Liver fibrosis during the development of biliary atresia: Proof of principle in the murine model

Background The murine model of biliary atresia (BA) is used for examining the pathogenesis of BA. The aim of the study was description of the morphological features and illustrating the detailed development of fibrosis using the Biliary Atresia Research Consortium (BARC) system. Methods Neonatal mice were injected intraperitoneally with rhesus rotavirus (RRV) strain (N = 17). Healthy mice were the control group (N = 29). All mice were sacrificed at 7 or 14 days after birth. Two pathologists examined the morphological features using the BARC system; CK19, αSMA and collagen type I were assessed by immunohistochemistry. Results In RRV mice, portal fibrous expansion with focal bile duct proliferation and strong portal cellular infiltrate was found in contrast to healthy mice. In RRV mice, CK19 bile duct staining was significantly less or absent (p < 0.01), with stronger portal staining of collagen type I (p = 0.02). Expansion of staining for αSMA was more in RRV mice (p < 0.01), but αSMA portal staining was stronger in healthy mice (p = 0.02). Conclusions The morphological features observed in the murine model of BA correspond with the BA characteristics according to the BARC criteria. Fibrosis is an important feature of the model. Therefore, this murine model is useful for investigating the pathogenesis of BA.

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