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Primary sclerosing cholangitis: a clinical update
Kate D Williamson1, Roger W Chapman2
1Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK Translational Gastroenterology Unit, John Radcliffe Hospital, Oxford, UK.
Introduction:
Primary sclerosing cholangitis (PSC) is a progressive cholestatic disorder that ultimately can lead to cirrhosis, liver failure, malignancy and death. It is strongly associated with inflammatory bowel disease (IBD), and though a rare disease, its incidence is increasing. There are no proven medical therapies for PSC.
Sources Of Data:
Ovid Medline was utilised to search for articles with keywords 'sclerosing cholangitis' and 'cholangiocarcinoma' and containing titles 'primary sclerosing cholangitis', and references of these papers were cross-referenced for further relevant manuscripts.
Areas Of Agreement:
PSC is a rare disease, and there is a strong association with risk loci within the major histocompatibility complex and other genes common to other autoimmune diseases. PSC is a premalignant condition, associated with higher rates of hepatobiliary and colorectal cancer in patients with ulcerative colitis (UC).
Areas Of Controversy:
The pathogenesis is unclear, and competing theories exist surrounding toxic bile acids, enhanced homing of particular T cells from the gut to the liver and increased passage of toxins to the liver through a permeable bowel wall. It is unclear whether the higher rate of colonic cancer in PSC/UC occurs in PSC/Crohn's disease. Ursodeoxycholic acid therapy reduces liver enzymes but has not been shown to improve survival. It may reduce the prevalence of bowel cancer.
Growing Points:
Recent genetic studies have revealed new risk loci, pointing to the importance of the immune system and its interaction with the biome.
Areas Timely For Developing Research:
On the basis of the genetic studies discussed earlier, novel agents are being developed and trialled in the treatment of PSC.
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