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.
Keywords: CCR9; cholangiocarcinoma; cholestasis; colorectal cancer; genetics; inflammatory bowel disease; primary sclerosing cholangitis; sclerosing cholangitis; ursodeoxycholic acid.
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