Study on the mechanism of fibrosis in autoimmune hepatitis / 解放军医学杂志

ABSTRACT

Objective To explore the mechanism of fibrosis in autoimmune hepatitis(AIH). Methods By using synaptophysin (SYN) as a new marker for hepatic stellate cells (HSCs),HSCs,collagen I,collagen IV,and MT-MMP-1 were detected by immunohistochemistry,and the expressions of MT-MMP-1 and TIMP-1 mRNA were assessed by in situ hybridization in liver tissues obtained by needle biopsy from 36 AIH patients. Results The HSCs were observed in the portal tracts,fibrotic septa and lobules of AIH liver tissues where inflammation was active,especially in the interface of inflammatory and non-inflammatory areas. The number of HSCs increased in proportion to the increase in histoligical active index (HAI,Knodell),while the deposition of Col I and Col IV were increased with increase in hepatic fibrosis stages (Knodell). MT-MMP-1 and its mRNA were mainly expressed in mesenchymal cells which were distributed in the areas of interface of inflammation and borders of fibrotic septa. It was also observed in a few hepatocytes. The expression of MT-MMP-1 was parallel to collagen IV distribution,and increased with advancement of HAI and fibrosis stages,reaching the peak at S4-5 stage. In addition,the expression of TIMP-1 mRNA was similar to that of MT-MMP-1 mRNA. Conclusions The results of immunohistochemistry and in situ hybridization suggested persistant active inflammation,triggering the activation and proliferation of HSC,and the resultant deposition of extracellular matrix such as collagen IV and I might be one of pathogenetic mechnisms of hepatic fibrosis in AIH. The increased expression of MT-MMP-1 in liver tissues of AIH in parallel with the advancement fibrotic stages also suggested that the relative lower level of ECM degeneration due to metalloproteinase suppression might be another reason for fibrogenesis and development of fibrosis in AIH. In addition,it was shown that synaptophysin was another good marker for HSC.