotoxicity due to overnutrition, lipid metabolites, the production of proinflammatory cytokines and adipokines by visceral adipose tissue, gut-derived bacteria, and oxidative stress. In NASH-associated fibrosis, the principal cell type responsible for extracellular matrix production is recognized as the hepatic stellate cell. Although the fibrotic mechanisms underlying NASH are largely similar to those observed in other chronic liver diseases, the altered patterns of circulating adipokines, the generation of oxidative stress, and the hormonal profile associated with the metabolic syndrome might play unique roles in the fibrogenesis associated with the disease. Information on the basic pathogenesis of NASH with a focus on the generation of inflammation and fibrosis will be discussed.

Keywords

Insulin resistance Lipotoxicity Adipokine Oxidative stress Stellate cell 

Abbreviations

CYP2E1

Cytochrome P450 2E1

FFAs

Free fatty acids

FXR

Farnesoid X receptor

HSCs

Hepatic stellate cells

IL

Interleukin

NAFLD

Nonalcoholic fatty liver disease

NASH

Nonalcoholic steatohepatitis

NF-κB

Nuclear factor kappa B

NOX

NADPH oxidase

PPAR

Peroxisome proliferator-activated receptor

ROS

Reactive oxygen species

TGF-β1

Transforming growth factor-β1

TLRs

Toll-like receptors

TNF

Tumor necrosis factor

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Copyright information

© Springer 2012

Authors and Affiliations

  1. 1.Department of Hepatology, Graduate School of MedicineOsaka City UniversityOsakaJapan

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