Primary sclerosing cholangitis: diagnosis, prognosis, and management

Abstract

Primary sclerosing cholangitis (PSC) is a chronic immune-mediated disease of the liver of unclear etiology, characterized by chronic inflammation and fibrosis of bile ducts. It primarily affects middle-aged men and is associated with 4-fold increased mortality as compared with an age- and sex-matched population. Progressive biliary and hepatic damage results in portal hypertension and hepatic failure in a significant majority of patients over a 10- to 15-year period from the initial diagnosis. In addition, PSC confers a markedly increased risk of hepatobiliary cancer, including cholangiocarcinoma and gallbladder cancer, as compared with the general population, and cancer is the leading cause of mortality in patients with PSC. It is associated with inflammatory bowel disease in 70% of patients and increases the risk of colorectal cancer almost 10-fold. Despite significant research efforts in this field, the pathogenic mechanisms of PSC are still incompletely understood, although growing evidence supports the role of genetic and immunologic factors. There are no proven medical therapies that alter the natural course of the disease. Thus, liver transplantation is the only available treatment for patients with advanced PSC, with excellent outcomes in this population.

Keywords: AIH; CA19-9; CCA; CRC; ERCP; FISH; IBD; LT; MRCP; PSC; Primary sclerosing cholangitis (PSC); UC; UDCA; autoimmune hepatitis; carbohydrate antigen 19-9; cholangiocarcinoma; colorectal cancer; endoscopic retrograde cholangiopancreatography; fluorescence in situ hybridization; inflammatory bowel disease; liver transplantation; magnetic resonance cholangiopancreatography; primary sclerosing cholangitis; ulcerative colitis; ursodeoxycholic acid.

Figure 1

Typical cholangiographic findings of primary sclerosing cholangitis. (a) MRCP demonstrating multiple strictures and dilatations of the biliary tree, affecting the intrahepatic and extrahepatic biliary tree; (b) ERCP with typical findings of pruning and beaded appearance of the biliary tree.

Figure 2

A. Classic ‘onion skin’ fibrosis, causing obliteration of the bile ducts in primary sclerosing cholangitis [Photograph courtesy: Thomas Smyrk, M.D., Department of Pathology, Mayo Clinic, Rochester] B. Ductopenia, without onion-skinning fibrosis in small-duct primary sclerosing cholangitis [Photograph courtesy: Thomas Smyrk, M.D., Department of Pathology, Mayo Clinic, Rochester]

Figure 2

A. Classic ‘onion skin’ fibrosis, causing obliteration of the bile ducts in primary sclerosing cholangitis [Photograph courtesy: Thomas Smyrk, M.D., Department of Pathology, Mayo Clinic, Rochester] B. Ductopenia, without onion-skinning fibrosis in small-duct primary sclerosing cholangitis [Photograph courtesy: Thomas Smyrk, M.D., Department of Pathology, Mayo Clinic, Rochester]