Pathogenesis and clinical spectrum of primary sclerosing cholangitis

Abstract

Primary sclerosing cholangitis (PSC) is a disease of the biliary tract, which has been documented in the literature since 1867. This disease has a strong predilection for affecting men and can be seen in individuals as young as 2 years of age. PSC has a strong associated with inflammatory bowel disease, more commonly with ulcerative colitis, and is also part of the clinical spectrum of IgG4-related diseases. Small-duct PSC, a variant of PSC, also has an association with inflammatory bowel disease. The exact pathogenesis of PSC is not well understood at present, however, is likely a combination of a genetic predisposition with alteration of the molecular structure of the gut. Abnormal serum liver chemistry and presence of certain autoimmune markers are usually the first indicators leading to a diagnosis of PCS, however, these may often be normal in early stages of this disease. The diagnosis is made by cholangiography, which is now considered the gold standard. PSC is a known pre-malignant condition. Such patients have an increased risk of developing cholangiocarcinoma, gallbladder neoplasia, and colon cancer. Many new treatment modalities have emerged in the recent past, including anti-tumor necrosis factor- α and anti-integrins; however, liver transplantation is the only known cure for PSC. Despite past and present research, PSC remains an enigmatic biliary disease with few viable treatment options.

Generation of a novel mouse model for the study of autoimmune liver disease overlap syndrome

“…The first characterization of the PSC-AIH OS mouse model included the analysis of liver damage markers, such as presence of liver enzymes in the serum and the detection of autoantibodies. The typical hallmark of PSC is an elevation of AP [258]. In this study, a two to three fold elevation of AP levels in Mdr2 -/mice compared to control group was detected.…”

Cholangiocyte-Derived Exosomal lncRNA H19 Promotes Macrophage Activation and Hepatic Inflammation under Cholestatic Conditions

“…Cholestatic liver diseases, including primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC), are critical clinical problems worldwide [1][2][3]. Due to the limited understanding of their pathogenesis, the late diagnosis, and the lack of effective therapeutic options, liver transplantation remains the only solution for end-stage patients [4].…”

Small Duct Sclerosing Cholangitis: A Case Report and Review of Literature

“…CT imaging can detect thickening of the bile ducts with contrast enhancement consistent with inflammation, saccular dilatations of the intrahepatic ducts, heterogeneous bile duct dilatation, document the presence of portal hypertensive complications (i.e., varices, splenomegaly, and ascites), and can identify mass lesions [10][11][12][13][14]. Detectable auto antibodies are found in about 97% of patients with PSC [15], these auto antibodies, however, are not routinely used for the diagnosis of PSC, as they may not be present and furthermore do not correlate with disease severity or disease prognosis [16]. The classic histopathologic finding of PSC is presence of periductal concentric ("onion-skin") fibrosis, but this observation is infrequent in liver biopsy specimens from patients with PSC and may also be observed in SSC [17] (Figure 2).…”