Korean J Gastroenterol.  2017 Jun;69(6):341-347. 10.4166/kjg.2017.69.6.341.

The Progression of Liver Fibrosis in Non-alcoholic Fatty Liver Disease

• Kim MY

• KMID: 2384360
• DOI: http://doi.org/10.4166/kjg.2017.69.6.341

Abstract

Understanding the pathogenesis of non-alcoholic steatohepatitis (NASH) and its fibrosis progression is still evolving. Nonetheless, current evidence suggests that mechanisms involved are very complex parallel processes with multiple metabolic factors. Lipotoxicity related with excess saturated free fatty acids, obesity, and insulin resistance acts as the central driver of cellular injury via oxidative stress. Hepatocyte apoptosis and/or senescence are also contribute to the activation of inflammasome via various intra- and inter-cellular signaling mechanisms that lead to fibrosis. Current evidence suggests that periportal components, including ductular reaction and expansion of the hepatic progenitor cell compartment, may be involved and that the T-helper 17 cell response may mediate disease progression. This review aims to provide a brief overview of the pathogenesis of NASH and fibrosis progression from inflammation to fibrosis.

Keyword

Non-alcoholic fatty liver disease; Fibrosis; Inflammation; Insulin resistance

MeSH Terms

Aging
Apoptosis
Disease Progression
Fatty Acids, Nonesterified
Fatty Liver
Fibrosis
Hepatocytes
Inflammasomes
Inflammation
Insulin Resistance
Liver Cirrhosis*
Liver*
Non-alcoholic Fatty Liver Disease*
Obesity
Oxidative Stress
Stem Cells
Fatty Acids, Nonesterified
Inflammasomes

Figure

• 

  Fig. 1 Brief summary of the pathogenesis of nonalcoholic steatohepatitis with fibrosis progression. FFA, free fatty acid; TLR, toll-like receptor; DAMPs, damage associated molecular patterns; NFκB, nuclear factor kappa-light-chain-enhancer of activated B cells; JNK, c-Jun N-terminal kinases; MAPK, mitogen-activated protein kinase; TNFα, tumor necrotizing factor-alpha; IL, interleukin; TGFβ, transforming growth factor-beta; MMPs, matrix metalloproteinases; CCL2, chemokine (C-C motif) ligand 2; CXCL16, chemokine (C-X-C motif) ligand 16; CD, cluster of differentiation; NKT, natural killer T; NK, natural killer; Treg, regulatory T cell; Th17, T helper 17 cell; Hh, hedgehog; OPN, osteopontin; DR, ductular reaction; HPC, hepatic progenitor cells; NASH, non-alcoholic steatohepatitis; HSC, hepatic stellate cell.

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