Title: Su1089 – Disruption of the Intestinal Barrier Aggravates Immunemediated Hepatitis
Abstract: Aims:The intestinal mucosa plays an important role as a barrier between intestinal microbiota and circulatory system.This study is to analyze the role of intestinal barrier in AIH to provide a direction for explaining the pathogenesis of AIH and exploring new treatment strategies.Methods: 14 cases of AIH patients(6 without cirrhosis,8 with cirrhosis) and 10 cases of healthy controls were enrolled.The Intestinal permeability was measured by serum D-Lac,-DAO levels.The mechanical and immune intestinal barriers were measured through realtime-PCR,western blot and immunohistochemical method.30 female BALB/c mice were randomly divided into five groups including blank group, DSS group, ConA group, DSS+ConA group, and DSS+bacteria+ConA group.Groups with DSS drink 1% DSS solution for 7 days.The DSS+bacteria+ConA group was treated with Bifidobacterium daily via gavage.Groups with ConA received ConA intravenously 12 hours before the end of the 7th day.Serum transaminase levels, liver and intestinal HE staining and the expression of ZO-1, Occludin were measured.Results: Functional and structural changes of intestinal barrier in AIH patients:1.Compared with the healthy controls,the AIH patients without cirrhosis have higher serum D-Lac and DAO levels,and the increased level was more significant in patients with cirrhosis.2.The patients with cirrhosis have significantly lower expression of ZO-1 and Occludin in terminal ileal mucosa.The expression level of ZO-1 in patients without cirrhosis was lower.3.The number of ileal mucosal macrophages increased in AIH patients.Especially in patients with cirrhosis,the number of macrophages significantly increased.4.The expression of IL-2 and IFN-γ in patients with cirrhosis was significantly higher.While the expression of IL-10 in both cirrhosis and non-cirrhosis patients were significantly lower.5.The noncirrhosis patients have higher TLR4 levels in ileum mucosa,and the increased level was more significant in patients with cirrhosis.6.The level of sIgA protein in patients with cirrhosis was significantly decreased.The role of intestinal barrier in the pathogenesis of ConAinduced hepatitis in mice:1.Compared with the blank group, the DSS group had lower ZO-1 and Occludin levels only.While the ConA group had higher transaminase levels only.2.Compared with ConA group, the DSS+ConA group had lower ZO-1 and Occludin levels, higher transaminase levels and higher liver inflammatory activity score.Compared with DSS+ConA group, the DSS+bacteria+ConA group had higher ZO-1 and Occludin levels, lower transaminase levels and the liver inflammatory activity score also decreased.Conclusions: This study innovatively suggested that the intestinal barrier in AIH patients was destroyed,and the damage was more significant in patients with cirrhosis.Disruption of the intestinal barrier could aggravate immune-mediated hepatitis.