Biliary tract inflammatory disorders: Primary sclerosing cholangitis and primary biliary cirrhosis

Abstract

Primary sclerosing cholangitis (PSC) and primary biliary cirrhosis (PBC) are chronic progressive cholestatic diseases that frequently lead to biliary cirrhosis. The exact pathogenesis of these diseases remains elusive but is likely immunologically based. Complications range from fatigue and pruritus to end-stage liver disease. The risk of developing hepatocellular carcinoma is low for patients with PBC, whereas cholangiocarcinoma is common in PSC and carries an ominous prognosis. Although ursodeoxycholic acid is effective in slowing the progression of PBC, no effective medical therapy exists for PSC. Liver transplantation is the only option for patients with end-stage liver disease and yields excellent long-term survival in both groups.

Differential expression of cyclooxygenase-2 (COX-2) in human bile duct epithelial cells and bile duct neoplasm

“…BDC is relatively uncommon, but one of the worst prognostic cancers in abdominal neoplasm. 36,37 Clinical and patholog-ical evidence has suggested that inflammatory conditions involving the bile ducts predispose these ducts to the development of BDC, [39][40][41][42][43][44][45]72 however, the relationship between chronic inflammation and malignant transformation remains unclear. Recently, in many tumors, COX-2 overexpression has been suggested to play an important role in both carciogenesis and increased malignant potential.…”

“…Although both epithelial cells were accompanied with various levels of inflammation, only PSC has the high risk for cholangiocarcinoma (IHBC). [39][40][41] Bile duct epithelial cells in PSC showed higher levels of COX-2 protein, comparable with those in BDC, and these high-level expressions of COX-2 were observed regardless of inflammatory reaction around them. On the other hand, epithelial cells in PBC showed positive staining of COX-2, but the staining levels were moderate, and the expression levels were comparable with those of bile duct epithelial cells in inflammation.…”

“…Both were accompanied with various degree of inflammatory reaction, and PSC is considered to develop cholangiocarcionoma (IHBC), but not PBC. [39][40][41] Main morbid regions of the bile duct have been classically regarded as large and small ones, for PSC and PBC, respectively, 69 however, there are variant forms of these 2 cholestatic diseases. 70,71 Additionally, small bile ducts are frequently the target of inflammatory attacks in these cholestatic diseases.…”

“…The risk of developing hepatocellular carcinoma is low for patients with PBC, whereas IHBC (cholangiocarcinoma) is common in PSC. [39][40][41] Moreover, we have examined the direct effect of COX-2 specific inhibitors on proliferation of BDC and GBC cell lines in vitro. These observations may provide insight into the possible potent mechanism of bile duct carcinogenesis.…”

A Nuclear Receptor Ligand Down-Regulates Cytosolic Phospholipase A2 Expression to Reduce Bile Acid?Induced Cyclooxygenase 2 Activity in Cholangiocytes: Implications of Anticarcinogenic Action of Farnesoid X Receptor Agonists

“…A recent study also showed that PGE 2 and PGF 2α irectly stimulated the proliferation of a cholangiocarcinoma cell line (5). Furthermore, it is well known that inflammatory and cholestatic conditions of the liver (e.g., PSC, biliary stone disease, and Caroli's disease) predispose patients to the development of biliary tract carcinoma (6)(7)(8)(9)(10)(11). These reports suggest that COX-2 and cytotoxic bile acids are closely related to the development of biliary tract carcinoma.…”