Animal models to elucidate the anti-fibrotic effect of steroid on biliary atresia [Poster presentation]

Abstract

<p><strong>Background</strong></p><p>Biliary Atresia (BA) is a rare disease characterized by obliterative cholangiopathy and often results in liver fibrosis. In this study, we performed animal study to evaluate the impact of steroid on BA with emphasis on its anti-fibrotic effect and explore the pathogenesis.</p><p><strong>Methods</strong></p><p>Inoculation of mice at post-natal day 1 with Rhesus rotavirus (RRV) produced the BA symptoms including cholestatic jaundice. Either steroid or Phosphate-buffered saline (PBS) was used to treat the mice from day 21 to 34. Serum samples from mice were collected on day 34. Liver fibrosis was analyzed by Sirius Red staining. Immune cells expression was tested using Immunofluorescence. Hormonal markers were checked from mice serum. Liver organoids were developed from these RRV-infected mice and were analyzed based on morphology and bulk RNA sequencing.</p><p><strong>Results</strong></p><p>Twenty-four mice developed BA features after RRV injection. They were evenly divided into steroid and PBS treatment group. The weight gain of steroid group increased significantly than PBS group (mean gain % in steroid vs PBS = 79.06% vs 23.97%, P<0.0001). Out of 12 mice in the steroid group, there was only one mouse developed liver fibrosis. On the contrary, all mice developed liver fibrosis in the PBS group. Biochemically, the bilirubin and liver parenchymal enzymes were significantly lower than PBS group (P<0.0001). Liver organoids developed from PBS group were mostly “Multi-vacuole”, or “Un-expanded” as compared to steroid group that were mostly “Single-vacuole, Well-expanded”. A total of 6359 differentially expressed genes were found between the two groups. Qualitative analysis of immune cell expression revealed an apparently higher expression in the PBS group than steroid group.</p><p><strong>Conclusions</strong></p><p>Based on our RRV-induced BA animal model, steroid has the potential to mitigate liver fibrosis in biliary atresia.</p>