The portal inflammatory infiltrate and ductular niche in non-alcoholic fatty liver disease

Gadd, V., Skoien, R., Fagan, K., Irvine, K., Powell, E. and Clouston, A. (2013). The portal inflammatory infiltrate and ductular niche in non-alcoholic fatty liver disease. In: Australian Gastroenterology Week 2013, Melbourne Australia, (9-10). 7-9 October 2013. doi:10.1111/jgh.12365


Author Gadd, V.
Skoien, R.
Fagan, K.
Irvine, K.
Powell, E.
Clouston, A.
Title of paper The portal inflammatory infiltrate and ductular niche in non-alcoholic fatty liver disease
Conference name Australian Gastroenterology Week 2013
Conference location Melbourne Australia
Conference dates 7-9 October 2013
Journal name Journal of Gastroenterology and Hepatology   Check publisher's open access policy
Place of Publication Richmond Australia
Publisher Wiley-Blackwell Publishing Asia
Publication Year 2013
Sub-type Published abstract
DOI 10.1111/jgh.12365
ISSN 0815-9319
1440-1746
Volume 28
Issue S2
Start page 9
End page 10
Total pages 2
Language eng
Formatted Abstract/Summary
Introduction: Progressive non-alcoholic fatty liver disease (NAFLD) is characterised by portal fibrosis, which is associated with a ductular reaction (DR). Growing evidence implicates portal inflammation as a key predictor of histological progression of NAFLD. We hypothesise that the manifestation of portal fibrosis and a pro-fibrogenic DR is driven by cross-talk between diverse infiltrating immune cells. Although numerous cytokines and multiple individual cell types have been implicated in NAFLD pathogenesis, the composition of the portal and peri-ductal inflammatory infiltrate has not been systematically investigated.

Methods:
Liver biopsy sections from 32 NAFLD patients were immunostained for keratin-7 to highlight the DR, and co-stained for markers of candidate cellular components of the portal inflammatory infiltrate, including CD3, CD8, CD20, CD68, neutrophil elastase (NE), IL-17 and MMP-9. Fresh-frozen liver biopsy samples were available from 23 NAFLD patients for analysis of Collagen-1A and inflammatory gene expression (TGFβ, IL-1β, TNFα, IL-6, IFN-γ, IL-4 and IL-10).

Results: Inflammatory cells within the portal tracts were more numerous than centrilobular regions. The portal inflammatory compartment was comprised of a mix of inflammatory cells, including T cells, B cells, macrophages and neutrophils. Significant portal infiltration was not observed until the presence of progressive NASH (fibrosis stage 2–4) (all P < 0.05) with the exception of macrophage numbers, which increased with the appearance of simple steatosis (P < 0.01) as well as progressive NASH (P < 0.001) when compared with non-diseased control livers. Portal inflammatory cells were present in the peri-ductular inflammatory niche and cell numbers correlated with increasing grade of DR (all P < 0.05) and stage of fibrosis (all P < 0.001). Collagen-1A mRNA was elevated in patients with simple steatosis and highest in progressive NASH (P < 0.001). TNFα, IL-1β and IL-6 were highly expressed with progressive NASH (P < 0.05) whereas TGFβ, IFN-γ, IL-4 and IL-10 showed no association with disease state and progression. Elevated levels of pro-inflammatory cytokines TNFα and IL-1β occurred before significant portal inflammatory infiltration (P < 0.05). Functional markers highlighted IL-17 production by a subset of neutrophils and MMP-9 by a subset of portal and lobular macrophages.

Conclusion: Cell phenotypes and subsequent signalling are greatly influenced by their microenvironments. A modified hepatic inflammatory environment likely influences resident inflammatory cell phenotypes, and may promote a profibrogenic DR and further infiltration of inflamed portal tracts.
Q-Index Code EX
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Conference Paper
Collection: School of Medicine Publications
 
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