Heterogeneity of fibrosis patterns in non-alcoholic fatty liver disease supports the presence of multiple fibrogenic pathways
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 p...
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Published in | Liver international Vol. 33; no. 4; pp. 624 - 632 |
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Main Authors | , , , , , , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
Blackwell Publishing Ltd
01.04.2013
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Subjects | |
Online Access | Get full text |
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Summary: | 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. |
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Bibliography: | National Health and Medical Research Council of Australia The Princess Alexandra Hospital Research and Development Foundation ark:/67375/WNG-79FPBPNP-4 Table S1. Demographic and histological data for the paediatric NASH cohort.Table S2. Distribution of individually scored centrilobular and portal components of fibrosis for the pediatric NASH cohort.Table S3. Demographic and histological data for the adult NAFLD cohort before and after intervention.Table S4. Demographic and histological data for adult NAFLD patients with and without diffuse subsinusoidal fibrosis before intervention.Table S5. Demographic and histological data for adult NAFLD patients with and without diffuse subsinusoidal fibrosis after intervention. The Sasakawa Foundation MSD. The Queensland Government's Smart State Health and Medical Research Fund ArticleID:LIV12100 The Royal Brisbane and Women's Hospital Research Foundation istex:E9FC7D446F6F859202A472B1DEA9208BD3E73838 ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 1478-3223 1478-3231 |
DOI: | 10.1111/liv.12100 |