Heterogeneity of fibrosis patterns in non-alcoholic fatty liver disease supports the presence of multiple fibrogenic pathways

Skoien, Richard, Richardson, Michelle M., Jonsson, Julie R., Powell, Elizabeth E., Brunt, Elizabeth M., Neuschwander-Tetri, Brent A., Bhathal, Prithi S., Dixon, John B., O'Brien, Paul E., Tilg, Herbert, Moschen, Alexander R., Baumann, Ulrich, Brown, Rachel M., Couper, Richard T., Manton, Nicholas D., Ee, Looi C., Weltman, Martin and Clouston, Andrew D. (2013) Heterogeneity of fibrosis patterns in non-alcoholic fatty liver disease supports the presence of multiple fibrogenic pathways. Liver International, 33 4: 624-632. doi:10.1111/liv.12100

Author Skoien, Richard
Richardson, Michelle M.
Jonsson, Julie R.
Powell, Elizabeth E.
Brunt, Elizabeth M.
Neuschwander-Tetri, Brent A.
Bhathal, Prithi S.
Dixon, John B.
O'Brien, Paul E.
Tilg, Herbert
Moschen, Alexander R.
Baumann, Ulrich
Brown, Rachel M.
Couper, Richard T.
Manton, Nicholas D.
Ee, Looi C.
Weltman, Martin
Clouston, Andrew D.
Title Heterogeneity of fibrosis patterns in non-alcoholic fatty liver disease supports the presence of multiple fibrogenic pathways
Journal name Liver International   Check publisher's open access policy
ISSN 1478-3223
Publication date 2013-04
Year available 2013
Sub-type Article (original research)
DOI 10.1111/liv.12100
Volume 33
Issue 4
Start page 624
End page 632
Total pages 9
Place of publication Malden, MA, United States
Publisher Wiley-Blackwell
Collection year 2014
Language eng
Formatted abstract
Background: Adult non-alcoholic fatty liver disease (NAFLD) involves lobular necroinflammatory activity and fibrosis is typically centrilobular, whereas paediatric NAFLD has predominantly portal fibrosis. The reasons for these differences are unclear. We aimed to determine (a) how centrilobular and portal fibrosis in children relate to histological parameters; and (b) whether atypical fibrosis patterns exist in adults that are unexplained by current fibrogenesis models.

Methods: Histological features of paediatric (n = 38) and adult (n = 56) NAFLD were assessed using conventional scoring systems. Keratin-7 immunostaining was used to assess hepatic progenitor cell numbers and the ductular reaction. Centrilobular and portal components of fibrosis were independently scored and fibrosis patterns were classified according to accepted types. Post-treatment (rosiglitazone/gastric banding) biopsies were also examined in adults.

Results: Twenty-six children (68.4%) had portal-predominant fibrosis, although the typical "adult" pattern was seen in 11 (28.9%). Portal fibrosis was associated with a ductular reaction (P = 0.021) and hepatic progenitor cell expansion (P < 0.001), whereas centrilobular fibrosis was associated with lobular inflammation (P = 0.026) and ballooning (P = 0.001). Before intervention, six adults (10.7%) had atypical fibrosis including 3 (5.4%) with a previously unrecognized pattern of very fine, non-zonal sinusoidal fibrosis. Despite improvements in steatosis and inflammation, more patients developed this unusual pattern after intervention with most having had surgery (9 of 10 adults; P < 0.001).

Conclusion: Differing associations with portal and centrilobular fibrosis in children and atypical fibrosis patterns in adults suggest that multiple fibrogenic pathways exist in NAFLD. This has implications for therapy and understanding pathogenesis.
Keyword Bariatric surgery
Fatty liver
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2014 Collection
School of Medicine Publications
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Citation counts: TR Web of Science Citation Count  Cited 16 times in Thomson Reuters Web of Science Article | Citations
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