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

Authors


Correspondence

Assoc. Prof. Andrew D. Clouston, Envoi Specialist Pathologists, 1/49 Butterfield St, Herston, Brisbane, Qld 4006, Australia

Tel: (61-7) 3257 0233

Fax: (61-7) 3257 4833

e-mail: andrewclouston@envoi.com.au

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.

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