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Inflammation and fibrogenesis in steatohepatitis

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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.

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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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Acknowledgments

This work was supported by a grant from the Ministry of Health, Labor and Welfare of Japan to N. Kawada (2008–2010), and by a Grant-in-Aid for Young Scientists (B) from the Japan Society for the Promotion of Science through grant 23790806 to H. Fujii (2011).

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The authors declare that they have no conflict of interest.

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  1. Department of Hepatology, Graduate School of Medicine, Osaka City University, 1-4-3, Asahimachi, Abeno-ku, Osaka, 545-8585, Japan

    Hideki Fujii & Norifumi Kawada

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  1. Hideki Fujii
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Correspondence to Norifumi Kawada.

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Fujii, H., Kawada, N. Inflammation and fibrogenesis in steatohepatitis. J Gastroenterol 47, 215–225 (2012). https://doi.org/10.1007/s00535-012-0527-x

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