title: Primary sclerosing cholangitis: a clinical update.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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).
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  Recent genetic studies have revealed new risk loci, pointing to the importance of the immune system and its interaction with the biome.
  
  
  CONCLUSIONS
  On the basis of the genetic studies discussed earlier, novel agents are being developed and trialled in the treatment of PSC.
authors.affiliation: Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK Translational Gastroenterology Unit, John Radcliffe Hospital, Oxford, UK.
authors.forename: Kate D
authors.initials: KD
authors.lastname: Williamson
authors.affiliation: Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK Translational Gastroenterology Unit, John Radcliffe Hospital, Oxford, UK roger.chapman@ndm.ox.ac.uk.
authors.forename: Roger W
authors.initials: RW
authors.lastname: Chapman
mesh_terms: D015209:Cholangitis, Sclerosing / Q000175:diagnosis* / Q000453:epidemiology / Q000209:etiology / Q000628:therapy*; D004067:Digestive System Neoplasms / Q000175:diagnosis; D019693:Hepatitis, Autoimmune / Q000150:complications; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D015212:Inflammatory Bowel Diseases / Q000150:complications; D011230:Precancerous Conditions / Q000175:diagnosis; D011379:Prognosis
chemical_list: D007074:Immunoglobulin G
keywords: CCR9; cholangiocarcinoma; cholestasis; colorectal cancer; genetics; inflammatory bowel disease; primary sclerosing cholangitis; sclerosing cholangitis; ursodeoxycholic acid