Pathogenesis of biliary fibrosis

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE

卷:1864

Article

Pinzani, Massimo¹  Tu Vinh Luong² 

[1] UCL Inst Liver & Digest Hlth, London NW3 2QG, England

[2] Royal Free Hosp, Dept Cellular Pathol, London NW3 2QG, England

关键词: Cholestasis;    liver fibrosis;    PBC;    PSC;   

DOI  :  10.1016/j.bbadis.2017.07.026

来源: Elsevier

【 摘 要 】

Chronic cholestatic liver diseases such as primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC) are associated with active hepatic fibrogenesis, and, ultimately, to the development of cirrhosis. However, the precise relationship between cholestasis, in its broad meaning, and liver tissue fibrosis is still poorly defined. Fibrogenesis is currently viewed as a dynamic process that appears strictly related to the extent and duration of parenchymal injury. This relationship is clearly evident in the presence of reiterative hepatocellular necrosis due to viral infection or alcohol abuse. It appears that pure intralobular intrahepatic cholestasis secondary to biliary secretory failure of the hepatocyte, in absence of hepatocellular damage, lobular inflammation and bile duct damage and/or proliferation, is not associated with marked and/or progressive liver tissue fibrosis. In contrast, marked and progressive liver tissue fibrosis always follows liver diseases characterized by chronic inflammatory bile duct damage as seen in PBC and PSC or chronic mechanical obstruction of the biliary tree. Overall, the fibrogenic process in these clinical conditions appears to be related to a more complex interaction between immune/inflammatory mechanisms, cytokine networks and the derangement of the homeostasis between epithelial and mesenchymal cells. The elucidation of these mechanisms is indeed crucial for the identification of potential diagnostic and therapeutic targets.

【 授权许可】

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